Reduced Expression of TGF-Beta Receptor III Is a Specific Event in Triple Negative Breast Carcinomas
Nilam Virani, Celina Kleer. University of Michigan, Ann Arbor, MI
Background: TGF-β receptor III (TBR3) is a member of the TGF-beta signaling pathways, with functions in cell proliferation and migration in many human tissues, including regulation of breast carcinogenesis. However, the specific role of TBR3 is poorly understood and has not yet been extensively studied. Recent studies propose that it may function as a tumor suppressor, based on the observation that loss of TBR3 correlates with disease progression.
Design: Tissue microarrays (TMAs) were used from primary breast carcinomas in 203 female patients. Three separate cores represented each case. Sections were stained with a rabbit polyclonal anti-TBR3 antibody and evaluated for intensity of reactivity based on a previously validated scoring system (1 to 4, TBR3 low= scores 1-2; TBR3 high= scores 3-4).
Results: Of the 203 invasive carcinomas, 103 were luminal A, 25 luminal B, 9 HER2, and 64 triple negative (TN). TBR3 was high in 109 (54%) and low in 94 (46%) cases. Low TBR3 was statistically significantly associated with the TN subtype. TBR3 was low in 61 (95%) and high in 3 (5%) of 64 TN carcinomas. The opposite was observed in luminal A tumors, where TBR3 was high 80 (78%), and low in 23 (22%) tumors. In luminal A tumors low TBR3 was statistically significantly associated with high histological grade. TBR3 was not associated with HER2 or LB subtypes.
Conclusions: We discovered a significant association between loss or reduction of TBR3 expression and TN breast cancers. We also identified that TBR3 is reduced in a subset of luminal A tumors where it is associated with high histological grade. These data suggest that TBR3 loss might be causally involved in the development of TN breast cancers, and warrant further investigation.
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 12, Tuesday Morning