Src Expression in Infiltrating Breast Carcinoma with Hormone Receptor Positive: Prognostic Significance.
Tania A Muci, Laura Sanchez-Tejada, Cristina Alenda, Maria Niveiro, Javier Segui, Gloria Peiro, Francisco I Aranda. Hospital General Universitario, Alicante, Spain
Background: The family SRC are nonreceptor tyrosine kinases and one of the best-studied targerts for cancer therapy. Elevated Src protein has been shown in human cancer, including infiltrating breast carcinoma (IBC). The aims of this study was to investigate the expression and the prognostic significance of Src in a series of breast carcinoma with hormonal receptors (HR) positive and Her-2 negative.
Design: A total of 186 cases of IBC with HR positive/Her-2 negative, with lymphadenectomy and without neoadjuvant treatment were retrieved from the Surgical Pathology files. Median clinical follow-up was 54 months (range 11 to 247). Age ranged from 24 to 88 yrs-old (median 61, SD 13)). Histologic grade (HG) was assessed according to Nottingham criteria. Immunohistochemical (IHC) staining was performed in whole sections for ER (cut-of 10%), PgR (cut-off 10%), Ki67 (cut-off 15%), p53 (cut-off 20%) and Her-2 (2+ and <30% 3+ confirmed by FISH). Src (Src phospho Y418 antibody ab47411, Abcam) staining was performed on tissue microarrays, and nuclear (N-Src) and citoplasmatic (C-Src) were independently scored (cut-off 5%). For PIK3CA mutation study, DNA was extracted from formalin-fixed, paraffin-embedded tissues using standard methods. Analysis was performed by allelic discrimination based on real-time chemistry TaqMan MGB probes in ABI Prism 7500 Sequence Detection System (Applied Biosystems). Significant associations were identified using Chi-square and Fisher's exact test. Actuarial survival was calculated by the Kaplan-Meier method (log rank test). A p-value <0.05 was considered significant.
Results: Increased N-Src expression was observed in 21% of tumors, C-Src in 30%, high Ki67 in 31% and p53 in 3%. PIK3CA mutations were detected in 24.6% tumors. Tumors with N-Src overexpression showed PIK3CA mutation (p=0.011) and a trend towards low HG (p=0.17). In contrast, C-Src was associated only with lymph node negative status (p=0.013). Patients whose tumors showed N-Src overexpression had longer survival (OS, p=0.038) but no differences were found for c-Src expression levels (p=ns)
Conclusions: Our findings suggest that N-src overexpression in IBC with HR positive is a favourable prognostic factor.
Supported by grant PC04 FIHGUA
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 24, Wednesday Afternoon