Journal of Pathology and Translational Medicine

Original Articles

Prevalence of HER2-ultralow breast cancer in South Korea: a multicenter study by reassessment of HER2-zero cases: Min Chong Kim, Eun Yoon Cho, Hee Jin Lee, Ji Shin Lee, Jee Yeon Kim, Wan Seop Kim, Chungyeul Kim, Sun-Young Jun, Hye Jeong Choi, So Mang Lee, Ahrong Kim, Ji-Young Kim, Jeong Yun Shim, Gyungyub Gong, Young Kyung Bae; Received September 17, 2025 Accepted October 21, 2025 Published online February 23, 2026; DOI: https://doi.org/10.4132/jptm.2025.10.22 [Epub ahead of print]

370 View
17 Download

Abstract PDF Supplementary Material: Background
This study aimed to determine the prevalence of human epidermal growth factor receptor 2 (HER2)–ultralow breast cancer among cases initially classified as HER2 immunohistochemistry (IHC) 0 and assess interobserver variability in interpreting low-level HER2 expression. Methods: In this multicenter retrospective study, all invasive breast cancer cases diagnosed between January and December 2022 across 10 Korean institutions were retrieved. Institutional pathologists reexamined HER2 IHC slides originally reported as IHC 0 according to the 2018 American Society of Clinical Oncology/College of American Pathologists guidelines and reclassified them as HER2-null (0), HER2-ultralow (0+), or HER2-low (1+). Slides from 10% of HER2-null and HER2-ultralow cases were digitized for central review and independently assessed by two pathologists, with discrepancies resolved by consensus. Results: Among 8,026 cases, 2,836 cases (35.5%) were initially reported as IHC 0. Upon re-review, 1,673 (59.0%), 1,139 (40.2%), and 24 (0.8%) cases were reclassified as HER2-null, HER2-ultralow, and HER2-low, respectively. The prevalence of HER2-ultralow breast cancer varied considerably across institutions (23.7%–78.1%). Central review of 268 digitized cases showed concordance in 193 cases (72.0%). Among the 75 discordant cases, 54 tumors (72.0%) were upgraded from HER2-null to HER2-ultralow, and 18 (24.0%) tumors were upgraded from HER2-ultralow to HER2-low. Furthermore, two tumors (2.7%) were downgraded from HER2-ultralow to HER2-null. Conclusions: Approximately 40% of cases initially categorized as IHC 0 were reclassified as HER2-ultralow. The substantial inter-institutional variability observed in interpreting low-level HER2 expression highlights the need for standardized training and quality assurance to ensure accurate identification of patients eligible for HER2-targeted antibody–drug conjugates.

Interobserver Variability of Ki-67 Measurement in Breast Cancer: Yul Ri Chung, Min Hye Jang, So Yeon Park, Gyungyub Gong, Woo-Hee Jung, The Korean Breast Pathology Ki- Study Group; J Pathol Transl Med. 2016;50(2):129-137. Published online February 15, 2016; DOI: https://doi.org/10.4132/jptm.2015.12.24

13,287 View
131 Download
29 Web of Science
30 Crossref

Background
As measurement of Ki-67 proliferation index is an important part of breast cancer diagnostics, we conducted a multicenter study to examine the degree of concordance in Ki-67 counting and to find factors that lead to its variability. Methods: Thirty observers from thirty different institutions reviewed Ki-67–stained slides of 20 different breast cancers on whole sections and tissue microarray (TMA) by online system. Ten of the 20 breast cancers had hot spots of Ki-67 expression. Each observer scored Ki-67 in two different ways: direct counting (average vs. hot spot method) and categorical estimation. Intraclass correlation coefficient (ICC) of Ki-67 index was calculated for comparative analysis. Results: For direct counting, ICC of TMA was slightly higher than that of whole sections using average method (0.895 vs 0.858). The ICC of tumors with hot spots was lower than that of tumors without (0.736 vs 0.874). In tumors with hot spots, observers took an additional counting from the hot spot; the ICC of whole sections using hot spot method was still lower than that of TMA (0.737 vs 0.895). In categorical estimation, Ki-67 index showed a wide distribution in some cases. Nevertheless, in tumors with hot spots, the range of distribution in Ki-67 categories was decreased with hot spot method and in TMA platform. Conclusions: Interobserver variability of Ki-67 index for direct counting and categorical estimation was relatively high. Tumors with hot spots showed greater interobserver variability as opposed to those without, and restricting the measurement area yielded lower interobserver variability.

Citations

Citations to this article as recorded by

Dynamic biomarkers in hormone receptor-positive/HER2-negative breast cancer trials: a new hope for precision oncology
Giuseppe Di Grazia, Rodrigo Sánchez-Bayona, Climent Casals-Pascual, Tomás Pascual, Daniele Generali, Alessandra Gennari, Paolo Vigneri, Nadia Harbeck, Javier Cortés, Aleix Prat, Francesco Schettini
npj Breast Cancer.2026;[Epub] CrossRef
Comparative analysis of Ki-67 labeling index morphometry using deep learning, conventional image analysis, and manual counting
Mohammad Rizwan Alam, Kyung Jin Seo, Kwangil Yim, Phoebe Liang, Joe Yeh, Chifu Chang, Yosep Chong
Translational Oncology.2025; 51: 102159. CrossRef
Machine Learning-Based Approaches for Breast Density Estimation from Mammograms: A Comprehensive Review
Khaldoon Alhusari, Salam Dhou
Journal of Imaging.2025; 11(2): 38. CrossRef
Letter re: A critical appraisal of the DATA trial analysis on the prognostic and predictive value of the luminal-like subtype
M. Rizk, K. Mokbel
ESMO Open.2025; 10(5): 105067. CrossRef
Clinico-Histomorphological and Mib-1 Analysis of Recurrent Meningiomas: A Retrospective Study
Sujata Sarangi, Asha Shenoy, Ashvini Kolhe, Kanchan Kothari
Asian Journal of Neurosurgery.2025; 20(04): 785. CrossRef
Emerging Diagnostics and Therapies in Neuroendocrine Neoplasms: A Critical Review
Jorge H. Hernandez-Felix, Monica Isabel Meneses-Medina, Rachel Riechelmann, Jonathan Strosberg, Rocio Garcia-Carbonero, Jaydira del Rivero
Cancers.2025; 17(22): 3632. CrossRef
Ki-67 Testing in Breast Cancer: Assessing Variability With Scoring Methods and Specimen Types and the Potential Subsequent Impact on Therapy Eligibility
Therese Bocklage, Virgilius Cornea, Caylin Hickey, Justin Miller, Jessica Moss, Mara Chambers, S. Emily Bachert
Applied Immunohistochemistry & Molecular Morphology.2024; 32(3): 119. CrossRef
Interobserver agreement and diagnostic challenges of Congo red staining for amyloid detection on fat pad aspiration biopsies
Levent Trabzonlu, T. Leif Helland, Melanie C. Kwan, Nathalie Kumiega, M. Lisa Zhang, Ivan Chebib, Vanda F. Torous
Journal of the American Society of Cytopathology.2024; 13(5): 359. CrossRef
Assessment of the Predictive Role of Ki-67 in Breast Cancer Patients’ Responses to Neoadjuvant Chemotherapy
Ghizlane Rais, Rania Mokfi, Farah Boutaggount, Meryem Maskrout, Soundouss Bennour, Chaymae Senoussi, Fadoua Rais
European Journal of Breast Health.2024; : 199. CrossRef
Improving the accuracy of reporting Ki-67 IHC by using an AI tool
Sahil Ajit Saraf, Aahan Singh, Wai Po Kevin Teng, Sencer Karakaya, M. Logaswari, Kaveh Taghipour, Rajasa Jialdasani, Li Yan Khor, Kiat Hon Lim, Sathiyamoorthy Selvarajan, Vani Ravikumar, Md Ali Osama, Priti Chatterjee, Santosh KV
Heliyon.2024; 10(22): e40193. CrossRef
Predictive Value of Ki-67 Index in Evaluating Sporadic Vestibular Schwannoma Recurrence: Systematic Review and Meta-analysis
Kunal Vakharia, Hirotaka Hasegawa, Christopher Graffeo, Mohammad H. A. Noureldine, Salomon Cohen-Cohen, Avital Perry, Matthew L. Carlson, Colin L. W. Driscoll, Maria Peris-Celda, Jamie J. Van Gompel, Michael J. Link
Journal of Neurological Surgery Part B: Skull Base.2023; 84(02): 119. CrossRef
Venous invasion and lymphatic invasion are correlated with the postoperative prognosis of pancreatic neuroendocrine neoplasm
Sho Kiritani, Junichi Arita, Yuichiro Mihara, Rihito Nagata, Akihiko Ichida, Yoshikuni Kawaguchi, Takeaki Ishizawa, Nobuhisa Akamatsu, Junichi Kaneko, Kiyoshi Hasegawa
Surgery.2023; 173(2): 365. CrossRef
Automated Molecular Subtyping of Breast Carcinoma Using Deep Learning Techniques
S. Niyas, Ramya Bygari, Rachita Naik, Bhavishya Viswanath, Dhananjay Ugwekar, Tojo Mathew, J Kavya, Jyoti R Kini, Jeny Rajan
IEEE Journal of Translational Engineering in Health and Medicine.2023; 11: 161. CrossRef
Grade Progression and Intrapatient Tumor Heterogeneity as Potential Contributors to Resistance in Gastroenteropancreatic Neuroendocrine Tumors
Diana Grace Varghese, Jaydira Del Rivero, Emily Bergsland
Cancers.2023; 15(14): 3712. CrossRef
Diagnostic Role and Prognostic Impact of PSAP Immunohistochemistry: A Tissue Microarray Study on 31,358 Cancer Tissues
Laura Sophie Tribian, Maximilian Lennartz, Doris Höflmayer, Noémi de Wispelaere, Sebastian Dwertmann Rico, Clara von Bargen, Simon Kind, Viktor Reiswich, Florian Viehweger, Florian Lutz, Veit Bertram, Christoph Fraune, Natalia Gorbokon, Sören Weidemann, C
Diagnostics.2023; 13(20): 3242. CrossRef
AI-Powered Segmentation of Invasive Carcinoma Regions in Breast Cancer Immunohistochemical Whole-Slide Images
Yiqing Liu, Tiantian Zhen, Yuqiu Fu, Yizhi Wang, Yonghong He, Anjia Han, Huijuan Shi
Cancers.2023; 16(1): 167. CrossRef
Expression of estrogen and progesterone receptors, HER2 protein and Ki-67 proliferation index in breast carcinoma in both tumor tissue and tissue microarray
UP Hacısalihoğlu, MA Dogan
Biotechnic & Histochemistry.2022; 97(4): 298. CrossRef
Diffusive Ki67 and vimentin are associated with worse recurrence-free survival of upper tract urothelial carcinoma: A retrospective cohort study from bench to bedside
Che Hsueh Yang, Wei Chun Weng, Yen Chuan Ou, Yi Sheng Lin, Li Hua Huang, Chin Heng Lu, Tang Yi Tsao, Chao Yu Hsu, Min Che Tung
Urologic Oncology: Seminars and Original Investigations.2022; 40(3): 109.e21. CrossRef
Should Ki-67 be adopted to select breast cancer patients for treatment with adjuvant abemaciclib?
P. Tarantino, H.J. Burstein, N.U. Lin, I.E. Krop, E.P. Winer, S.J. Schnitt, E.P. Hamilton, S.A. Hurvitz, H.S. Rugo, G. Curigliano, S.M. Tolaney
Annals of Oncology.2022; 33(3): 234. CrossRef
A novel deep classifier framework for automated molecular subtyping of breast carcinoma using immunohistochemistry image analysis
Tojo Mathew, S. Niyas, C.I. Johnpaul, Jyoti R. Kini, Jeny Rajan
Biomedical Signal Processing and Control.2022; 76: 103657. CrossRef
Deep learning for the standardized classification of Ki-67 in vulva carcinoma: A feasibility study
Matthias Choschzick, Mariam Alyahiaoui, Alexander Ciritsis, Cristina Rossi, André Gut, Patryk Hejduk, Andreas Boss
Heliyon.2021; 7(7): e07577. CrossRef
Oncotype DX Predictive Nomogram for Recurrence Score Output: The Novel System ADAPTED01 Based on Quantitative Immunochemistry Analysis
Fabio Marazzi, Roberto Barone, Valeria Masiello, Valentina Magri, Antonino Mulè, Angela Santoro, Federica Cacciatori, Luca Boldrini, Gianluca Franceschini, Francesca Moschella, Giuseppe Naso, Silverio Tomao, Maria Antonietta Gambacorta, Giovanna Mantini,
Clinical Breast Cancer.2020; 20(5): e600. CrossRef
Study of Ki-67 index in the molecular subtypes of breast cancer: Inter-observer variability and automated scoring
Divya Meermira, Meenakshi Swain, Swarnalata Gowrishankar
Indian Journal of Cancer.2020; 57(3): 289. CrossRef
Improving the accuracy of gastrointestinal neuroendocrine tumor grading with deep learning
Darshana Govind, Kuang-Yu Jen, Karen Matsukuma, Guofeng Gao, Kristin A. Olson, Dorina Gui, Gregory. E. Wilding, Samuel P. Border, Pinaki Sarder
Scientific Reports.2020;[Epub] CrossRef
Practical approaches to automated digital image analysis of Ki-67 labeling index in 997 breast carcinomas and causes of discordance with visual assessment
Ah-Young Kwon, Ha Young Park, Jiyeon Hyeon, Seok Jin Nam, Seok Won Kim, Jeong Eon Lee, Jong-Han Yu, Se Kyung Lee, Soo Youn Cho, Eun Yoon Cho, Irina V. Lebedeva
PLOS ONE.2019; 14(2): e0212309. CrossRef
Evaluation of Ki-67 Index in Core Needle Biopsies and Matched Breast Cancer Surgical Specimens
Soomin Ahn, Junghye Lee, Min-Sun Cho, Sanghui Park, Sun Hee Sung
Archives of Pathology & Laboratory Medicine.2018; 142(3): 364. CrossRef
Assessment of Ki-67 for Predicting Effective Prognosis in Breast Cancer Subtypes
Sangjung Park, Sunyoung Park, Jungho Kim, Sungwoo Ahn, Kwang Hwa Park, Hyeyoung Lee
Biomedical Science Letters.2018; 24(1): 9. CrossRef
Quantitative tumor heterogeneity assessment on a nuclear population basis
Anne‐Sofie Wessel Lindberg, Knut Conradsen, Rasmus Larsen, Michael Friis Lippert, Rasmus Røge, Mogens Vyberg
Cytometry Part A.2017; 91(6): 574. CrossRef
A comparison of Ki-67 counting methods in luminal Breast Cancer: The Average Method vs. the Hot Spot Method
Min Hye Jang, Hyun Jung Kim, Yul Ri Chung, Yangkyu Lee, So Yeon Park, William B. Coleman
PLOS ONE.2017; 12(2): e0172031. CrossRef
A Novel Breast Cancer Index for Prediction of Distant Recurrence in HR+ Early-Stage Breast Cancer with One to Three Positive Nodes
Yi Zhang, Brock E. Schroeder, Piiha-Lotta Jerevall, Amy Ly, Hannah Nolan, Catherine A. Schnabel, Dennis C. Sgroi
Clinical Cancer Research.2017; 23(23): 7217. CrossRef

Early Colorectal Epithelial Neoplasm in Korea: A Multicenter Survey of Pathologic Diagnosis: Yun Kyung Kang, So-Young Jin, Mee Soo Chang, Jung Yeon Kim, Gyeong Hoon Kang, Hye Seung Lee, Jin Hee Sohn, Ho Sung Park, Kye Won Kwon, Mi Jin Gu, Young Hee Maeng, Jong Eun Joo, Haeng Ji Kang, Hee Kyung Kim, Kee-Taek Jang, Mi Ja Lee, Hee Kyung Chang, Joon Mee Kim, Hye Seung Han, Won Ae Lee, Yoon Jung Choi, Dong Wook Kang, Sunhoo Park, Jae Hyuk Lee, Mee-Yon Cho; Korean J Pathol. 2013;47(3):245-251. Published online June 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.3.245

11,653 View
56 Download
1 Crossref

Abstract PDF

Background

The incidence of early colorectal epithelial neoplasm (ECEN) is increasing, and its pathologic diagnosis is important for patient care. We investigated the incidence of ECEN and the current status of its pathologic diagnosis.

Methods

We collected datasheets from 25 institutes in Korea for the incidence of colorectal adenoma with high grade dysplasia (HGD) and low grade dysplasia in years 2005, 2007, and 2009; and early colorectal carcinoma in the year 2009. We also surveyed the diagnostic terminology of ECEN currently used by the participating pathologists.

Results

The average percentage of diagnoses of adenoma HGD was 7.0%, 5.0%, and 3.4% in years 2005, 2007, and 2009, respectively. The range of incidence rates of adenoma HGD across the participating institutes has gradually narrowed over the years 2005 to 2009. The incidence rate of early colorectal carcinoma in the year 2009 was 21.2%. The participants did not share a single criterion or terminology for the diagnosis of adenoma HGD. The majority accepted the diagnostic terms that distinguished noninvasive, mucosal confined, and submucosal invasive carcinoma.

Conclusions

Further research requirements suggested are a diagnostic consensus for the histopathologic diagnosis of ECEN; and standardization of diagnostic terminology critical for determining the disease code.

Citations

Citations to this article as recorded by

Diminutive and Small Colorectal Polyps: The Pathologist's Perspective
Yun Kyung Kang
Clinical Endoscopy.2014; 47(5): 404. CrossRef

First
Prev
Page of 1
Next
Last

Search