Analysis of Class III Beta Tubulin by Molecular Subtype in Breast Cancer – A Pilot Study.
Yihong Wang, Joseph Sparano, Jaya Sunkara, Susan Horwitz, Hayley McDaid. Albert Einstein College of Medicine, Bronx, NY
Background: Class III beta tubulin (βΙΙΙ-tubulin) is expressed normally in tissues of neuronal lineage and in human malignancies, including non-small cell lung cancer, ovarian, gastric, pancreatic and breast cancers. Aberrant overexpression of βIII-tubulin in these tumors is associated with unfavorable outcome and resistance to chemotherapy regimens. Prior studies that examined tubulin isotypes in advanced breast cancer indicated that increased βΙΙΙ-tubulin expression was associated with resistance to docetaxel, but did not evaluate the relationship between βΙΙΙ-tubulin expression and breast cancer subtypes. In this analysis, we evaluated patterns of βΙΙΙ-tubulin expression by breast cancer subtypes.
Design: βΙΙΙ-tubulin antibody (Clone TUJ1, dilution 1:500, Covance, Emeryville, CA) was used to evaluate 50 randomly selected cases including 17 luminal A (ER/PR+, Her2 0-1+ by IHC), 7 luminal B (ER/PR+, Her2 3+ by IHC), 6 Her2 enriched (ER/PR-, Her2 3+ by IHC), and 20 basal-like breast cancers (ER/PR-, Her2 0-1+ by IHC). Immunohistochemistry for βΙΙΙ-tubulin was scored by one of the co-authors (YW) by assigning a percentage which represented the estimated proportion of positive-staining tumor cells and an intensity score which represented the average intensity of positive tumor cells (0, none; 1, weak; 2 intermediate; 3, strong). Overexpression was defined as an intensity score of 3 occurring in more than 30% of tumor cells.
Results: βΙΙΙ-tubulin overexpression was present in 22/50 (44%) cases, including 0/7 (0%) grade I, 4/15 (27%) grade II, and 18/28 (64%) grade III tumors. βΙΙI-tubulin overexpression was more common in grade II-III tumors compared with grade I tumors (51% vs. 0%, p=0.01, 2-sided Fisher's exact test). When evaluated by molecular subtypes, βΙΙΙ-tubulin overexpression occurred in 4/17 (24%) luminal A, 2/7 (29%) luminal B, 5/6 (83%) Her2 and 11/20 (55%) basal-like tumors. βΙΙΙ-tubulin overexpression was less common in luminal A and B subtypes compared with Her2 and basal-like subtypes (25% vs. 62%, p=0.01, 2-sided Fisher's exact test).
Conclusions: Aberrant overexpression of βΙΙΙ-tubulin is associated with high grade tumors and Her2 and basal-like breast cancer subtypes. Further evaluation is needed in order to determine whether βΙΙΙ-tubulin overexpression is independently associated with resistance to chemotherapy, including antitubulins and other agents.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 6, Wednesday Afternoon