Journal of Pathology and Translational Medicine

Original Articles

Multistaining Optimization for Epstein-Barr Virus–Encoded RNA In Situ Hybridization and Immunohistochemistry of Formalin-Fixed Paraffin-Embedded Tissues Using an Automated Immunostainer: Jae Nam Ko, Jin Kyoung Jung, Yun Ik Park, Hwa Jeong Shin, Jooryung Huh, Sol Back, Yu Jin Kim, Jae Ho Kim, Heounjeong Go; J Pathol Transl Med. 2019;53(5):317-326. Published online August 27, 2019; DOI: https://doi.org/10.4132/jptm.2019.08.06

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Background
Single staining is commonly performed for practical pathologic diagnoses. However, this method is limited in its ability to specify cellular morphology and immunophenotype and often requires consumption of limited tissue. This study aimed to describe an optimized protocol for multiple in situ hybridization (ISH) and immunohistochemistry (IHC).
Methods
The quality of multistaining was evaluated by carefully changing each step of ISH and IHC in an angioimmunoblastic T-cell lymphoma (AITL) case on a Ventana BenchMark XT automated immunostainer. The optimized protocols were also performed using another immunostainer and in 15 cases of five Epstein-Barr virus (EBV)–associated malignancies using formalin-fixed paraffin-embedded tissue.
Results
The quality of various ISHIHC staining protocols was semi-quantitatively evaluated. The best EBV-encoded RNA (EBER)-ISH/double IHC staining quality, equivalent to single staining, was obtained using the following considerations: initial EBER-ISH application, use of protease and antigen retrieval reagent (cell conditioning 1 [CC1] treatment time was minimized due to impact on tissue quality), additional baking/ deparaffinization not needed, and reduced dilution ratio and increased reaction time for primary antibody compared with single immunostaining. Furthermore, shorter second CC1 treatment time yielded better results. Multiple staining was the best quality in another immunostainer and for different types of EBV-associated malignancies when it was performed in the same manner as for the Ventana BenchMark XT as determined for AITL.
Conclusions
EBER-ISH and double IHC could be easily used in clinical practice with currently available automated immunostainers and adjustment of reagent treatment time, dilution ratio, and antibody reaction time.

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Ultra High-plex Spatial Proteogenomic Investigation of Giant Cell Glioblastoma Multiforme Immune Infiltrates Reveals Distinct Protein and RNA Expression Profiles
Shilah A. Bonnett, Alyssa B. Rosenbloom, Giang T. Ong, Mark Conner, Aric B.E. Rininger, Daniel Newhouse, Felicia New, Chi Q. Phan, Saskia Ilcisin, Hiromi Sato, John S. Lyssand, Gary Geiss, Joseph M. Beechem
Cancer Research Communications.2023; 3(5): 763. CrossRef
Detection of Epstein–Barr Virus in Periodontitis: A Review of Methodological Approaches
Lilit Tonoyan, Marlène Chevalier, Séverine Vincent-Bugnas, Robert Marsault, Alain Doglio
Microorganisms.2020; 9(1): 72. CrossRef

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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Abstract PDF

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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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
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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

Loss of Nuclear BAP1 Expression Is Associated with High WHO/ISUP Grade in Clear Cell Renal Cell Carcinoma: Young Chan Wi, Ahrim Moon, Min Jung Jung, Yeseul Kim, Seong Sik Bang, Kiseok Jang, Seung Sam Paik, Su-Jin Shin; J Pathol Transl Med. 2018;52(6):378-385. Published online October 1, 2018; DOI: https://doi.org/10.4132/jptm.2018.09.21

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196 Download
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Abstract PDF

Background
BRCA1-associated protein 1 (BAP1) mutations are frequently reported in clear cell renal cell carcinoma (ccRCC); however, very few studies have evaluated the role of these mutations in other renal cell carcinoma (RCC) subtypes. Therefore, we analyzed BAP1 protein expression using immunohistochemistry in several RCC subtypes and assessed its relationship with clinicopathological characteristics of patients.
Methods
BAP1 expression was immunohistochemically evaluated in tissue microarray blocks constructed from 371 samples of RCC collected from two medical institutions. BAP1 expression was evaluated based on the extent of nuclear staining in tumor cells, and no expression or expression in < 10% of tumor cells was defined as negative.
Results
Loss of BAP1 expression was observed in ccRCC (56/300, 18.7%), chromophobe RCC (6/26, 23.1%), and clear cell papillary RCC (1/4, 25%), while we failed to detect BAP1 expression loss in papillary RCC, acquired cystic disease-associated RCC, or collecting duct carcinoma. In ccRCC, loss of BAP1 expression was significantly associated with high World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grade (p = .002); however, no significant correlation was observed between loss of BAP1 expression and survival in ccRCC. Loss of BAP1 expression showed no association with prognostic factors in chromophobe RCC.
Conclusions
Loss of BAP1 nuclear expression was observed in both ccRCC and chromophobe RCC. In addition, BAP1 expression loss was associated with poor prognostic factors such as high WHO/ISUP grade in ccRCC.

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Review

Immunohistochemistry for Pathologists: Protocols, Pitfalls, and Tips: So-Woon Kim, Jin Roh, Chan-Sik Park; J Pathol Transl Med. 2016;50(6):411-418. Published online October 13, 2016; DOI: https://doi.org/10.4132/jptm.2016.08.08

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1,648 Download
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Abstract PDF

Immunohistochemistry (IHC) is an important auxiliary method for pathologists in routine diagnostic work as well as in basic and clinical research including exploration of biomarkers, as IHC allows confirmation of target molecule expressions in the context of microenvironment. Although there has been a considerable progress in automation and standardization of IHC, there are still many things to be considered in proper optimization and appropriate interpretation. In this review, we aim to provide possible pitfalls and useful tips for practicing pathologists and residents in pathology training. First, general procedure of IHC is summarized, followed by pitfalls and tips in each step and a summary of troubleshooting. Second, ways to an accurate interpretation of IHC are discussed, with introduction to general quantification and analysis methods. This review is not intended to provide complete information on IHC, but to be used as a basic reference for practice and publication.

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Original Articles

Expression of CD99 in Multiple Myeloma: A Clinicopathologic and Immunohistochemical Study of 170 Cases: Su-Jin Shin, Hyangsin Lee, Geunyoung Jung, Minchan Gil, Hosub Park, Young Soo Park, Dok Hyun Yoon, Cheolwon Suh, Chan-Jeoung Park, Jooryung Huh, Chan-Sik Park; Korean J Pathol. 2014;48(3):209-216. Published online June 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.3.209

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Abstract PDF

Background

Multiple myeloma (MM) is a heterogeneous and ultimately fatal disease. Risk stratification using prognostic biomarkers is crucial to individualize treatments. We sought to investigate the role of CD99, a transmembrane protein highly expressed in many hematopoietic cells including subpopulations of normal and neoplastic plasma cells, for MM risk stratification.

Methods

CD99 expression was measured in paraffin samples of bone marrow and extramedullary biopsies of 170 patients with MM. Patients were divided into those with high score (moderately and strongly positive) and low score (negative and weakly positive), with all staining being cytoplasmic and/or membranous.

Results

High anti-CD99 immunostaining was observed in 72 of 136 (52.9%) bone marrow biopsies and 24 of 87 (27.6%) extramedullary biopsies in MM. High CD99 expression of extramedullary specimens was associated with significantly longer overall survival (OS; p=.016). High CD99 expression of extramedullary specimens was also associated with better prognosis in the nonautologous stem cell transplantation group of MM patients (p=.044). In multivariate analysis, International Staging System stage was an independent prognostic factor, whereas CD99 expression was no longer statistically significant.

Conclusions

Expression of CD99 in extramedullary specimens was correlated with longer OS, suggesting that CD99 may be a helpful immunohistochemical marker for risk stratification.

Citations

Citations to this article as recorded by

Cell Adhesion Molecule CD99 in Cancer Immunotherapy
Feng Yu, Guodong Liu, Hailing Zhang, Xiaoyan Wang, Zhi Wu, Qinggang Xu, Yan Wu, Dongfeng Chen
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Detection of Circulating Tumor Plasma Cells in Monoclonal Gammopathies: Methods, Pathogenic Role, and Clinical Implications
Luzalba Sanoja-Flores, Juan Flores-Montero, Martín Pérez-Andrés, Noemí Puig, Alberto Orfao
Cancers.2020; 12(6): 1499. CrossRef
Tumor suppressor CD99 is downregulated in plasma cell neoplasms lacking CCND1 translocation and distinguishes neoplastic from normal plasma cells and B-cell lymphomas with plasmacytic differentiation from primary plasma cell neoplasms
Qi Gao, Venkata Yellapantula, Maly Fenelus, Janine Pichardo, Lu Wang, Ola Landgren, Ahmet Dogan, Mikhail Roshal
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Human Myeloma Cell Lines Induce Osteoblast Downregulation of CD99 Which Is Involved in Osteoblast Formation and Activity
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Evaluation of Bronchiolar and Alveolar Cell Injuries Induced by Short- and Long-term Exposure to Sidestream Smoke: Kun-Young Kwon, Hye-Ra Jung, Ilseon Hwang, Won-Il Choi; Korean J Pathol. 2012;46(2):151-161. Published online April 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.2.151

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Abstract PDF

Background

We investigated effects of short- and long-term exposure to sidestream smoke on the bronchiolar and alveolar cells in Sprague-Dawley rats.

Methods

Rats were divided into five experimental groups: groups 1, 2, and 3 (1-month exposure to 3, 5, and 7 cigarettes a day, respectively), groups 4 and 5 (3- and 6 month exposure to five cigarettes a day, respectively). We examined the morphologic changes, the expressions of tumor necrosis factor α (TNF-α), tumor growth factor β1 (TGF-β1), interlekin (IL)-1α, IL-1β, Ki-67, and cytokeratin 14 and in situ apoptosis in the bronchiolar and alveolar cells on light microscopy (LM) and electron microscopic (EM) terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining.

Results

LM showed the respiratory bronchiolar dilatation and alveolar wall collapse. In groups 3, 4, and 5, EM showed loss of the cilia and Clara cells with irregular size, more prominent alveolar wall collapse and dilation of alveolar duct than those of groups 1 and 2. Bronchiolar and alveolar cells showed increased expressions of TNF-α and TGF-β in groups 4 and 5. LM and EM TUNEL stains showed increased apoptosis in groups 3, 4, and 5.

Conclusions

Sidestream smoke causes a bronchiolar and alveolar cell injury and the severity correlates strongly the volume and duration of exposure to sidestream smoke.

Citations

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Cigarette smoke extract alters the cell cycle via the phospholipid transfer protein/transforming growth factor-β1/CyclinD1/CDK4 pathway
Xue-Min Chai, You-Lun Li, Hong Chen, Shu-Liang Guo, Li-Li Shui, Ya-Juan Chen
European Journal of Pharmacology.2016; 786: 85. CrossRef
Keratin-14 Expression in Pneumocytes as a Marker of Lung Regeneration/Repair during Diffuse Alveolar Damage
Miriam Ficial, Caterina Antonaglia, Marco Chilosi, Mario Santagiuliana, Al-Omoush Tahseen, Davide Confalonieri, Lorenzo Zandonà, Rossana Bussani, Marco Confalonieri
American Journal of Respiratory and Critical Care Medicine.2014; 189(9): 1142. CrossRef

Case Report

Cytologic Findings of Alveolar Soft Part Sarcoma Presenting with Multiple Pulmonary Masses: A Case Report with Review of Literature.: Na Rae Kim, Jae Y Ro, Eun Kyung Cho, Mi Jin Kim, Jungsuk An, Seung Yeon Ha; Korean J Pathol. 2011;45(1):119-124.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.119

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Abstract PDF

Alveolar soft part sarcoma (ASPS) is a rare malignant soft tissue tumor of uncertain origin, and it has a strong propensity for metastasis to the lungs, bones and brain. We report upon an unusual case of ASPS, presenting as multiple lung nodules with no other detectable primary site, in a 44-year-old man. A fine needle aspiration of the nodules yielded scattered, discohesive cells, each containing an eccentrically displaced nucleus and prominent nucleolus, on a granular background. Tumor cells with numerous bared nuclei, and occasional sheets of epithelioid cells were also found. Under the cytological diagnosis of an unclassified epithelioid malignant tumor, resection of the lung nodules was performed. The histologic findings were consistent with ASPS, showing positive TFE3-nuclear immunoreactivity. There is limited literature concerning cytological findings associated with pulmonary ASPS: especially in cases where the primary site is unknown. Here, we present a cytological review of pulmonary ASPS, investigating the significance of TFE3 staining in the diagnosis of ASPS.

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Alveolar soft part sarcoma: A case report with emphasis on some unusual cytological features
Neelam Sood, Minakshi Gulia
Diagnostic Cytopathology.2018; 46(2): 170. CrossRef

Original Articles

Comparison of Various Detection Methods of Mycobacterium Species in Formalin-Fixed Paraffin-Embedded Tissue with Chronic Granulomatous Inflammation.: Hyun Seung Lee, Hyoungnam Lee, Soyoung Im, Yun Su Lee, Kyo Young Lee, Yeong Jin Choi; Korean J Pathol. 2010;44(3):259-266.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.259

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Abstract PDF

BACKGROUND
To determine the most effective method for detecting mycobacteria in formalin- fixed paraffin-embedded (FFPE) tissue, we compared the results of Ziehl-Neelsen stain (ZNS) and mycobacterial culture with those of polymerase chain reaction (PCR) and real-time quantitative PCR (RQ-PCR).
METHODS
We analyzed 54 cases diagnosed as chronic granulomatous inflammation. In all cases, ZNS and nested PCR using three different primers, IS6110, Mpb64 and IS6110/Rpobeta were done. RQ-PCR with the IS6110/Rpobeta primer was done in 51 cases.
RESULTS
Mycobacteria were identified by ZNS in 15/54 (27.8%) cases. RQ-PCR had the highest sensitivity (80.0%) compared to PCR with IS6110 (73.3%), Mpb64 (60.0%) and IS6110/Rpobeta (73.3%). Specificity was higher in all PCR experiments (79.5-82.1%) than in RQ-PCR (69.4%) experiments. The false negative rate was lowest for RQ-PCR (20.0%) than for PCR with IS6110 (26.7%), Mpb64 (40.0%) and IS6110/Rpobeta (26.7%). The false positive rate was highest for RQ-PCR (30.6%) compared to PCR with IS6110 (20.5%), Mpb64 (17.9%) and IS6110/Rpobeta (20.5%).
CONCLUSIONS
RQ-PCR had the highest sensitivity, and the lowest false negative rate, but it also had a higher false positive rate than PCR for detection of mycobacteria in FFPE tissues.

Citations

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Clinical Usefulness of PCR for Differential Diagnosis of Tuberculosis and Nontuberculous Mycobacterial Infection in Paraffin-Embedded Lung Tissues
Yo Na Kim, Kyoung Min Kim, Ha Na Choi, Ju Hyung Lee, Ho Sung Park, Kyu Yun Jang, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee, Myoung Ja Chung
The Journal of Molecular Diagnostics.2015; 17(5): 597. CrossRef
Usefulness of PCR to Mycobacterium Tuberculous and Nontuberculous Mycobacteria from Paraffin-embedded Tissues
Yeon-Il Choi, Hye-Young Kim
Korean Journal of Clinical Laboratory Science.2014; 46(2): 47. CrossRef

The Cytology for Leukemic Cells in Cerebrospinal Fluid; Comparison of Conventional Cytology with Liquid-Based Cytology.: Changyoung Yoo, Youn Soo Lee, Chang Suk Kang, Sang In Shim, Kyo Young Lee; Korean J Pathol. 2009;43(2):164-170.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.2.164

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Abstract PDF: BACKGROUND
The cytological examination of cerebrospinal fluid (CSF) using conventional cytology with a cytocentrifuge (cytospin) is an important method for evaluating the involvement of leukemia in the CNS. Liquid-based cytology (LBC) is now a widely used cytological method not only for gynecological and non-gynecological specimens, but its application to CSF for the identification of leukemic cell has not yet been reported. In this study, we tried to compare conventional cytology with using a cytospin with LBC and Papanicolaou (Pap) staining. We also examined the modified LBC with Wright staining to assess whether this modified method can be useful for diagnosing Leukemia.
METHODS
We studied 30 cases of CSF that were obtained from 16 patients, including 17 cases of acute myeloid leukemia, 12 cases of acute lymphoblastic leukemia and 1 case of diffuse large B cell lymphoma. We applied conventional cytology with a cytocentrifuge (cytospin), LBC with Pap staining and modified LBC with Wright staining.
RESULTS
The morphological features of the LBC with Pap staining showed difficulty for interpretation when compared with conventional cytology with a cytospin, and mainly because of cellular shrinkage. The modified LBC with Wright staining showed good morphological features.
CONCLUSIONS
We suggest that modified LBC with Wright staining may be useful for examining CSF.

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.

Expression of p53 Protein and c-erbB-2 Oncoprotein in Breast Carcinoma.: Eun Hee Lee, Dong Sug Kim, Tae Sook Lee, Soo Jung Lee; Korean J Pathol. 1995;29(5):596-606.

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Abstract: This study was conducted to evaluate the expression of p53 and c-erbB-2 using immuno-histochemical methods in 145 primary breast carcinomas and to correlate it with other histo-pathological prognostic factors. Invasive ductal carcinoma represented 129 of the cases. Expression of p53 protein and c-erbB-2 oncoprotein was present in 48% (62/129) and 30% (39/129) of invasive ductal carcinomas, respectively. The expression of p53 protein was stongly associated with a high score of degree of differentiation (p<0.05), nuclear pleomorphism (p<0.05), mitotic index (p<0.05), SBR grade (p<0.05) and MSBR grade (p<0.05), but it was not associated with patient's age, size of tumor or axillary node metastasis. The overexpression of c-erbB-2 C-erbB-2 oncoprotein was strongly associated with a high score of nuclear pleomorphism and a high SBR grade (p<0.05), but not associated with patient's age, size of tumor, axillary node metastasis, degree of differentiation, mitotic index or MSBR grade. An inverse relationship between the expression of p53 protein and estrogen receptor status was found, but the expression of c-erbB-2 was not associated with estrogen receptor status. It is concluded that p53 protein and c-erbB-2 oncoprotein are important prognostic factors in breast cancers, and that the aberrant expression of p53 protein is the most useful prognostic factor becausd of strong association of known histopathological prognostic factors and negative estrogen receptor status.

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.

Immunohistochemical Analysis of HLA-DR and Secretory Component Expression in Gastric Adenocarcinoma.: Ji Youn Bae, Soo Sang Sohn, Eun Sook Chang; Korean J Pathol. 1996;30(4):293-300.

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Abstract PDF: Sixty one cases of gastric adenocarcinoma were studied immunohistochemically for expression of HLA-DR and secretory component(SC) in order to analyze the relationship between expression of these in gastric cancer cells and the adjacent mucosa. Immunostaining was detected within the cytoplasm and on the cell memgrane. The rate of HLA-DR and SC expressions in cancer cells were 59.0% and 49.2%, respectively, and 52.5%/52.5% and 31.2%/50.8% the mucosa in adjacent/remote from the site of to cancer. The SC expression in the adjacent mucosa was lower than that of the remote mucosa(p=0.027). The HLA-DR expression in the cancer cells in the intestinal type of gastric adenocarcinoma(73.9%) was higher than that of the diffuse type(14.3%) and it was statistically significant(p=0.02). The presence of an increased amount of lymphoid infiltration in the gastric mucosa was closely related to the expression of HLA-DR and SC. Decreased or absent expression of SC at the transitional mucosal cells was possibly a result of exposure to genotoxic agents due to the lack of protective function of SC-IgA. From these results, one can postulate that the expression of HLA-DR and SC may play an important role in atleration in microenvironment with lymphoid infiltration.

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.

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