Journal of Pathology and Translational Medicine

Original Articles

TERT mutations and aggressive histopathologic characteristics of radioiodine-refractory papillary thyroid cancer: Ju Yeon Pyo, Yoon Jin Cha, SoonWon Hong; J Pathol Transl Med. 2024;58(6):310-320. Published online September 12, 2024; DOI: https://doi.org/10.4132/jptm.2024.07.29

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Abstract PDF: Background
Radioiodine (RI) ablation following thyroid-stimulating hormone suppression is an effective treatment for papillary thyroid cancer (PTC), typically leading to favorable outcomes. However, RI-refractory tumors exhibit aggressive behavior and poor prognoses. Recent studies highlight the role of genetic abnormalities in PTC signaling pathways, including the activation of telomerase reverse transcriptase (TERT), and the correlation of mutations with adverse outcomes.
Methods
This study analyzed mutations in BRAF V600E and the TERT-promoter genes, comparing clinicopathological features between RI-refractory and RI-responsive PTCs. Among 82 RI-refractory patients, formalin-fixed, paraffin-embedded tissues from initial surgeries were available for 26. Another 89 without distant metastasis over 5 years formed a matched RI-responsive control group.
Results
Histopathologically, RI-refractory PTCs showed increased frequencies of small tumor clusters without fibrovascular cores, hobnail features, and a high height-to-width ratio of tumor cells. These tumors were more likely to exhibit necrosis, mitosis, lymph node metastasis, extrathyroidal extension, and involvement of resection margins. TERT-promoter mutations were statistically significantly associated with these aggressive clinicopathologic features. Immunohistochemically, decreased expression of sodium iodide symporter and thyroglobulin stimulating hormone receptor proteins was common in RI-refractory PTCs, along with lower levels of oncogenic proteins such as vascular endothelial cell growth factor, vascular endothelial cell growth factor receptor 2, and nuclear factor kappa-light-chain-enhancer of activated B cells. Total loss of PTEN expression was occasionally observed. In contrast, all cases tested positive for cytoplasmic β-catenin.
Conclusions
RI-refractory PTCs are linked to TERT mutations and exhibit specific aggressive histopathologic features, particularly in tumor centers.

A Multi-institutional Study of Prevalence and Clinicopathologic Features of Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) in Korea: Ja Yeong Seo, Ji Hyun Park, Ju Yeon Pyo, Yoon Jin Cha, Chan Kwon Jung, Dong Eun Song, Jeong Ja Kwak, So Yeon Park, Hee Young Na, Jang-Hee Kim, Jae Yeon Seok, Hee Sung Kim, Soon Won Hong; J Pathol Transl Med. 2019;53(6):378-385. Published online October 21, 2019; DOI: https://doi.org/10.4132/jptm.2019.09.18

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Background
In the present multi-institutional study, the prevalence and clinicopathologic characteristics of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) were evaluated among Korean patients who underwent thyroidectomy for papillary thyroid carcinoma (PTC).
Methods
Data from 18,819 patients with PTC from eight university hospitals between January 2012 and February 2018 were retrospectively evaluated. Pathology reports of all PTCs and slides of potential NIFTP cases were reviewed. The strict criterion of no papillae was applied for the diagnosis of NIFTP. Due to assumptions regarding misclassification of NIFTP as non-PTC tumors, the lower boundary of NIFTP prevalence among PTCs was estimated. Mutational analysis for BRAF and three RAS isoforms was performed in 27 randomly selected NIFTP cases.
Results
The prevalence of NIFTP was 1.3% (238/18,819) of all PTCs when the same histologic criteria were applied for NIFTP regardless of the tumor size but decreased to 0.8% (152/18,819) when tumors ≥1 cm in size were included. The mean follow-up was 37.7 months and no patient with NIFTP had evidence of lymph node metastasis, distant metastasis, or disease recurrence during the follow-up period. A difference in prevalence of NIFTP before and after NIFTP introduction was not observed. BRAF^V600E mutation was not found in NIFTP. The mutation rate for the three RAS genes was 55.6% (15/27).
Conclusions
The low prevalence and indolent clinical outcome of NIFTP in Korea was confirmed using the largest number of cases to date. The introduction of NIFTP may have a small overall impact in Korean practice.

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Case report & review: Bilateral NIFTP harboring concomitant HRAS and KRAS mutation: Report of an unusual case and literature review
Marianna Rita Brogna, Francesca Collina, Maria Grazia Chiofalo, Debora De Bartolo, Angela Montone, Maria Rosaria Schiano, Michele Del Sesto, Nubia Pizza, Gerardo Ferrara
Molecular Carcinogenesis.2024; 63(12): 2273. CrossRef
Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): what do we need to know?
Andrés Coca-Pelaz, Juan P. Rodrigo, Abbas Agaimy, Dana M. Hartl, Göran Stenman, Vincent Vander Poorten, Antti A. Mäkitie, Mark Zafereo, Karthik N. Rao, Gregory W. Randolph, Alessandra Rinaldo, Alfio Ferlito
Virchows Archiv.2024; 485(6): 977. CrossRef
Study of non-invasive follicular thyroid neoplasm: A borderline entity
Rupali Bavikar, Ruchi S. Randive, Anubhaw Verma, Madhuri Singh, Vidya Viswanathan, Arpana Dharwadkar
Journal of Cancer Research and Therapeutics.2024; 20(5): 1365. CrossRef
Analysis of a pre-2017 follicular variant papillary thyroid carcinoma cohort reclassified as noninvasive follicular thyroid neoplasm with papillary-like features (NIFTP): an 11-year retrospective single institution experience
Shaham Beg, Sana Irfan Khan, Isabella Cui, Theresa Scognamiglio, Rema Rao
Journal of the American Society of Cytopathology.2023; 12(2): 112. CrossRef
Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features: What a Surgeon Should Know
Jabir Alharbi, Thamer Alraddadi, Haneen Sebeih, Mohammad A Alessa, Haddad H Alkaf, Ahmed Bahaj, Sherif K Abdelmonim
Cureus.2023;[Epub] CrossRef
NTRK Fusion in a Cohort of BRAF p. V600E Wild-Type Papillary Thyroid Carcinomas
Seung Eun Lee, Mi-Sook Lee, Heejin Bang, Mi Young Kim, Yoon-La Choi, Young Lyun Oh
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A Comprehensive Study on the Diagnosis and Management of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features
Bayan A. Alzumaili, Lauren N. Krumeich, Reagan Collins, Timothy Kravchenko, Emad I. Ababneh, Adam S. Fisch, William C. Faquin, Vania Nosé, Maria Martinez-Lage, Gregory W. Randolph, Rajshri M. Gartland, Carrie C. Lubitz, Peter M. Sadow
Thyroid.2023; 33(5): 566. CrossRef
Clinical-Pathological and Molecular Evaluation of 451 NIFTP Patients from a Single Referral Center
Paola Vignali, Agnese Proietti, Elisabetta Macerola, Anello Marcello Poma, Liborio Torregrossa, Clara Ugolini, Alessio Basolo, Antonio Matrone, Teresa Rago, Ferruccio Santini, Rossella Elisei, Gabriele Materazzi, Fulvio Basolo
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Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: its updated diagnostic criteria, preoperative cytologic diagnoses and impact on the risk of malignancy
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Journal of Pathology and Translational Medicine.2022; 56(6): 319. CrossRef
SFE-AFCE-SFMN 2022 Consensus on the management of thyroid nodules : Follow-up: How and how long?
Sophie Leboulleux, Livia Lamartina, Emmanuelle Lecornet Sokol, Fabrice Menegaux, Laurence Leenhardt, Gilles Russ
Annales d'Endocrinologie.2022; 83(6): 407. CrossRef
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Clinicopathological parameters for predicting non-invasive follicular thyroid neoplasm with papillary features (NIFTP)
Eunju Jang, Kwangsoon Kim, Chan Kwon Jung, Ja Seong Bae, Jeong Soo Kim
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Thyroid.2021;[Epub] CrossRef
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Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is rare, benign lesion using modified stringent diagnostic criteria: Reclassification and outcome study
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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.

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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
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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

Preoperative Cytologic Diagnosis of Warthin-like Variant of Papillary Thyroid Carcinoma: Jisup Kim, Beom Jin Lim, Soon Won Hong, Ju Yeon Pyo; J Pathol Transl Med. 2018;52(2):105-109. Published online February 12, 2018; DOI: https://doi.org/10.4132/jptm.2017.12.26

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Abstract PDF

Background
Warthin-like variant of papillary thyroid carcinoma (WLV-PTC) is a relatively rare variant of papillary thyroid carcinoma with favorable prognosis. However, preoperative diagnosis using fine-needle aspiration (FNA) specimens is challenging especially with lymphocytic thyroiditis characterized by Hürthle cells and lymphocytic background. To determine a helpful cytological differential point, we compared WLV-PTC FNA findings with conventional papillary thyroid carcinoma with lymphocytic thyroiditis (PTC-LT) and conventional papillary thyroid carcinoma without lymphocytic thyroiditis (PTC) regarding infiltrating inflammatory cells and their distribution. Preoperative diagnosis or potential for WLV-PTC will be helpful for surgeons to decide the scope of operation.
Methods
Of the 8,179 patients treated for papillary thyroid carcinoma between January 2007 and December 2012, 16 patients (0.2%) were pathologically confirmed as WLV-PTC and four cases were available for cytologic review. For comparison, we randomly selected six PTC-LT cases and five PTC cases during the same period. The number of intratumoral and background lymphocytes, histiocytes, neutrophils, and the presence of giant cells were evaluated and compared using conventional smear and ThinPrep preparations.
Results
WLV-PTC showed extensive lymphocytic smear with incorporation of thyroid follicular tumor cell clusters and frequent histiocytes. WLV-PTC was associated with higher intratumoral and background lymphocytes and histiocytes compared with PTC-LT or PTC. The difference was more distinct in liquid-based cytology.
Conclusions
The lymphocytic smear pattern and the number of inflammatory cells of WLV-PTC are different from those of PTC-LT or PTC and will be helpful for the differential diagnosis of WLV-PTC in preoperative FNA.

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An Algorithmic Approach to Defining Variants of Papillary Thyroid Carcinoma: Accuracy of Fine Needle Aspiration Cytology
Neha Nigam, Neha Kumari, Rishabh Sahai, Nandita Chaudhary, Sabaretnam Mayilvaganan, Pallavi Prasad, Prabhakar Mishra
Journal of Cytology.2025; 42(1): 27. CrossRef
Warthin-like variant of papillary thyroid carcinoma with lymph node metastases: a case report and review of the literature
Andrii Hryshchyshyn, Andrii Bahrii, Pavlina Botsun, Volodymyr Chuba
Journal of Medical Case Reports.2024;[Epub] CrossRef
Cytologic hallmarks and differential diagnosis of papillary thyroid carcinoma subtypes
Agnes Stephanie Harahap, Chan Kwon Jung
Journal of Pathology and Translational Medicine.2024; 58(6): 265. CrossRef
Warthin-like papillary thyroid carcinoma: a case report and comprehensive review of the literature
Abdel Mouhaymen Missaoui, Fatma Hamza, Wafa Belabed, Manel Mellouli, Mohamed Maaloul, Slim Charfi, Issam Jardak, Tahya Sellami-Boudawara, Nabila Rekik, Mohamed Abid
Frontiers in Endocrinology.2023;[Epub] CrossRef
The Warthin-like variant of papillary thyroid carcinomas: a clinicopathologic analysis report of two cases
Xing Zhao, Yijia Zhang, Pengyu Hao, Mingzhen Zhao, Xingbin Shen
Oncologie.2023; 25(5): 581. CrossRef
Challenges in Cytology Specimens With Hürthle Cells
Eleni Thodou, Sule Canberk, Fernando Schmitt
Frontiers in Endocrinology.2021;[Epub] CrossRef
Warthin-like variant of Papillary thyroid carcinoma—Case report of an uncommon tumour with review of literature
Pradyumna Kumar Sahoo, Rashmi Patnayak, Perwez Alam Khan, Amitabh Jena
International Journal of Surgery Case Reports.2020; 77: 9. CrossRef

Review

Thyroid Fine-Needle Aspiration Cytology Practice in Korea: Yoon Jin Cha, Ju Yeon Pyo, SoonWon Hong, Jae Yeon Seok, Kyung-Ju Kim, Jee-Young Han, Jeong Mo Bae, Hyeong Ju Kwon, Yeejeong Kim, Kyueng-Whan Min, Soonae Oak, Sunhee Chang; J Pathol Transl Med. 2017;51(6):521-527. Published online October 11, 2017; DOI: https://doi.org/10.4132/jptm.2017.09.26

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Abstract PDF

We reviewed the current status of thyroid fine-needle aspiration cytology (FNAC) in Korea. Thyroid aspiration biopsy was first introduced in Korea in 1977. Currently, radiologists aspirate the thyroid nodule under the guidance of ultrasonography, and cytologic interpretation is only legally approved when a cytopathologist makes the diagnosis. In 2008, eight thyroid-related societies came together to form the Korean Thyroid Association. The Korean Society for Cytopathology and the endocrine pathology study group of the Korean Society for Pathologists have been updating the cytologic diagnostic guidelines. The Bethesda System for Reporting Thyroid Cytopathology was first introduced in 2009, and has been used by up to 94% of institutions by 2016. The average diagnosis rates are as follows for each category: I (12.4%), II (57.9%), III (10.4%), IV (2.9%), V (3.7%), and VI (12.7%). The malignancy rates in surgical cases are as follows for each category: I (28.7%), II (27.8%), III (50.6%), IV (52.3%), V (90.7%), and VI (100.0%). Liquid-based cytology has been used since 2010, and it was utilized by 68% of institutions in 2016. The categorization of thyroid lesions into “atypia of undetermined significance” or “follicular lesion of undetermined significance” is necessary to draw consensus in our society. Immunocytochemistry for galectin-3 and BRAF is used. Additionally, a molecular test for BRAF in thyroid FNACs is actively used. Core biopsies were performed in only 44% of institutions. Even the institutions that perform core biopsies only perform them for less than 3% of all FNACs. However, only 5% of institutions performed core biopsies up to three times more than FNAC.

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State of the art of thyroid pathology: FNA diagnostic accuracy in an intermediate center in Ibagué
Daniel Javier Velez Bohorquez, Nohora Bibiana Varon Arce, Sandra Milena Tellez Olaya, Sebastian Camilo Mora Garcia, Anggi Margarita Velez Bohorquez, Mabel Elena Bohorquez Lozano
Universitas Médica.2023;[Epub] CrossRef
The Asian Thyroid Working Group, from 2017 to 2023
Kennichi Kakudo, Chan Kwon Jung, Zhiyan Liu, Mitsuyoshi Hirokawa, Andrey Bychkov, Huy Gia Vuong, Somboon Keelawat, Radhika Srinivasan, Jen-Fan Hang, Chiung-Ru Lai
Journal of Pathology and Translational Medicine.2023; 57(6): 289. CrossRef
Diagnostic value of thyroid imaging reporting and data system combined with BRAFV600E mutation analysis in Bethesda categories III–V thyroid nodules
Liuxi Wu, Hua Shu, Wenqin Chen, Yingqian Gao, Ya Yuan, Xiao Li, Wenjuan Lu, Xinhua Ye, Hongyan Deng
Scientific Reports.2022;[Epub] CrossRef
Contribution of cytologic examination to diagnosis of poorly differentiated thyroid carcinoma
Na Rae Kim, Jae Yeon Seok, Yoo Seung Chung, Joon Hyop Lee, Dong Hae Chung
Journal of Pathology and Translational Medicine.2020; 54(2): 171. CrossRef
Systematic thyroid screening in myotonic dystrophy: link between thyroid volume and insulin resistance
Adrien Ben Hamou, Stéphanie Espiard, Christine Do Cao, Miriam Ladsous, Camille Loyer, Alexandre Moerman, Samuel Boury, Maéva Kyheng, Claire-Marie Dhaenens, Vincent Tiffreau, Pascal Pigny, Gilles Lebuffe, Robert Caiazzo, Sébastien Aubert, Marie Christine V
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The History of Korean Thyroid Pathology
Soon Won Hong, Chan Kwon Jung
International Journal of Thyroidology.2018; 11(1): 15. CrossRef
BRAFV600E Mutation is a Strong Preoperative Indicator for Predicting Malignancy in Thyroid Nodule Patients with Atypia of Undetermined Significance Identified by Fine Needle Aspiration
Hye Rang Choi, Bo-Yoon Choi, Jae Hoon Cho, Young Chang Lim
Korean Journal of Otorhinolaryngology-Head and Neck Surgery.2018; 61(11): 600. 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
Journal of Pathology and Translational Medicine.2018; 52(6): 404. CrossRef
Thyroid FNA cytology in Asian practice—Active surveillance for indeterminate thyroid nodules reduces overtreatment of thyroid carcinomas
K. Kakudo, M. Higuchi, M. Hirokawa, S. Satoh, C. K. Jung, A. Bychkov
Cytopathology.2017; 28(6): 455. CrossRef
The Use of Fine-Needle Aspiration (FNA) Cytology in Patients with Thyroid Nodules in Asia: A Brief Overview of Studies from the Working Group of Asian Thyroid FNA Cytology
Chan Kwon Jung, SoonWon Hong, Andrey Bychkov, Kennichi Kakudo
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Original Articles

The Intraoperative Immunohistochemical Staining of CD56 and CK19 Improves Surgical Decision for Thyroid Follicular Lesions: Ju Yeon Pyo, Sung-eun Choi, Eunah Shin, JaSeung Koo, SoonWon Hong; J Pathol Transl Med. 2017;51(5):463-470. Published online August 2, 2017; DOI: https://doi.org/10.4132/jptm.2017.05.25

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Abstract PDF

Background
When differential diagnosis is difficult in thyroid follicular lesions with overlapping histological features, the immunohistochemical staining can help confirm the diagnosis. We aimed to evaluate the effectiveness of rapid immunohistochemical stains of CD56 and cytokeratin 19 on frozen sections of thyroid follicular lesion and explore the possible gains and limitations of the practice. Methods: Eighty-six nodules of 79 patients whose intraoperative frozen sections were selected as the control group, and 53 nodules of 48 patients whose intraoperative frozen sections were subject to rapid immunohistochemistry were selected as the study group. Results: Five nodules (6%) in the control group were diagnosed as follicular neoplasm and six nodules (7%) were deferred. In the study group, six nodules (11%) were follicular neoplasm and none were deferred. Three nodules (4%) in the control group showed diagnostic discrepancy between the frozen and permanent diagnoses, but none in the study group. The average turnaround time for the frozen diagnosis of the control group was 24 minutes, whereas it was 54 minutes for the study group. Conclusions: Intraoperative rapid immunohistochemical stains significantly decreased the diagnostic discrepancy in this study. Considering the adverse effects of indefinite frozen diagnosis or discrepancy with permanent diagnoses, the intraoperative rapid immunohistochemical stain can help to accurately diagnose and hence provide guidance to surgical treatment.

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High-Contrast Facile Imaging with Target-Directing Fluorescent Molecular Rotors, the N3-Modified Thioflavin T Derivatives
Yuka Kataoka, Hiroto Fujita, Arina Afanaseva, Chioko Nagao, Kenji Mizuguchi, Yuuya Kasahara, Satoshi Obika, Masayasu Kuwahara
Biochemistry.2019; 58(6): 493. CrossRef
The diagnostic value of TROP-2, SLP-2 and CD56 expression in papillary thyroid carcinoma
Xueyang Yang, Yifang Hu, He Shi, Chengzhou Zhang, Zhixiao Wang, Xiaoyun Liu, Huanhuan Chen, Lijuan Zhang, Dai Cui
European Archives of Oto-Rhino-Laryngology.2018; 275(8): 2127. CrossRef

Clinicopathologic Correlations of E-cadherin and Prrx-1 Expression Loss in Hepatocellular Carcinoma: Kijong Yi, Hyunsung Kim, Yumin Chung, Hyein Ahn, Jongmin Sim, Young Chan Wi, Ju Yeon Pyo, Young-Soo Song, Seung Sam Paik, Young-Ha Oh; J Pathol Transl Med. 2016;50(5):327-336. Published online August 31, 2016; DOI: https://doi.org/10.4132/jptm.2016.06.22

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Abstract PDF

Background
Developing predictive markers for hepatocellular carcinoma (HCC) is important, because many patients experience recurrence and metastasis. Epithelial to mesenchymal transition (EMT) is a developmental process that plays an important role during embryogenesis and also during cancer metastasis. Paired-related homeobox protein 1 (Prrx-1) is an EMT inducer that has recently been introduced, and its prognostic significance in HCC is largely unknown.
Methods
Tissue microarray was constructed using surgically resected primary HCCs from 244 cases. Immunohistochemical staining of E-cadherin and Prrx-1 was performed. The correlation between E-cadherin loss and Prrx-1 expression, as well as other clinicopathologic factors, was evaluated.
Results
E-cadherin expression was decreased in 96 cases (39.4%). Loss of E-cadherin correlated with a higher recurrence rate (p < .001) but was not correlated with patient’s survival. Thirty-two cases (13.3%) showed at least focal nuclear Prrx-1 immunoreactivity while all non-neoplastic livers (n = 22) were negative. Prrx-1 expression was not associated with E-cadherin loss, survival or recurrence rates, pathologic factors, or the Ki-67 labeling index. Twenty tumors that were positive for E-cadherin and Prrx-1 had significantly higher nuclear grades than the rest of the cohort (p = .037). In Cox proportional hazard models, E-cadherin loss and large vessel invasion were independent prognostic factors for shorter disease-free survival. Cirrhosis and high Ki-67 index (> 40%) were independent prognostic factors for shorter overall survival.
Conclusions
Prrx-1 was expressed in small portions of HCCs but not in normal livers. Additional studies with a large number of Prrx-1-positive cases are required to confirm the results of this study.

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The Prognostic Importance of Ki-67 in Gastrointestinal Carcinomas: A Meta-analysis and Multi-omics Approach
Mahdieh Razmi, Fatemeh Tajik, Farideh Hashemi, Ayna Yazdanpanah, Fatemeh Hashemi-Niasari, Adeleh Divsalar
Journal of Gastrointestinal Cancer.2024; 55(2): 599. CrossRef
Homotypic cell-in-cell structures as an adverse prognostic predictor of hepatocellular carcinoma
Ruizhi Wang, Yichao Zhu, Hao Zhong, Xinyue Gao, Qiang Sun, Meifang He
Frontiers in Oncology.2022;[Epub] CrossRef
Dysregulated paired related homeobox 1 impacts on hepatocellular carcinoma phenotypes
Weronika Piorońska, Zeribe Chike Nwosu, Mei Han, Michael Büttner, Matthias Philip Ebert, Steven Dooley, Christoph Meyer
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The Expression of Hypoxia Inducible Factor-1alpha and Its Correlation with the Expressions of Cyclin A1 and Cyclin B1 and the Clinicopathologic Factors of Uterine Cervical Carcinoma.: Ju Yeon Pyo, Jae Ho Cho, Hyunki Kim, Jong Pil Park, Young Tae Kim, Nam Hoon Cho; Korean J Pathol. 2009;43(1):13-19.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.1.13

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Abstract PDF: BACKGROUND
Hypoxia inducible factor-1alpha(HIF-1alpha) is a transcription factor for various target genes that are involved in adapting cells to hypoxia. It promotes cell proliferation and survival via modulation of such cell cycle regulators such as cyclin A1 and cyclin B1 in response to hypoxia. This is associated with local failure of radiotherapy, which renders a poor prognosis for cervical carcinoma.
METHODS
Using the tissue histologic sections and a tissue microarray of the archived biopsy and surgical specimens of uterine cervical carcinoma from 57 patients who were treated with radiation therapy alone, we performed immunohistochemical staining for HIF-1alpha and cyclin A1 and B1 to evaluate the correlations between the expressions of these proteins in tumors and the clinicopathologic parameters associated with the prognosis.
RESULTS
The large tumor cell nests and invasive front margins of the tumors showed comparatively intense immunoreactivity of HIF-1alpha. There was no significant correlation between the HIF-1alpha, cyclin A1 and cyclin B1 expressions and the clinicopathologic factors.
CONCLUSIONS
The HIF-1alpha expression showed marked intra-tumoral heterogeneity. The HIF-1alpha expression is neither a powerful predictor of resistance to radiotherapy nor is it a poor prognostic marker in cervical carcinoma patients who are treated with radiotherapy. The expressions of cyclin A1 and cyclin B1 are neither independently associated with the response of radiation therapy nor are they associated with the prognostic parameters of uterine cervical carcinoma.

Comparision of Effectiveness between the ThinPrep(R) and the Cytospin Preparations of the Repeated Urine Cytology.: Soon Won Hong, Hyun Kyung Kim, Ju Yeon Pyo, Yoonhee Lee, Woo Hee Jung, Se Hoon Kim; Korean J Cytopathol. 2007;18(1):55-61.

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Abstract PDF: Once diagnosed as "cell paucity" or "atypia" by the cytospin (CS) preparation, this CS preparation does not secure a precise diagnosis by repeated testing alone. Although the ThinPrep(R) (TP) preparation is acknowledged to show increased cellularity, performing the screening tests for the cases that have enough cellularity, according to CS, raises issues for the cost-effectiveness. To obtain a more precise diagnosis through increasing the cellularity by performing TP, we selected the cases that were diagnosed as "cell paucity" or "atypia" by CS, but they required a more precise diagnosis, and the samples were processed via both CS and TP to compare the results. 11 patients diagnosed as "cell paucity" and 22 patients diagnosed as "atypia" by CS participated in this study. When the detection rate of atypical cells in both preparations with repeated urine cytology was compared, the overall detection rate of TP (16cases, 48.5%) was superior than that of CS (11cases, 33.3%), with statistical significance. The cellularity of both preparations was compared on repeated urine cytology; the general cellularity of TP (29cases, 87.9%) was higher than that of CS (20cases, 60.6%), but there was no statistical significance. Particularly, we repeated the TP for the 1 case that was diagnosed as "atypia" and we performed polyoma virus immunohistochemical staining, which confirmed polyoma virus. In conclusion, we can avoid obtaining negative diagnosis from cases with uncertain "atypia" or "cell paucity" by performing repeated TP testing.

Progressive Suppression of Selenium Binding Protein 1 in Gastric Adenoma and Adenocarcinoma.: Hyunki Kim, Hyun Ju Kang, Jong Pil Park, Ju Yeon Pyo, Hoguen Kim; Korean J Pathol. 2008;42(6):344-350.

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Abstract PDF: BACKGROUND
Human selenium binding protein 1 (SELENBP1) is a protein that binds selenium as a cofactor. The decreased expression of SELENBP1 in several types of carcinomas and its association with a poor prognosis have previously been reported on. In this study, we evaluated the expression of SELENBP1 in low-grade and high-grade epithelial dysplasia/ adenomas and adenocarcinomas. METHODS: We analyzed 45 cases of low-grade epithelial dysplasia/adenomas, 42 cases of high-grade epithelial dysplasia/adenomas and 64 cases of adenocarcinomas and all of them were obtained from endoscopic mucosal resection or endoscopic submucosal dissection. We analyzed all of them for their SELENBP1 expression by immunohistochemistry. Eight triple-paired cases of gastric mucosa, adenoma and adenocarcinoma from the same patient were selected for RT-PCR analysis. RESULTS: There was a progressive decrease in the expression of SELENBP1 from the low-grade dysplasia/adenomas (42/45, 93%) to the high-grade dysplasia/adenomas (29/42, 69%) and finally to the adenocarcinomas (24/64, 37%), (p<0.001). The progressive decrease in the SELENBP1 expression was also evident in the eight paired cases that were analyzed by RT-PCR. CONCLUSIONS: Our findings demonstrate that the SELENBP1 expression is suppressed in gastric epithelial dysplasia/adenomas and adenocarcinomas. The suppression of SELENBP1 was significantly more frequent and severer in the adenocarcinomas than that in the low-grade dysplasia/ adenomas, and this implies that the suppression of SELENBP1 is a late event in gastric carcinogenesis.

Case Report

Solid Variant of Mammary Adenoid Cystic Carcinoma.: Ji Eun Kwon, Yoon Hee Lee, Ju Yeon Pyo, Sang Kyum Kim, Byeong Woo Park, Woo Ick Yang; Korean J Pathol. 2007;41(6):424-426.

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Abstract PDF: Adenoid cystic carcinoma (ACC) is a rare type of breast carcinoma and this tumor makes up less than 0.1% of all mammary carcinomas; ACC is known to show a relatively favorable prognosis. Among a variety of microscopic growth patterns of mammary ACC, a solid variant is the rarest and this can cause diagnostic difficulties. We present here a case of a solid variant of mammary ACC that occurred in the right breast of a 40-year-old woman who was initially diagnosed with invasive ductal carcinoma. We discuss the histological and clinical characteristics of this case.

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