Prognostic Value of Multiple Triple-Negative Markers in Breast Cancer
S Lu, O Walter, P Vohra, D Kandil, LJ Wang, AM Mercurio, A Khan. Warren Alpert Medical School at Brown Univeristy, Providence, RI; University of Massachusetss Medical School, Worcester, MA; University of Massachusetts Medical School, Worcester, RI
Background: Triple-negative (TN) tumors are a subset of breast cancer (BC) that lack estrogen and progesterone receptors and express low amounts of HER2. They have been found to be associated with a worse prognosis. We have previously reported four biomarkers including integrin β4, Sox9 (SRY box-9), IMP3 (IGF-II mRNA binding protein-3), and a cytoskeleton protein fascin that are significantly associated with TN BC and expression of basal cytokeratin CK5/6. Furthermore, while each of them shows a tendency towards worse prognosis the difference is not statistically significant. In this retrospective study we evaluated various combinations of these four TN markers in BC to see if expression of more than one marker together is associated with worse overall prognosis.
Design: The study group comprised of 189 cases of invasive ductal BC retrieved from the files over a 10-year period. Tumor characteristics including CK5/6, ER, PR, and HER2 status were obtained from pathology reports. IHC was performed on paraffin-embedded tissue using a rabbit PAb against Sox9, mouse MAbs against IMP3 and fascin, and a rat MAb against integrin β4. Overall survival data were available in 138 cases, of these 23% were TN. Statistical analysis was performed using JMP 8.0 (SAS Institute).
Results: All four markers are associated with TN status and a positive CK5/6 expression with statistical significance. Combination of these markers provides better predictions than any marker used alone. A total of 10 patients with quadruple positive BC had significant worse overall survival than the patients with BC not expressing at least one of these markers (P=0.0033, Kaplan-Meier log-rank test), so did 14 patients with Sox9, β4 and fascin triple positive BC (P=0.0052), and so did 17 patients with β4 and fascin double positive BC (P=0.0021). The proportional hazard analysis showed hazard ratios of 2.98 for double positivity of β4 and fascin (P=0.03).
Conclusions: Of the four markers we evaluated, combination of integrin β4 and fascin provides the best prediction for worse prognosis and is associated with the highest hazard ratio. Given their close locations within the cell, integrin [beta4] and fascin could work synergistically in the same molecular machinery or in the same pathway. TN BC is a heterogenous group and individual tumor could undergo different progression pathway.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 25, Monday Morning