Sewha Kim1, Byung-In Moon2, Woosung Lim2, Sanghui Park3, Min Sun Cho3, Sun Hee Sung4. 1. Department of Pathology, CHA Bundang Medical Center, CHA University, Bundang-gu, Seongnam-si, Gyeonggi-do, Korea. 2. Department of Surgery, Ewha Womans University School of Medicine, Yangcheon-gu, Seoul, Korea. 3. Department of Pathology, Ewha Womans University School of Medicine, Yangcheongu, Seoul, Korea. 4. Department of Pathology, Ewha Womans University School of Medicine, Yangcheongu, Seoul, Korea. Electronic address: sunhsung@ewha.ac.kr.
Abstract
INTRODUCTION: Recently, Burstein et al identified 4 stable molecular subtypes of triple negative breast cancer (TNBC) by mRNA profiling: luminal androgen receptor (LAR), mesenchymal (MES), basal-like immune-activated (BLIA), and basal-like immune-suppressive (BLIS) types. The purpose of this study was to assess the feasibility of immunohistochemistry (IHC) surrogate panel in classifying the TNBC molecular subtypes using a large cohort of TNBC retrieved from a single institution. MATERIALS AND METHODS: IHC for androgen receptor [AR], claudin-3, E-cadherin, cytokeratin 5/6 [CK5/6], epidermal growth factor receptor [EGFR], indoleamine 2,3-dioxygenase 1 [IDO1], and Forkhead box C1 [FOXC1] were performed using the tissue microarray constructed from 200 TNBC samples. RESULTS: The 200 TNBCs were classified as LAR (AR+, n = 22; 11.0%), MES (claudin 3- and/or E-cadherin-, n = 23; 11.5%), basal-like (CK5/6+ and/or EGFR+, n = 85; 42.5%), mixed (n = 60; 30%), and unclassifiable type (n = 10; 5%). LAR type was associated with older patient age, apocrine histologic features, low density of stromal tumor-infiltrating lymphocytes (TIL), and low Ki-67 labeling index. MES type was associated with tumor cell discohesiveness and metaplastic features. Basal-like type was associated with younger patient age, high histologic grade, high stromal TIL density, and high Ki-67 labeling index. Basal-like TNBCs were further classified as BLIA (IDO1+ and FOXC1-, n = 27) or BLIS type (IDO1- and FOXC1+, n = 11). BLIS type was associated with large tumor size and low stromal TIL density, which had the worst prognostic outcome among 4 subtypes. CONCLUSION: The IHC surrogate panel may define TNBC subtypes with distinct clinicopathologic characteristics and prognostic significance.
INTRODUCTION: Recently, Burstein et al identified 4 stable molecular subtypes of triple negative breast cancer (TNBC) by mRNA profiling: luminal androgen receptor (LAR), mesenchymal (MES), basal-like immune-activated (BLIA), and basal-like immune-suppressive (BLIS) types. The purpose of this study was to assess the feasibility of immunohistochemistry (IHC) surrogate panel in classifying the TNBC molecular subtypes using a large cohort of TNBC retrieved from a single institution. MATERIALS AND METHODS: IHC for androgen receptor [AR], claudin-3, E-cadherin, cytokeratin 5/6 [CK5/6], epidermal growth factor receptor [EGFR], indoleamine 2,3-dioxygenase 1 [IDO1], and Forkhead box C1 [FOXC1] were performed using the tissue microarray constructed from 200 TNBC samples. RESULTS: The 200 TNBCs were classified as LAR (AR+, n = 22; 11.0%), MES (claudin 3- and/or E-cadherin-, n = 23; 11.5%), basal-like (CK5/6+ and/or EGFR+, n = 85; 42.5%), mixed (n = 60; 30%), and unclassifiable type (n = 10; 5%). LAR type was associated with older patient age, apocrine histologic features, low density of stromal tumor-infiltrating lymphocytes (TIL), and low Ki-67 labeling index. MES type was associated with tumor cell discohesiveness and metaplastic features. Basal-like type was associated with younger patient age, high histologic grade, high stromal TIL density, and high Ki-67 labeling index. Basal-like TNBCs were further classified as BLIA (IDO1+ and FOXC1-, n = 27) or BLIS type (IDO1- and FOXC1+, n = 11). BLIS type was associated with large tumor size and low stromal TIL density, which had the worst prognostic outcome among 4 subtypes. CONCLUSION: The IHC surrogate panel may define TNBC subtypes with distinct clinicopathologic characteristics and prognostic significance.
Authors: Jessica C Casciano; Caroline Perry; Adam J Cohen-Nowak; Katelyn D Miller; Johan Vande Voorde; Qifeng Zhang; Susan Chalmers; Mairi E Sandison; Qin Liu; Ann Hedley; Tony McBryan; Hsin-Yao Tang; Nicole Gorman; Thomas Beer; David W Speicher; Peter D Adams; Xuefeng Liu; Richard Schlegel; John G McCarron; Michael J O Wakelam; Eyal Gottlieb; Andrew V Kossenkov; Zachary T Schug Journal: Br J Cancer Date: 2020-01-16 Impact factor: 7.640