The Expression of Tocopherol Associated Protein (TAP) Is Associated with Recurrence and Survival Rates in Node Positive Breast Cancer Patients.
Xi Wang, Brian Ring, David Hicks, Shuyuan Yeh, Kurstin Woolf, Rod Beck. University of Rochester Medical Center, NY; Clarient Institute, Huntsville
Background: TAP is a vitamin E binding protein. It has been shown to exert a tumor suppressor-like function in a vitamin E dependent or independent fashion. Previous studies have demonstrated that while TAP is expressed in normal/benign breast luminal cells, it is down regulated in 57% of invasive breast carcinomas.
Design: Immunohistochemical stain for TAP was performed on (1) a tissue micro-array with a breast cancer cohort comprising 288 patient samples from the Comprehensive Cancer Institute of Huntsville (CCIH), with a median follow up time 1892 days; (2) 71 breast carcinomas identified in University of Rochester for which the Oncotype DX recurrene scores (RS) have been determined.
Results: In the CCIH breast cohort, TAP is positive in 90 and negative in 198 of total 288 breast carcinomas. In 271 patients with follow up data, patients with TAP positive tumors had a lower recurrence rate (N=271, p=0.023) and better survival rate (N=265, p=0.002). This association is stronger in node positive patients (recurrence: N=118 and p=0.0004; survival: N=114 and p=0.0002), while not significant in node negative patients (recurrence: N=151 and p=0.31; survival: N=151 and p=0.87). In node positive patients, the association between TAP positivity and better prognosis is significant independent of chemo status. In patients with ER+/PR+/Her2- tumors (N=51), TAP positivity is associated with better survival (p=0.007), but the association with lower recurrence did not reach significance (p=0.078). In patients with Her2+ tumors, TAP positivity is associated with lower recurrence (N=61, p=0.001) and better survival (N=60, p=0.009) in node positive patients, but not in node negative patients. No association of TAP with better prognosis was identified in patients with triple negative tumors. In the 71 tumors with RS, TAP is positive in 47 cases (66.2%), with 29 of 43 (67.4%) in low risk group, 16 of 24 (66.7%) in intermediate risk group, and 2 of 4 (50%) in high risk group.
Conclusions: TAP as a tumor suppressor-like factor is down regulated in breast carcinomas. This down regulation is associated with higher recurrence rate and lower survival rate, especially in node positive patients, regardless of chemotherapy status. TAP expression is not associated with the RS of the Oncotype DX 21 genes assay which is targeting the node negative patients. This is consistent with the CCIH cohort results, in which TAP expression is not associated with the prognosis in node negative patients.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 9, Wednesday Afternoon