Expression of Sox9 Is Significantly Associated with Basal-Like Phenotype in Invasive Mammary Carcinoma
S Lu, A Mercurio, M Prasad, A Khan. University of Massachusetts Medical School, Worcester, MA; UMassMemorial Medical Center, Worcester, MA
Background: Basal-like tumors are a subset of breast cancer defined by molecular profiling that retain expression of basal keratins but lack estrogen and progesterone receptors and express low amounts of HER2. They have been found to be associated with a worse overall and disease-free survival. A handful of biomarkers for basal-like tumor have been identified, but the underlying factors that drive this phenotype are largely unknown. Sex-determining region Y-box 9 (Sox9) is an embryonic transcription factor that plays pivotal role in chondrogenesis and organogenesis of testis, pancreas, gastrointestinal tract, prostate gland, and skin. In this retrospective study we examined Sox9 expression in invasive ductal carcinoma (IDC) of the breast and correlated its expression with established prognostic factors.
Design: The study group comprised of 67 cases of poorly differentiated IDC retrieved from the files over a 5-year period (1997-2001). Tumor characteristics including size, lympho-vascular invasion, necrosis, lymph node metastasis, ER, PR, and HER-2 status were obtained from pathology reports. Immunohistochemistry was performed on formalin fixed, paraffin embedded tissue using a rabbit polyclonal antibody against Sox9. Data for cytokeratin 5/6 and beta4-integrin was available on these cases from our earlier studies. Nuclear staining of greater than 10% of tumor cells was considered positive for Sox9 expression. Statistical analysis was performed by Chi-square test using JMP 6.0 (SAS Institute).
Results: Of the total 67 poorly differentiated IDC cases, Sox9 expression was seen in 35 (52%). Of the 67 cases, 17 were ER/PR and HER-2 negative (triple negative) with basal-like phenotype, 14 (82%) of these were Sox9 positive. Within this group of high grade IDC there was significantly increased Sox9 expression in basal-like breast cancer compared to the non-basal tumors (p = 0.0029). Moreover, Sox9 expression was also positively associated with two basal-like breast cancer markers, cytokeratin 5/6 (P<0.0001) and beta4-integrin (P<0.0001).
Conclusions: Sox9 is a novel biomarker for triple negative (basal-like) invasive mammary carcinoma; its expression is associated with a more aggressive phenotype and correlates with other basal-like markers. Further examining the roles of Sox9 in breast cancer and identifying its mammary gland specific targets may be useful to understanding the transcriptional regulation of basal-like phenotype.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 41, Tuesday Afternoon