Cancer Research and Treatment

Original Articles

Breast cancer

A Nationwide Study on HER2-Low Breast Cancer in South Korea: Its Incidence of 2022 Real World Data and the Importance of Immunohistochemical Staining Protocols: Min Chong Kim, Eun Yoon Cho, So Yeon Park, Hee Jin Lee, Ji Shin Lee, Jee Yeon Kim, Ho-chang Lee, Jin Ye Yoo, Hee Sung Kim, Bomi Kim, Wan Seop Kim, Nari Shin, Young Hee Maeng, Hun Soo Kim, Sun Young Kwon, Chungyeul Kim, Sun-Young Jun, Gui Young Kwon, Hye Jeong Choi, So Mang Lee, Ji Eun Choi, Ae Ri An, Hyun Joo Choi, EunKyung Kim, Ahrong Kim, Ji-Young Kim, Jeong Yun Shim, Gyungyub Gong, Young Kyung Bae; Cancer Res Treat. 2024;56(4):1096-1104. Published online March 6, 2024; DOI: https://doi.org/10.4143/crt.2024.092

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Purpose
Notable effectiveness of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer (BC) has focused pathologists’ attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results.
Materials and Methods
The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected.
Results
Total 11,416 patients from 25 institutions included in this study. Of these patients, 40.7% (range, 6.0% to 76.3%) were classified as HER2-zero, 41.7% (range, 10.5% to 69.1%) as HER2-low, and 17.5% (range, 6.7% to 34.0%) as HER2-positive. HER2-low tumors were associated with positive estrogen receptor and progesterone receptor statuses (p < 0.001 and p < 0.001, respectively). Antigen retrieval times (≥ 36 minutes vs. < 36 minutes) and antibody incubation times (≥ 12 minutes vs. < 12 minutes) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3,259) of the patients.
Conclusion
The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

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Impact of immunohistochemistry staining conditions on the incidence of human epidermal growth factor receptor 2 (HER2)-low breast cancer
Min Chong Kim, Sun Young Kwon, Hye Ra Jung, Young Kyung Bae
Virchows Archiv.2024; 485(6): 1117. CrossRef
Breast Cancer: Extracellular Matrix and Microbiome Interactions
Lourdes Herrera-Quintana, Héctor Vázquez-Lorente, Julio Plaza-Diaz
International Journal of Molecular Sciences.2024; 25(13): 7226. CrossRef

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Expression of Myxovirus Resistance A (MxA) Is Associated with Tumor-Infiltrating Lymphocytes in Human Epidermal Growth Factor Receptor 2 (HER2)–Positive Breast Cancers: So Jeong Lee, Cheong-Soo Hwang, Young-Keum Kim, Hyun Jung Lee, Sang-Jeong Ahn, Nari Shin, Jung Hee Lee, Dong Hoon Shin, Kyung Un Choi, Do Youn Park, Chang Hun Lee, Gi Young Huh, Mi Young Sol, Hee Jin Lee, Gyungyub Gong, Jee Yeon Kim, Ahrong Kim; Cancer Res Treat. 2017;49(2):313-321. Published online July 7, 2016; DOI: https://doi.org/10.4143/crt.2016.098

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Purpose
The prognostic significance of tumor-infiltrating lymphocytes (TILs) has been determined in breast cancers. Interferons can affect T-cell activity through direct and indirect mechanisms. Myxovirus resistance A (MxA) is an excellent marker of interferon activity. Here,we evaluated TILs and MxA expression in human epidermal growth factor receptor 2 (HER2)–positive breast cancers.
Materials and Methods
Ninety cases of hormone receptor (HR)+/HER2+ tumors and 78 cases of HR–/HER2+ tumors were included. The TILs level was assessed using hematoxylin and eosin–stained full face sections, and MxA expressionwas evaluated by immunohistochemistrywith a tissue microarray.
Results
MxA protein expression was significantly higher in tumors with high histologic grade (p=0.023) and high levels of TILs (p=0.002). High levels of TILs were correlated with high histological grade (p=0.001), negative lymphovascular invasion (p=0.007), negative lymph node metastasis (p=0.007), absence of HR expression (p < 0.001), abundant tertiary lymphoid structures (TLSs) around ductal carcinoma in situ (p=0.018), and abundant TLSs around the invasive component (p < 0.001). High levels of TILs were also associated with improved disease-free survival, particularly in HR–/HER2+ breast cancers. However, MxA was not a prognostic factor.
Conclusion
High expression of MxA in tumor cells was associated with high levels of TILs in HER2-positive breast cancers. Additionally, a high level of TILs was a prognostic factor for breast cancer, whereas the level of MxA expression had no prognostic value.

Citations

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Multi-resolution deep learning characterizes tertiary lymphoid structures and their prognostic relevance in solid tumors
Mart van Rijthoven, Simon Obahor, Fabio Pagliarulo, Maries van den Broek, Peter Schraml, Holger Moch, Jeroen van der Laak, Francesco Ciompi, Karina Silina
Communications Medicine.2024;[Epub] CrossRef
The roles of tertiary lymphoid structures in chronic diseases
Yuki Sato, Karina Silina, Maries van den Broek, Kiyoshi Hirahara, Motoko Yanagita
Nature Reviews Nephrology.2023; 19(8): 525. CrossRef
NFIC1 suppresses migration and invasion of breast cancer cells through interferon-mediated Jak-STAT pathway
Jing Zhang, Mingyue Fan, Chanjuan Jin, Zhaoying Wang, Yutong Yao, Yueru Shi, Xin Hu, Youzhong Wan
Archives of Biochemistry and Biophysics.2022; 727: 109346. CrossRef
Low MxA Expression Predicts Better Immunotherapeutic Outcomes in Glioblastoma Patients Receiving Heat Shock Protein Peptide Complex 96 Vaccination
Yi Wang, Chunzhao Li, Xiaohan Chi, Xijian Huang, Hua Gao, Nan Ji, Yang Zhang
Frontiers in Oncology.2022;[Epub] CrossRef
Myxovirus resistance 1 (MX1) is an independent predictor of poor outcome in invasive breast cancer
Abrar I. Aljohani, Chitra Joseph, Sasagu Kurozumi, Omar J. Mohammed, Islam M. Miligy, Andrew R. Green, Emad A. Rakha
Breast Cancer Research and Treatment.2020; 181(3): 541. CrossRef
Expression of Immunoproteasome Subunit LMP7 in Breast Cancer and Its Association with Immune-Related Markers
Miseon Lee, In Hye Song, Sun-Hee Heo, Young-Ae Kim, In Ah Park, Won Seon Bang, Hye Seon Park, Gyungyub Gong, Hee Jin Lee
Cancer Research and Treatment.2019; 51(1): 80. CrossRef
Grade II/III Glioma Microenvironment Mining and Its Prognostic Merit
Jiawei Chen, Chongxian Hou, Peng Wang, Yong Yang, Dong Zhou
World Neurosurgery.2019; 132: e76. CrossRef
Programmed death-ligand 1 (PD-L1) expression in tumour cell and tumour infiltrating lymphocytes of HER2-positive breast cancer and its prognostic value
Ahrong Kim, So Jeong Lee, Young Keum Kim, Won Young Park, Do Youn Park, Jee Yeon Kim, Chang Hun Lee, Gyungyub Gong, Gi Yeong Huh, Kyung Un Choi
Scientific Reports.2017;[Epub] CrossRef

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Type IV Collagen and E-cadherin Expression of Progressive Uterine Cervical Epithelial Lesions: Mee Young Sol, Jee Yeon Kim; J Korean Cancer Assoc. 1997;29(4):681-689.

Abstract PDF: PURPOSE
This study was designed to evaluate the role and the value as progression markers, of type IV collagen and E-cadherin in the pathogenesis of progressive uterine cervical epithelial lesions.
MATERIALS AND METHODS
Materials examined were 4 cases of normal exocervical squamous epithelium, 9 of endocervical squamous metaplasias, 2 of mild dysplasias, 8 of moderate dysplasias, 15 of severe dysplasias, 12 of carcinoma in situ, 7 of microinvasive squamous cell carcinomas, and 4 cases of invasive squamous cell carcinomas. All of them were biopsied ones and products of conization and hysterectomy. The expression of type IV collagen and E-cadherin in uterine cervical epithelial lesions were studied by immunohistochemical method using monoclonal antibodies to type IV collagen and E-cadherin.
RESULTS
The expression of type IV collagen decreased relatively stepwise from squamous metaplasias to cervical intraepithelial neoplasias (CIN) and subsequently to invasive carcinomas. The expression of type IV collagen in normal uterine exocervical squamous epithelium was within normal range in contrast to variable expression in squamous metaplasia. There was no definite difference in expression pattern between early invasive carcinoma and advanced invasive carcinomas. Normal and squamous metaplastic epithelium of uterine cervix revealed membranous expression of E-cadherin and cervical intraepithelial lesions showed cytoplasmic expression or negative expression instead of membranous expression. There was clearcut difference in E-cadherin expression between normal or metaplastic epithelium and neoplastic lesions.
CONCLUSION
The change of type IV collagen expression could be an early marker in the progression of uterine cervical epithelial lesions from normal epithelium. And the loss of differentiaton and polarity and the deranged expression of E-cadherin are closely correlated on the basis of the result that the changed expression of E-cadherin was evident in the stage of transition from normal to neoplastic lesions.

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