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From the Departments of Pathology and Laboratory
Medicine*
and Epidemiology and
Biostatistics,
European Institute of Oncology,
University of Milan School of Medicine, Milan, Italy; and the
Department of Pathology,
Yale University
School of Medicine, New Haven, Connecticut
ß1C 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 ß1C 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, ß1C immunoreactivity was down-regulated (ie, expressed in < 50% of the neoplastic cells) in 114 cases (40.3%). Down-regulation of ß1C 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 ß1C 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 ß1C 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.
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