Down-Regulation of {beta}1C Integrin in Breast Carcinomas Correlates with High Proliferative Fraction, High Histological Grade, and Larger Size

摘要

ß_1C integrin is an unspliced form of the integrin ß₁ subfamily, which has been shown to inhibit cell proliferation in vitro. Using an affinity-purified rabbit antibody, we have investigated 283 previously untreated breast carcinomas, with the aim of ascertaining the actual prevalence of ß_1C expression in these tumors and of defining its pathological correlates. Immunoblotting and reverse transcriptase-polymerase chain reaction experiments have also been performed in selected cases, to confirm the immunocytochemical findings. Overall, ß_1C immunoreactivity was down-regulated (ie, expressed in < 50% of the neoplastic cells) in 114 cases (40.3%). Down-regulation of ß_1C expression in breast carcinomas correlated significantly with the tumor grade, the proliferative fraction (as evaluated by Ki-67 immunostaining with the MIB-1 monoclonal antibody), the estrogen and progesterone receptor status, and the tumor size (pT classification) and marginally with the node status. In a multivariate analysis with all available measures fitted simultaneously, tumor grade (P = 0.004), Ki-67 immunolabeling (P = 0.01), and pT categories (P = 0.04) were significantly associated with ß_1C immunoreactivity. Although the short follow-up time (2–3 years) of the current series of patients does not allow the performance of survival analyses, the correlation of ß_1C expression with tumor size, grade, and proliferative fraction and its alleged role as an upstream regulator of p27kip1 make this integrin variant a likely novel prognostic parameter for invasive carcinomas of the breast.