Journal of Pathology and Translational Medicine

Original Articles

The Usefulness of Immunocytochemistry of CD56 in Determining Malignancy from Indeterminate Thyroid Fine-Needle Aspiration Cytology: Hyunseo Cha, Ju Yeon Pyo, Soon Won Hong; J Pathol Transl Med. 2018;52(6):404-410. Published online October 15, 2018; DOI: https://doi.org/10.4132/jptm.2018.09.20

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Background
Fine-needle aspiration cytology serves as a safe, economical tool in evaluating thyroid nodules. However, about 30% of the samples are categorized as indeterminate. Hence, many immunocytochemistry markers have been studied, but there has not been a single outstanding marker. We studied the efficacy of CD56 with human bone marrow endothelial cell marker-1 (HBME-1) in diagnosis in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) category III.
Methods
We reviewed ThinPrep liquid-based cytology (LBC) samples with Papanicolaou stain from July 1 to December 31, 2016 (2,195 cases) and selected TBSRTC category III cases (n = 363). Twenty-six cases were histologically confirmed as benign (six cases, 23%) or malignant (20 cases, 77%); we stained 26 LBC slides with HBME-1 and CD56 through the cell transfer method. For evaluation of reactivity of immunocytochemistry, we chose atypical follicular cell clusters.
Results
CD56 was not reactive in 18 of 20 cases (90%) of malignant nodules and showed cytoplasmic positivity in five of six cases (83%) of benign nodules. CD56 showed high sensitivity (90.0%) and relatively low specificity (83.3%) in detecting malignancy (p = .004). HBME-1 was reactive in 17 of 20 cases (85%) of malignant nodules and was not reactive in five of six cases (83%) of benign nodules. HBME-1 showed slightly lower sensitivity (85.0%) than CD56. The specificity in detecting malignancy by HBME-1 was similar to that of CD56 (83.3%, p = .008). CD56 and HBME-1 tests combined showed lower sensitivity (75.0% vs 90%) and higher specificity (93.8% vs 83.3%) in detecting malignancy compared to using CD56 alone.
Conclusions
Using CD56 alone showed relatively low specificity despite high sensitivity for detecting malignancy. Combining CD56 with HBME-1 could increase the specificity. Thus, we suggest that CD56 could be a useful preoperative marker for differential diagnosis of TBSRTC category III samples.

Citations

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The Effects of Immunocytochemistry on Diagnostic Accuracy in Thyroid Fine Needle Aspiration Cytology: A Retrospective Study
Ali Mızrak, Cansu Benli Işık, Esen Gül Uzuner, Saime Gül Barut
Clinical and Experimental Health Sciences.2025; 15(3): 531. CrossRef
Preoperative evaluation of thyroid nodules – Diagnosis and management strategies
Tapoi Dana Antonia, Lambrescu Ioana Maria, Gheorghisan-Galateanu Ancuta-Augustina
Pathology - Research and Practice.2023; 246: 154516. CrossRef
Immunocytochemistry in thyroid cytology and its multiple roles: a systematic review
Federica Policardo, Pietro Tralongo, Angela Feraco, Federica Vegni, Angela Carlino, Alfredo Pontecorvi, Celestino Pio Lombardi, Marco Raffaelli, Francesco Pierconti, Luigi Maria Larocca, Esther Diana Rossi
Diagnostic Histopathology.2023; 29(8): 386. CrossRef
Paving the path toward multi-omics approaches in the diagnostic challenges faced in thyroid pathology
Isabella Piga, Vincenzo L’Imperio, Giulia Capitoli, Vanna Denti, Andrew Smith, Fulvio Magni, Fabio Pagni
Expert Review of Proteomics.2023; 20(12): 419. CrossRef
CD56 Expression in Papillary Thyroid Carcinoma Is Highly Dependent on the Histologic Subtype: A Potential Diagnostic Pitfall
Uiju Cho, Yourha Kim, Sora Jeon, Chan Kwon Jung
Applied Immunohistochemistry & Molecular Morphology.2022; 30(5): 389. CrossRef

The Diagnostic Usefulness of HMGA2, Survivin, CEACAM6, and SFN/14-3-3 δ in Follicular Thyroid Carcinoma: Min Hye Jang, Kyeong Cheon Jung, Hye Sook Min; J Pathol Transl Med. 2015;49(2):112-117. Published online March 12, 2015; DOI: https://doi.org/10.4132/jptm.2015.01.31

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Abstract PDF

Background
Follicular thyroid carcinoma (FTC) is the second most common thyroid malignancy and its differential diagnosis includes follicular adenoma (FA) and adenomatous goiter (AG). Several ancillary markers have been suggested to aid in the diagnosis of FTC, but the successful use of these methods still needs to be validated. Methods: In the present study, we verified the immunoexpression of HMGA2, CEACAM6, survivin, and SFN/14-3-3 δ in lesions including 41 AGs, 72 FAs, and 79 FTCs. We evaluated their diagnostic usefulness, combined with galectin 3, Hector Battifora mesothelial 1 (HBME1), cytokeratin 19, and cyclin D1, in diagnosing FTC. Results: The expressions of HBME1 (65.8%) and HMGA2 (55.7%) were significantly higher in FTCs than in FAs and AGs (p<.001 and p=.005, respectively). HBME1 was the only marker that was more frequently expressed in FTCs than in FAs (p=.021) and it was more frequently expressed in follicular neoplasms than in AGs (p<.001). Among the novel markers, the combination of HMGA2 and HBME1 showed the highest sensitivity (72.2%) and specificity (76.1%) for diagnosing FTC. CEACAM6, survivin, and SFN/14-3-3 δ were barely expressed in most cases. Conclusions: Our present results show that only HMGA2 can be beneficial in differentiating FTC using the novel markers.

Citations

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High mobility group protein 2 (HMGA2) is highly expressed in a broad range of benign and malignant tumors
Viktoria Chirico, Fatih Baybars Ergüven, Katharina Möller, Florian Lutz, Florian Viehweger, Martina Kluth, Claudia Hube-Magg, Christian Bernreuther, Guido Sauter, Andreas H. Marx, Ronald Simon, Frank Jacobsen, Patrick Lebok, Till S. Clauditz, Waldemar Wil
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Assessing the potential of high-mobility group AT-hook 2 immunohistochemical staining as a prognostic marker of metastatic recurrence in follicular thyroid cancer: a retrospective cohort study
Yuka Ito, Junko Sakumoto, Hideki Hirabayashi, Shinichi Haruna, Wataru Konno, Itsuo Nakajima, Kazuyuki Ishida, Yasuo Haruyama, Toshimi Sairenchi, Eijun Nishihara, Shuji Fukata, Akira Hishinuma, Takahiko Kogai
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HMGA2 promotes nasopharyngeal carcinoma progression and is associated with tumor resistance and poor prognosis
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miR‐98‐5p promotes apoptosis and inhibits migration and cell growth in papillary thyroid carcinoma through Bax/Caspase‐3 by HMGA2
Kai Qiu, QingJi Xie, Shan Jiang, Ting Lin
Journal of Clinical Laboratory Analysis.2020;[Epub] CrossRef
High mobility group A protein-2 as a tumor cancer diagnostic and prognostic marker: a systematic review and meta-analysis
Yen Thi-Hai Pham, Ovie Utuama, Claire E. Thomas, Jong A. Park, Carlo La Vecchia, Harvey A. Risch, Chi Thi-Du Tran, Thanh V. Le, Paolo Boffetta, Leon Raskin, Hung N. Luu
European Journal of Cancer Prevention.2020; 29(6): 565. CrossRef
Diagnostic performance of HMGA2 gene expression for differentiation of malignant thyroid nodules: A systematic review and meta‐analysis
Bo Hyun Kim, Seong Jang Kim, Mijin Kim, Sang‐Woo Lee, Shin Young Jeong, Kyoungjune Pak, Keunyoung Kim, In Joo Kim
Clinical Endocrinology.2018; 89(6): 856. CrossRef
Thyroid follicular adenomas and carcinomas: molecular profiling provides evidence for a continuous evolution
Geneviève Dom, Sandra Frank, Sebastien Floor, Pashalina Kehagias, Frederick Libert, Catherine Hoang, Guy Andry, Alex Spinette, Ligia Craciun, Nicolas de Saint Aubin, Christophe Tresallet, Frederique Tissier, Frederique Savagner, Samira Majjaj, Ilse Gutier
Oncotarget.2018; 9(12): 10343. CrossRef
APLP2, RRM2, and PRC1: New Putative Markers for the Differential Diagnosis of Thyroid Follicular Lesions
Esmeralda Castelblanco, Carles Zafon, Javier Maravall, Pilar Gallel, Montserrat Martinez, Ismael Capel, Maria Rosa Bella, Irene Halperin, Jordi Temprana, Carmela Iglesias, Manel Puig-Domingo, Mercedes Robledo, Xavier Matias-Guiu, Didac Mauricio
Thyroid.2017; 27(1): 59. CrossRef
Prognostic implication of histological features associated with EHD2 expression in papillary thyroid carcinoma
Yourha Kim, Min-Hee Kim, Sora Jeon, Jeeyoon Kim, Chankyung Kim, Ja Seong Bae, Chan Kwon Jung, Yves St-Pierre
PLOS ONE.2017; 12(3): e0174737. CrossRef
Survivin DEx3 as a biomarker of thyroid cancers: A study at the mRNA and protein level
Joanna Waligórska-Stachura, Nadia Sawicka-Gutaj, Maciej Zabel, Mirosław Andrusiewicz, Paweł Gut, Agata Czarnywojtek, Marek Ruchała
Oncology Letters.2017; 13(4): 2437. CrossRef
High-Frequency Ultrasound-Guided Injection for the Generation of a Novel Orthotopic Mouse Model of Human Thyroid Carcinoma
Adelaide Greco, Sandra Albanese, Luigi Auletta, Peppino Mirabelli, Antonella Zannetti, Crescenzo D'Alterio, Gennaro Di Maro, Francesca Maria Orlandella, Giuliana Salvatore, Andrea Soricelli, Marco Salvatore
Thyroid.2016; 26(4): 552. CrossRef
The study of galectin-3, Ki-67, ubiquitin, HMGA-2 by polymerase chain reaction in real time (RT-PCR) in the puncture specimens of nodular goiter
Irina S. Berjozkina, Tat'jana V. Saprina, Anastasija P. Zima, Anna V. Isaeva, Venera N. Latipova, Marat R. Muhamedov, Leonid R. Bazilevich, Oleg S. Popov, Dar'ja A. Skuratovskaja, Kristina A. Jurova, Larisa C. Litvinova
Clinical and experimental thyroidology.2016; 12(2): 19. CrossRef
High-mobility group A2 overexpression is an unfavorable prognostic biomarker for nasopharyngeal carcinoma patients
Zhuoxing Liu, Kunpeng Wu, Zhixiong Yang, Aibing Wu
Molecular and Cellular Biochemistry.2015; 409(1-2): 155. CrossRef
Defining the value of CD56, CK19, Galectin 3 and HBME-1 in diagnosis of follicular cell derived lesions of thyroid with systematic review of literature
Duško Dunđerović, Jasmina Marković Lipkovski, Ivan Boričic, Ivan Soldatović, Vesna Božic, Dubravka Cvejić, Svetislav Tatić
Diagnostic Pathology.2015;[Epub] CrossRef

Brief Case Report

Papillary Cystadenoma of the Fallopian Tube Not Associated with von Hippel-Lindau Disease: A Case Report: Jae Yeon Seok, Myunghee Kang, Jungsuk An, Hyunchul Kim, Kwang-Beom Lee, Hyun Yee Cho; Korean J Pathol. 2014;48(5):382-386. Published online October 27, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.5.382

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A Retrospective Study on the Occurrence and Prevalence of Ovarian Masses in the Patients of Rajkot District, Gujarat
Kirtan M Vyas, Avni P Patel, Ashita K Vyas, Hardik Gohel
Journal of the Scientific Society.2023; 50(3): 375. CrossRef
Clear Cell Papillary Cystadenoma of the Ovary Masquerading as Metastatic Clear Cell Renal Cell Carcinoma: A Case Report and Review of the Literature
Aarti E. Sharma, Farid Saei Hamedani, Julieta E. Barroeta, Peter Pytel, Jennifer A. Bennett, Ricardo R. Lastra
International Journal of Gynecological Pathology.2021; 40(3): 290. CrossRef
Mesonephric (Wolffian) Pseudoendometrioid Carcinoma of the Broad Ligament, Arising From a Papillary Cystadenoma
Philippe Moerman, Frederic Amant, Ignace Vergote
International Journal of Surgical Pathology.2016; 24(7): 635. CrossRef

Original Articles

Application of Immunohistochemical Technique in the Cytologic Diagnosis of herpes Simplex Virus Infection.: Hye Rim Park, Kap No Lee, Seung Young Paik; J Pathol Transl Med. 1990;1(1):74-84.

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Abstract PDF: Herpes simplex virus type 1 and 2(HSV-1, HSV-2) are the ubiquitous human pathogens responsible for a variety of afflictions, HSV-2 is one of the viruses that were suspected of promoting carcinogenesis in the uterine cervix. Certainly, there is a need for the more sensitive and accurate laboratory techniques for HSV detection. We examined total 80 cases of smears including 17 Tzanck smears of skin and 63 cases of Papanicolaou smears from total 77 patients with clinical impression of herpetic infections, from September, 1985 through August, 1989. Immunohistochemical typings for HSV-1 and HSV-2 were performed together with routine cytologic findings and compared The results are as follows : 1) patients were 9 males and 33 females, and age distribution was between 5 and 71 years 2) Subjective symptoms such as ulceration, vesicle, vaginal discharge, pruritus, and pain were complained in 36 patients and 38 cases were genital herpes. Recurrence was noted in 11 cases. 3) Positive results were obtained in 42 among 80 cases. 4) Both routine cytology and imunohistochemical staining were positive in 13 cases and in 24 cases only immunohistochemical staining were positive. 5 cases were positive only in routine cytologic smears. 5) The cases that immunocytochemical stain had been performed were 37 cases, which were all positive in type 2, Among the above 37 cases, type 1 also were positive in 5 cases. The results show that the immunoperoxidase technique is one of the rapid and reliable method to confirm the herpetic infection when suspected and that it is particularly useful when the Papanicolaou smear findings are equivocal

Ultrastructural and Immunohistochemical Investigations of Exocrine and Endocrine Cells in Fetal Human Pancreas.: Jung Ran Kim, Je G Chi, Jung Hee Cho; Korean J Pathol. 1995;29(3):286-295.

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Abstract PDF: The pancreas consists of two types of tissue arising from same primitive cells, but with entirely different functions. Although the adult human pancreas and fetal islet tissue have been the subject of numerous electron microscopic studies, little is known of the ultrastructure of the developing human exocrine pancreas. The purpose of the current study is to investigate development of endo and exocrine of pancreas, especially during the middle trimester of human fetal life, which is the period of acinar cell maturation. Fresh autopsy specimens of pancreas, taken from 15 human fetuses at the 12th (n=2), 13-16th (n=5), 17-20th (n=4), 21-24th (n=2) and 25-28th (n=2) weeks of gestation, were studied electron microscopically, and immunohistochemically. Antisera against insulin, somatostatin, glucagon, pancreatic polypeptide and gastrin, were used for immunohistochemistry. By the 12th week, primitive exocrine acini were identified and these were matured rapidly in the next 6 weeks. At the 17th week stage, ultrastructural examination revealed atypical zymogen granules in the acinar cells. These became progressively less numerous in the 21-28 week period when classical zymogen granules increased upto the level of adult stage. All the endocrine cells were found at the 12th week, forming primitive or mature islets. The relative ratio of endocrine cells at the 12th week was about 35.4%, 24.9%, 39.8%, 0.5% for A, B, D & PP cell, respectively. But at the 25th to 28th week of development, the relative numbers of A and D cells decreased somewhat, whereas those of the B cells increased. The PP cells were constant. The G cells were found at the 12th week of fetal period, which appeared through out the on period.

Histopathologic Re-evaluation of Thymoma with Immunonhistochemical Study for bcl-2 and MIC-2 Protein.: Kyung Moo Yang, Mee Yon Cho, Soon Won Hong, Tae Seung Kim, Chan Il Park, Woo Ick Yang; Korean J Pathol. 1997;31(5):446-461.

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Abstract PDF: We reviewed 86 thymic epithelial tumors and reclassified them according to the Kirchner and Muller- Hermelink classification. They were subtyped as medullary, mixed, predominantly cortical (organoid), cortical, well differentiated thymic carcinoma, and poorly differentiated thymic carcinoma. The frequency of each subtype was determined and histologic findings were related to stage and myasthenia gravis. Immunohistochemical stains for bcl-2 protein as a marker for medullary thymocytes and MIC-2 protein as a marker for cortical thymocytes were performed in each case. The stages and association of myasthenia gravis was significantly different in each subtypes. The results of this study demonstrate that this histogenetic classification is clinically applicable. The bcl-2 protein was specifically demonstrated in lymphocytes within areas of medullary differentiation and MIC-2 protein in cortical differentiation. The expression of bcl-2 and MIC-2 proteins lend histogenetic support for this new classification of thymoma. Bcl-2 protein is strongly expressed in tumor epithelial cells of every case of poorly differentiated thymic carcinoma whereas the other types of thymic epithelial tumors do not show epithelial expression of this protein. The strong expression of bcl-2 protein in tumor epithelium may be considered as a predictor of aggressive behavior in thymic epithelial tumors.

Nature of Stromal Cells in Cerebellar Capillary Hemangioblastoma: Immunohistochemical analysis.: Soon Won Hong, Tai Seung Kim, Ji Young Han; Korean J Pathol. 1995;29(5):584-589.

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Abstract: The origin of the stromal cell of cerebellar hemangioblastoma has long been studied electron microscopically and immunohistochemically. The results and theories about the stromal cell origin are variable and plentiful. However, the exact origin of the stromal cell remains controversial. The present study is aimed to elucidate the nature of the stromal cell of cerebellar hemangioblastoma. Ten cases of hemangioblastoma in Severance Hospital were used for immunohistochemical analysis of the stromal cell. The immunohistochemical staining of GFAP, S-100 protein, NSE, alpha-l-antichymottypsin, cytokeratin, CD 68, factor VIII related antigen, and synaptophysin were performed. The results were as follows; GFAP and S-100 protein were stained mainly but weakly in bellar capillary spindle cell and cellular process. NSE was stained mainly in foam cells, and 6 cases among them revealed strong reaction. ct-l-antichymotrypsin was stained in a few foam cells of 5 cases. Cytokeratin, CD 68, factor VIII related antigen, and synaptophysin showed negative reaction. Based on these results, it is considered that the origin of the stromal cell is histiocytic or neurogenic rather than glial. The weak positivity of GFAP and S-100 protein may support the neurogeriic origin but ct-l-antichymotrypsin positivity does not support the possibility. The positivity of GAP and S-100 protein supports the phagocytic action of histiocytic cell and suggests histiocytic origin rather than neurogenic.

Comparative Assessment of Immunohistochemical and Zieh1-Neelsen Stains for Demonstration of Mycobacterium Tuberculosis.: Mee Yon Cho, Soon Hee Jung, Woo Ick Yang; Korean J Pathol. 1993;27(3):243-248.

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Abstract PDF: To obtain a useful method for the identification of mycobacteria in tissue section, we evaluated 118 cases of tuberculosis: 48 pulm onary, 14 lymph nodal and 56 synovial tuberculosis. Seventy nine of these cases underwent the culture study. Sections stained with anti-Mycobacterium bovis were compared with the results of the Zieh1-Neelsen stain and culture. The immunohistochemical stain for Mycobacterium bovis in al examined cases was not any more sensitive than the Zieh1-Neelsen stain(p>0.05). Neverthless, the immunohistochemical stain was a useful method for the localization of mycobacteria because of the striking contrast between its background and the wider dimension of a positive area. Immunoreactive areas demonstrated a few intact mycobacteria showing a positive reaction in the Zieh1-Neelsen stain. In conclusion, double staining method using the immunohischemical stain for Mycobacterium bovis and the Zieh1-Neelsen stain is an efficient technique in oder to confirm the diagnosis of tuberculosis.

Case Report

Interfollicular Hodgkin's Lymphoma: A case report.: Lee So Maeng, Kyung Mee Kim, You Mee Kang, Chang Seok Kang, Sang In Shim; Korean J Pathol. 1995;29(6):804-806.

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Abstract PDF: An unusual pattern of focal involvement of lymph nodes by Hodgkin's disease is described using the name Interfollicular Hodgkin's Disease. It is characterized by florid reactive follicular hyperplasia which overshadows involvement of the interfollicular zones by Hodgkin's desease. The importance of interfollicular Hodgkin's disease rests on its misdiagnosis as a benign lesion. We report a case of interfollicular Hodgkin's disease in a 34-year-old female patient in the inguinal area. The lymph nodes showed reactive follicular hyperplasia. The focal interfollicular spaces were invaded by Hodgkin's disease. The Reed-Stemberg cells stained positively with CD15 and CD30 antibody in the immunohistochemical stain. An in situ hybridization study looking for EBV was negative in these R-S cells.

Original Articles

p53 Protein Expression in Infiltrating Ductal Carcinoma of the Breast.: Soon Hee Jung, Mee Yon Cho, Soo Yong Kim; Korean J Pathol. 1996;30(1):7-14.

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Abstract PDF: Overexpression of the nuclear phosphoprotein p53 is the most common genetic anomaly found in primary human cancer and mutation of the tumor suppressor gene p53 has been identified in breast cancer cell lines. In this study, we evaluated the prognostic significance of p53 protein expression in patients with mammary infiltrating ductal carcinoma and its correlation with histopathologic grade, lymph node status, tumor size, p53 protein expression and survival. Among 53 cases, p53 protein expression was detected in 26(49.1%) cases by immunohistochemistry. There was no correlation between p53 protein overexpression and histopathologic grade(p=0.09) or lymph node status(p=0.38) and between survival and histopathologic grade (p=0.68) or lymph node status(p=0.52). However, p53 protein expression was significantly correlated with survival(p=0.01) and patients with p53 protein-positive tumors showed poorer survival times. But Cox multivariate analysis showed the lymph node status is significant(p=0.01). The authors conclude that the presence of mutant p53 protein and lymph node status may serve a prognostic role, in a subset of mammary infiltrating ductal carcinoma cases.

Histopathologic and Immunohistochemical observation on Malignant Schwannoma.: Tae Sook Hwang, Seong Hoe Park, Eui Keun Ham; Korean J Pathol. 1990;24(4):446-455.

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Abstract PDF: Histopathologic and immunohistochemical analysis using antibodies for S-100 protein and keratin has been conducted on 21 cases of malignant schwannomas. The 21 cases were divided into the following three groups Group A: tumors originating from the nerve trunk or neurofibroma; Group B: tumors related to von Recklinghausen's disease; and Group C: other tumors not belonging to the above groups but histologically diagnosed as malignant schwannoma. The commonest histological pattern consisted of either closely packed or loosely arranged interlacing fascicles of slender spindle cells with wavy fibrillar cytoplasm, followed by myxoid change, perithelial pattern, hyaline change of the blood vessels, and hyalinlzed cords or nodules. Nine out of 12 cases of malignant schwannomas in group A and B, and 7 out of 9 cases of group C were positive for S-100 protein. None of the above cases showed positive staining reaction for keratin. Since 7 of 9 malignant schwannomas in Group C stained with S-100 protein, we can conclude that careful histological analysis supplemented by immunohistichemical study can make a conclusive diagnosis in most of the cases of malignant schwannomas even in cases that do not fulfil the traditional strict criteria.

Immunohistochemical Study of the Expression of the p53 Protein in Primary Lung Cancer.: Sang Yong Lee, Jin Sook Jeong, Sook Hee Hong; Korean J Pathol. 1996;30(3):218-227.

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Abstract PDF: An immunohistochemical stain for p53 tumor suppressor gene product was performed in 59 primary lung cancers to study the relation between its expression and type of the tumor, degree of tumor differentiation,clinical stage and smoking. The results were as follows: 1. The expression of mutant p53 protein was noted in 28 of 59 cases(47.5%) of primary lung cancers. The p53 protein was expressed in 21 of 35(60%) squamous cell carcinomas, in 6 of 21(28.6%) adenocarcinomas, and 1 of 1(100%) small cell carcinoma. There was a significant difference in expression of p53 among the different histologic types of lung cancer(p<0.05). 2. The incidence of p53 protein expression did not correlate with the degree of tumor cell differentiation or the clinical stage of lung carcinoma(p>0.05). 3. The incidence of p53 protein expression was higher in smokers(current: 75%, former: 46.2%) than in non-smokers(5.6%) and was increased in direct proportion to the pack years. There was a statistically significant correlation between p53 expression and smoking(p<0.05). The mutation of p53 gene may often be an early event in the development of lung cancer and it is suggested that the smoking known as a risk factor for the development of the lung cancer may be associated with the transformation of p53 tumor suppressor gene into mutant p53 gene or oncogene.

Application of Immunohistochemical Stain for Granulocytic Sarcoma.: Yeong Ju Woo, Chan Hwan Kim, Jong Eun Joo; Korean J Pathol. 1994;28(1):30-37.

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Abstract PDF: Granulocytic sarcoma is a rare localized tumor composed of granulocytic precusor cells. Granu-locytic sarcoma occurs in a variety of clinical conditions and it is often misdiagnosed histologically. Differential diagnosis frorh lymphoma or nonhematopoietic malignancies such as undifferentiated carcinoma or sarcoma is difficult in the routing histologic examination. An evaluation of clinical and histopathologic features was done on 4 cases of granulocytic sarcoma which were diagnosed at Pusan Paik Hospital from 1988 to 1992. During the period, 282 cases of myelogenous leukemia were diagnosed. Immunohistochemical reaction for lysozyme, myelopero-xidase, leukocyte common antigen, epthelial membrane antigen and cytokeratin was assessed comparing to lymphoma and undifferentiated carcinoma. The histologic features of the granulocytic sarcoma revealed thin nuclear membrane, fine chromatin pattern and one or two small nucleoli. It also often involved the vascular wall and infiltrated the native structures without destruction. Immunohistochemical stain revealed that all(4 cases) of granulocytic sarcoma showed diffuse and strong positivity for myeloperoxidase, and partial but strong positivity for lysozyme. One case of granulocytic sarcoma was negative and 3 cases revealed focal positive reaction for LCA, and all 4 cases was negative for cytokeratin and EMA. In summary, careful observation under light microscopy with immunohistochemical stain for myeloperoxidase, lysozyme, and LCA is helpful in the differential diagnosis of granulocytic sarcoma from malignant lymphoma and cytokeratin and EMA is useful for differential diagnosis from undifferentiated carcinoma.

Immunohistochemical Study of Primary Large Cell Undifferentiated Carcinoma of the Lung.: Hye Seung Han, Jeong Wook Seo, Eui Keun Ham; Korean J Pathol. 1996;30(5):417-426.

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Abstract PDF: We performed a histopathologic and immunohistochemical study of 23 cases of surgically resected large cell undifferentiated carcinoma(LCUC) of the lung. The relative incidence of LCUC was 7.6% among the total resected cases of primary lung cancer over 7 years(1987-1993). The mean age of the patients was 56 years and 21 cases were male. The mean size of the mass was 5 cm and 11 cases were located peripherally. According to the histologic features, LCUC could be divided into three groups: squamous cell carcinoma-like(6 cases), adenocarcinoma-like(13 cases), and small cell carcinoma-like(4 cases) groups. The histologic differences were related to the variations of the immunohistochemical properties, but there were no differences in prognosis among these groups. Immunoreactivity to cytokeratin(CAM 5.2) was demonstrated in 22/23(96%). Carcinoembryonic antigen was positive in 13/23(57%). Neuron specific enolase and chromogranin were positive in 11/23(48%) and 5/23(22%), respectively. Vimentin was seen in 11/23(48%). From these observations, we could subclassify them by their immunologic phenotypes; exocrine features in 6/23(26%), neuroendocrine(NE) features in 4/23(17%), both exocrine and NE phenotypes in 7/23(30%), and 6 cases(26%) showed neither phenotype. The group with NE features showed a worse prognosis(P<0.05) and immunoreactivity for vimentin was also related to a worse prognosis(P<0.05). These findings imply that the immunohistochemical properties of LCUC are closely related to the histopathologic features. The groups, subdivided by histology and immunoreactivity, showed no prognostic difference except for the NE differentiation and reaction for vimentin.

Detection of HBV DNA in Needle Biopsied Paraffin Embedded Liver Tissues of Chronic Hepatitis B Patients by PCR: Comparison with Serological and Immunohistochemical Studies.: Hye Soo Lee, Kahng Yeul Oh, Joo Heon Kim, Yoon Jeong Kim, Sam Im Choi, Dong Geun Lee, Sang Ho Kim; Korean J Pathol. 1996;30(6):495-504.

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Abstract PDF: In this study, the prevalence of Hepatitis B virus(HBV) DNA in the needle biopsied paraffin embedded liver tissues of chronic hepatitis B patients by rapid nested PCR was examined. DNA was extracted by NaOH with boiling, and amplified by rapid air thermocycler with glass capillary tubes and nested PCR with two primer sets specific for the surface and the core genes of HBV. The PCR results were compared to that of serum HBeAg, serum HBV DNA by dot blot hybridization with a radioactive DNA probe, and tissue immunohistochemical (HBsAg/ HBcAg) studies. Among 44 patients with chronic hepatitis with serum HBsAg positivity, HBV DNA could be detected by PCR in 43 liver tissues (98%). This results were comparable to the positive rates of 94%(31/33) for serum HBV DNA, 80%(35/44) for serum HBeAg, and 59%(26/44) and 75%(33/44) for tissue HBsAg and HBcAg, respectively. The accordance rate between tissue PCR and serum DNA probe testing was 91%. The results indicate that HBV DNA detection by rapid nested PCR of paraffin embedded liver tissues by needle biopsy is a more sensitive method to detect the HBV DNA carrier than the serum HBeAg or tissue HBsAg/HBcAg status, and is well correlated with the result of serum HBV DNA probe testing. Therefore this method is a practical indicator for the diagnosis and replication status in retrospective analysis.

An Immunohistochemical Study on the Distribution of Endotoxin.: Tae In Park, Jung Ja Park, Jyung Sik Kwak, In Soo Suh; Korean J Pathol. 1994;28(3):260-271.

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Abstract: This study was performed to investigate the distribution of endotoxin in various organs after intraperitoneal injection of E. coli homogenator(0111:B4, 3X10(9)cells/200g of body weight). Sprague-Dawley rats were intraperitoneally injected with E. coli homogenator and sacrificed 1 and 3 hours after injection. The lung, liver, and kidney were immunohistochemically stained with avidin-biotin complex method and observed by light and electron microscopy. On the light microscopy, granular deposits of reaction products of immunohistochemical stain were found on the cytoplasmic membrane of endothelial cells and some of parenchymal cells of all organs observed. Electron microscopic study revealed finely granular reaction products on the surface of endothelial cells and some of parenchymal cells. The pinocytotic vesicles of endothelial cells demonstrated reaction products in the early phase of experiment. The distribution of reaction products were prominent in the liver among three organs. The Kupffer cells showed the most sensitive and strongest positive reaction. The hepatocytes and endothelial cells revealed weak positive reaction 3 hours later. The alveolar macrophages of the lung were also positive from the early phase of endotoxemia, while the pneumocytes and alveolar septa demonstrated weakly positive reaction in the later phase. The capillary endothelium of the kidney revealed positive reaction from the early phase. According to above results, it is concluded that the endotoxin entered into the systemic circulation was captured in the liver and lung. And both mononuclear phagocytic system and endothelial cells could be activated or damaged by endotoxin.

A Study of beta 2-Microglobulin Expression in Uterine Cervical Epithelial Lesion.: Na Hye Myong, Eui Keun Ham; Korean J Pathol. 1991;25(5):436-445.

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Abstract: Beta-2-microglubulin(beta 2m), the invariable light chain of the histocompatibility antigen is present on the surfaces of most human nucleated cells. It has proved to be reduced or disappeared on the cell surfaces of variable skin cancers. Patterns of beta 2m stainability in normal uterus and of the loss in several cervical epithelial lesions were examined by immunohistochemical staining using rat monoclonal and rabbit polyclonal anti-beta 2m, repectively on fresh tissues of 13 cases and formalin-fixed paraffin-embedded tissues of 23 cases. To know patterns of loss of beta 2m stainability and measure its extent and degree, only fixed tissues were examined. Fresh uterine tissue showed beta 2m stainability present on the cell membranes of squamous epithelium, endocervical gland, and capillary endothelium. Of these, squamous epithelium of uterine cervix revealed most characteristic lace-like staining along the cell outlines. Paraffin-embedded 23 cases were classified as group I (6 normal conrol and metaplasia), II (5 mild and moderate dysplasia), III (6 severe dysplasia and carcinome in situ), and IV ( 6 microinvasive and invasive squamous cell carcinoma). Group 2-4 showed reduced beta 2m stainability when compared to group 1 that exhibited the similar stainability as fresh normal cervical epithelium. The reduction or less proved to be statistically significant(p-value<0.001) in group 3 and 4 except for group 2. In spite of being invasive cases, a few disclosed beta 2m positive cells mainly in well-differentiated areas. In sum, ABC immunohistochemical staining of beta 2m showed the tendency tend to decrease or disappear in uterine cervical epithelial lesions with premalignant or malignant change and rather to appear in some well-differentiated areas of malignant lesions.

Case Report

Adenoid Basal Carcinoma Associated with Invasive Squamous Cell Carcinoma of Uterine Cervix: A case report.: Hyun Jung Kim, Dong Won Kim, So Young Jin, Dong Wha Lee; Korean J Pathol. 1996;30(8):739-741.

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Abstract PDF: Adenoid basal carcinoma of the uterine cervix is a rare neoplasm that accounts for less than 1% of cervical adenocarcinomas. Though it has been confused with adenoid cystic carcinoma, it is now distinctly recognized by better prognosis and different histologic and immunohistochemical findings. We have experienced a case of adenoid basal carcinoma associated with invasive squamous cell carcinoma of the uterine cervix in a 52-year-old woman. The tumor was composed of small, round to oval nests of basaloid cells with peripheral palisading. Some of the nests showed central cystic spaces, or cribriform pattern, and central squamous differentiation with cytological atypia. Invasive squamous cell carcinoma was located adjacent to the adenoid basal carcinoma without any transition between these two lesions. Immunohistochemically, the tumor cells disclosed positive staining for cytokeratin, but negative reaction for CEA, EMA, and S-100 protein.

Original Articles

Immunohistochemical Application of Leukocyte Common Antigen and Epithelial Membrane Antigen in the Diagnosis of Large Cell Undifferentiated Tumors.: Chan Hwan Kim, Sang Sook Lee, Chai Hong Chung; Korean J Pathol. 1988;22(3):215-221.

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Abstract PDF: A total of 42 cases undifferentiated large cell tumors were stained by immunoperoxidase techniques using antibodies against leukocyte common antigen (LCA) and epithelial membrane antigen (EMA). In 18 of the 21 cases studied, initially diagnosed as malignant lymphoma or Hodgkin's disease, reactivity with monoclonal anti-LCA (and noreactivity with monoclonal anti-EMA)indicated that the tumor was a lymphomas. The remaining 3 cases gave the reverse reaction pattern and therefore were classified as carcinoma. One out of 16 cases diagnosed as undifferentiated carcinoma proved to be a case of mialignant lymphoma in 5 patients in whom the original diagnosis was uncertain, a definite diagnosis was possible in all cases and 3 of these proved to be large cell lymphoma; the remainders, undifferentiated carcinoma. It is suggested that the staining of undifferentiated human neoplasms using combinations of antibodies reactive with epithelial and lymphoid cells may result in much greater diagnostic accuracy.

Detection of Helicobacter pylori in Gastric and Duodenal Biopsy Specimens by Immunohistochemical Stain.: Jong Im Lee, Jung Ran Kim, Jung Ho Lee, Gyoung Yim Ha; Korean J Pathol. 1996;30(10):873-885.

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Abstract PDF: A large body of evidence indicates that Helicobacter pylori is involved in the pathogenesis of chronic gastritis and peptic ulcers. Several techniques are currently used for detecting H. pylori. Recently the immunohistochemical method was introduced for rapid detection of H. pylori. To compare the result of the immunohistochemical method with those obtained by microbiologic methods, we glean formalin fixed, paraffin embbeded gastric and duodenal biopsy specimens from 85 patients with upper gastrointestinal symptoms. We set fifty cases which H. pylori was cultivated and identified by Gram stain as Group I, and thirty-five cases without H. pylori in Gram stain and culture as Group II. The results were as follows. 1) The sensitivity and the specificity of immunohistochemical method were 94% and 80% compared with the microbiologic method. Positive and negative predictive value of the immunohistochemical method were respectively 87% and 90%. However, in seven cases of Group II, H. pylori were identified by immunohistichemical method. 2) Immunohistochemical staining exhibited bacteria that were present in the mucus layer, the surface of the gastric mucosa and metaplastic gastric epithelium in duodenum. With reference to the distribution and density of H. pylori in Group I and II, a significant correlation existed between microbiologic results and bacterial load of the biopsy specimen (p<0.01). 3) Chronic inflammation of gastric biopsies were seen in all 45 H. pylori-positive cases(100%) and 16 out of 19 H. pylori-negative cases(84%). The degree of chronic inflammation was more severe in positive cases than negative cases. Activity of inflammation was seen 98% of H. pylori-positive cases and 16% of H. pylori-negative cases. Intestinal metaplasia was seen 40% of H. pylori-positive cases and 58% of H. pylori-negative cases. Lymphoid follicles and aggregates were seen in 47%(27 cases) of H. pylori-positive cases. Among 47%, cases with lymphoid follicles were 9%(4 cases) and cases with lymphoid aggregates were 38%(17 cases). In H. pylori-negative cases, lymphoid follicles and aggregates were seen in 16%(3 cases). It is possible to obtain samples from most of the individuals who underwent the endoscopy in Korea. And this method is simple, rapid and sensitive. We conclude that the immunohistochemical method is another useful diagnostic tool for detection of Helicobacter pylori.

Expression of BrdU and C-Ha-ras in Experimentally Induced Enzyme Altered Foci of the Liver and Hepatocellular Carcinoma.: Myung Sook Kim, Woo Ho Kim, Yong Il Kim; Korean J Pathol. 1994;28(6):584-595.

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Abstract PDF: For sequential phenotypic changes including enzyme altered hepatocytic foci, hyperplastic nodules, hepatocellular adenomas and carcinomas were produced in Sprague-Dawley rats by Solt-Farber method (administration of diethylnitrosamine and acetylaminofluorene (AAF), and partial hepatectomy). The immunohistochemical expressions of glutathione S transferase P (GST-P) and bromodeoxyuridine (BrdU) were assessed for selective proliferative activity in the enzyme altered foci and the subsequently developed lesions by double immunohistochemical staining technique. Immunoreactive areas against GSTP gradually increase from early period of carciogenesis. BrdU labeling in such areas remained high during the first week. but decreased thereafter. BrdU labeling index remained low in the GSTP negative area throughout the experimental period. This suggests that cells in the enzyme altered foci keep away from the suppressor effect of AAF in contrast to the normal cells in which their growth are inhibited by AAF. BrdU labeling index remained very low in both hyperplastic nodule and adenoma which were prevalent during the mid-experimental period, but increase markedly in carcinoma. The long period of low BrdU labeling index seems to correspond to the "slowly growing step of persistent nodule" during hepatocarcinogenesis. The differentiation index, a ratio of S phase fraction between GSTP positive and negative areas, was low in adenoma-developing period and high in carcinoma-developing period. C-Ha-ras p21 was not expressed in foci of enzyme altered hepatocyte and hyperplasia, but highly positive in carcinoma. This indicates that the c-Ha-ras may involve the late step of hepatocarcinogenesis.

PLC-gamma1 for Differentiating Adenocarcinoma from Reactive Mesothelial Cells in Effusions.: Woo Yeong Ju, Sung Sook Kim; J Pathol Transl Med. 1997;8(2):115-119.

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Abstract PDF: Cytologic diagnosis of reactive or malignant effusion is sometimes difficult. Espe- cially, differentiation of benign reactive mesothelial cells from malignant cells in body effusion is more difficult. Recently, immunohistochemistry has been used to diagnose difficult cases. Phospholipase C(PLC)-gamma 1 is one of the isoenzyme of the PLC which plays central role in signal transduction involving cellular growth, differentiation and transformation by phosphorylating many protein component. Increased expression of PLC-gamma 1 in human breast carcinoma, colorectal carcinoma and stomach cancers are reported. To evaluate the efficacy of positive PLC-gamma 1 immunostaining in the diagnosis of malignancy in effusions, paraffin-embedded cell blocks of pleural fluid and ascites from 10 patients(5 metastatic adenocarcinomas, and 5 reactive mesothelial cells) were immunostained with a monoclonal antibody to PLC-gamma 1. PLC-gamma 1 immuostained all the adenocarcinomas in cell block(5/5) with intense membrane pattern, however, none of the reactive mesothelial proliferations stained with the diagnostic membrane pattern. Thus, our study strongly supports the conclusion that PLC-gamma 1 immunopositivity is likely to become a useful adjunct for the diagnosis of malignancy in effusions.

Immunohistochemical Study on the Proliferative Activity of Human Thyroid Tumors.: Myoung Jae Kang, Young Jin Jeong, Woo Sung Moon, Myoung Ja Jeong, Joo Heon Kim, Dong Geun Lee, Ho Yeul Choi, Sang Ho Kim; Korean J Pathol. 1995;29(1):77-84.

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Abstract PDF: For the estimation of the proliferative activity, related to the biologic behaviour, malignant potential, and prognosis, of human thyroid tumors, PCNA(proliferating cell nuclear antigen) immunohistochemical staining was performed on paraffin-embedded sections of 9 normal thyroid tissues, 9 adenomatous goiters, 9 follicular adenomas, 4 Hurthle cell tumors, 12 papillary carcinomas, 4 follicular carcinomas, and 3 anaplastic carcinomas. The results were as follows: 1) The PCNA labeling indices in adenomatous goiter, follicular adenoma, and Hurthle cell tumor were 1.1, 1.5, and 2.4, respectively. They were significantly higher than the labeling index in normal thyroid. 2) The PCNA labeling indices in papillary carcinoma and follicular carcinoma were 3.5 and 4.4, respectively. They were significantly higher than the labeling indices in adenomatous goiter and follicular adenoma, but there was no significant difference between papillary and follicular carcinoma. 3) The PCNA labeling index in anaplastic carcinoma, 14.1, was significantly higher than those in benign and other malignant tumors. According to the results, the PCNA labeling index was well correlated with the malignant potential of a tumor. So the PCNA immunohistochemical staining is thought to be a useful method for the evaluation of the malignant potential and prognosis of a tumor.

Immunohistochemical Study of Cytokeratin in Human Trophoblastic Tissue.: Jeong Hee Kang, Kang Suek Suh; Korean J Pathol. 1992;26(5):459-465.

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Abstract PDF: The use of human chorionic gonadotropin(hCG), human placental lactogen(hPL) as markers for trophoblastic tissue has been well documented in the literature. However, it is not widely recognized that cytokeratin is a very sensitive and reliable marker for various types of trophoblastic tissue. The authors have studied 15 cases of human placental tissue ranging in age from first to third trimesters. Unlike hCG and hPL, which stain only the syncytiotrophoblast and intermediate trophoblast, cytokeratin(low molecular weight) stains all three types trophoblastic tissue. The staining of placental tissue for cytokeratin is marked and very consistent throughout pregnancy. Because of its high sensitivity and ability to stain cytotrophoblast, it is believed that it could be very useful in detecting trophoblasts of early pregnancy and in the study of the pathologic process of trophoblastic diseases.

Effect of Lysodren(R) on the Ultrastructural Changes in the Rat Adrenal Corex: Immunohistochemical staining for anti-ACTH antibody on the adenohypophysis.: Ho Jong Chun, Hae Chang Cho, Hae Sook Song, Kyu Ho Park; Korean J Pathol. 1989;23(1):94-110.

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Abstract PDF: The toxicity and adrenostatic effect of o,p'-DDD, a derivative of the insecticidal DDT, on the adrenal cortex were well known. It known that the toxicity was based on the blocking of steroid biopsynthesis when cholesterol was converted to pregnenolone. Lysodren(R) was also known to be capable of producing a regression of adrenocortical carcinoma and its metastases, and this drug became one of useful choice for the treatment of unoperable adrenocortical carcinomas. Recently, fine structural effect of o,p'-DDD on the adrenocortical carcinoma show that the mitochondria is the primary target organelle. o,p'-DDD was dissolved in corn oil and it was orally administered for 28 days to investigate the ultrastructural effects of zona fasciculata of rat adrenal cortex. The results obtained were as follow: 1) The body weight was decreased after feeding o,p'-DDD. 2) Light microscopic examination showed no remarkable change except increased fine lipid droplets of zona fasciculata in group I (o,p'-DDD 75 mg/kg feeding). Moderately increased intracytoplasmic lipid droplets and pyknotic nuclei bearing membrane indentations were seen in group II (o,p'-DDD 150 mg/kg feeding). Large sized lipid droplet aggregates, pyknotic nuclei with severe nuclear membrane indentations and karyorrhexis in focal area were evident in group III. 3) Immunohistochemical staining for ACTH in pituitary gland showed increasing number of ACTH secretory cell and increasing intensity of staining property according to the dosage of o,p'-DDD. 4) Ultrastructural examination showed increased intracytoplasmic lipid droplets and mild increased peroxisome. There was no remarkable ultrastructural changes in mitochondria in group I. Moderately increased lipid droplets and clusters formation, compressed mitochondria, partial disappearance of mitochondrial cristae, increased peroxisome and nuclear membrane indentations were seen in group II. In group III, nuclear membrane showed prominent indentation. Numberous cytoplasmic vacuolation, double membrane ring in mitochondria, disappearance of mitochondrial cristae, myelin figure formation in mitochondrial matrix, and fatty changes in mitochondrial matrix were seen. These findings showed that the primary target organelle of attack by o,p'-DDD on zona fasciculata of adrenal gland in rat is mitochondria and it was developed from double ring formation in mitochondrial matrix.

A Study on Immunohistochemical Stain for S-100 Protein, HMB 45 and Proliferating Cell Nuclear Antigen(PCNA) of Spitz Nevus Compared with Benign Nevus and Malignant Melanoma.: Mee Yon Cho, Kwang Gil Lee, Myung Wook Kim; Korean J Pathol. 1992;26(6):552-560.

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Abstract PDF: The differential diagnosis between Spitz nevus and malignant melanoma is difficult due to similar histologic findings. To obtain the useful aids for the differential diagnosis between two diseases, we studied 13 cases of Spitz nevus, 8 benign nevi of compound and intradermal, and 9 melanomas of primary and metastatic, using the immunohistochemical stain for S-100 protein, HMB.45 and proliferating cell nuclear antigen(PCNA). The staining pattern and intensity of S-100 protein showed homogenously strong positive reactivity in all cases. The frequency of HMB.45 positive cell in Spitz nevus was significantly lower than that in melanoma. When compared with the usual compound and intradermal nevi, Spitz nevi showed more significantly positive reaction in the dermal component of nevus cells. The expression of PCNA was higher in melanoma than in Spitz nevus. The immunohistochemical stains for HMB.45 and PCNA are considered as a useful methods for differentiation between Spitz nevus and melanoma, while stain for S-100 protein is not helpful.

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