Claudin-Low Breast Cancer; a Molecular Subtype Associated with Poor Prognosis
Kay Dias, Sameer Parpia, Greg Pond, Mark N Levine, Timothy Whelan, Anita L Bane. McMaster Univeristy, Hamilton, ON, Canada; McMaster University, Hamilton, ON, Canada
Background: Molecular profiling of human breast cancers has defined 5 molecular subtypes; luminal A, luminal B, HER2 over-expressing, basal-like and claudin-low. The claudin-low subtype was identified in 2007 and is characterized by low expression of claudins 3, 4, & 7 and E-cadherin. This subtype has been reported to be associated with expression of mesenchymal and cancer stem cell (CSC) markers. Herein we describe the morphological characteristics of claudin-low breast cancers and their association with overall survival and CSC markers.
Design: 943 T1 and T2, lymph node negative, primary invasive breast cancers treated with breast conserving surgery (BCS) and adjuvant radiation had formalin fixed paraffin embedded (FFPE) tumor blocks available for tissue microarray (TMA) construction. On the basis of IHC expression of ER, PR, HER2, Ki67, EGFR, CK5/6, Claudins 3, 4 & 7 and E-cadherin the tumors were classified as luminal A, luminal B, HER2 over-expressing, basal-like or claudin-low. Kaplan-Meier methods were used to estimate overall survival. Fisher's exact tests were used to compare the claudin-low with luminal A subtypes with respect to tumor characteristics and the expression of CSC markers (ALDH1, CD44hi/CD24low).
Results: A molecular subtype was assignable in 782 of 943 tumors (83.0%), of which 357 (46%) were luminal A, 222 (28%) were luminal B, 32 (4%) were HER2 over-expressing, 110 (14%) were basal-like and 61 (8%) were claudin-low. The overall survival for claudin-low tumors at a median follow-up of 12 years was 73.6% (95% confidence interval [CI]: 58.0% to 84.2%) similar to that of basal-like (74.1%) and HER2 (72.5%) over-expressing subtypes. Compared to luminal A type tumors the claudin-low subtype were statistically more likely to have circumscribed tumor margins (20% vs 9%, p=0.022). There was no statistically significant association between claudin-low subtype and the expression of CSC markers (ALDH1 p= 1.00, CD44hi/CD24low p=0.23).
Conclusions: The claudin-low subtype represents a minority of invasive breast cancers (8%), this group is characterized by poor prognosis similar to that of HER2 over-expressing and basal-like tumors. No association with the breast CSC markers examined was demonstrable in this cohort.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 55, Wednesday Morning