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p66 Shc Tumor Levels Show a Strong Prognostic Correlation with Disease Outcome in Stage IIA Colon Cancer

Authors' Affiliations: Departments of ¹ Cancer Biology, ² Medicine, and ³ Pathology, and ⁴ Gastrointestinal Cancer Program, University of Massachusetts Memorial Cancer Center and University of Massachusetts Medical School; ⁵ Catalyst Oncology, Inc., Worcester, Massachusetts; ⁶ Department of Pathology, Rhode Island Hospital; ⁷ Departments of Medicine, Pathology, and Laboratory Medicine, Brown University; and ⁸ Department of Research, Roger Williams Medical Center, Providence, Rhode Island

Requests for reprints: Steven R. Grossman, Department of Cancer Biology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605. Phone: 508-856-6423; E-mail: Steven.Grossman{at}umassmed.edu.

Purpose: Most stage IIA colon cancer patients receive no adjuvant therapy despite an estimated 15% risk of disease-related death within 5 years of resection. Prognostication of disease outcome would benefit the clinician by categorizing patients with stage IIA disease by risk. The abundance of the signal transduction proteins p66 Shc and tyrosine-phosphorylated (PY)-Shc in tumor cells is a prognostic indicator of disease outcome in breast cancer, suggesting that Shc analysis may provide prognostic information in stage IIA colon cancer.

Experimental Design: Immunohistochemical staining of p66 Shc and PY-Shc was examined in resection specimens from 240 chemotherapy-naïve patients with stage IIA (T₃N₀M₀) colon cancer from two independent (130 and 110 cases, respectively) retrospective cohorts. Staining was scored on a 0 to 5 scale and correlated with relapse-free survival and disease-specific survival in a multivariate analysis to obtain hazard ratios (HR) for both outcomes.

Results: In a pooled analysis of both cohorts, p66 Shc score was a significant prognostic indicator of relapse-free survival (full-range HR, 13.0; P = 0.012) and disease-specific survival (full-range HR, 36.6; P = 0.004) when analyzed as a continuous variable in a multivariate Cox proportional hazards model stratified by study site and adjusted for age, sex, grade, and lymphovascular involvement. PY-Shc in this multivariate Cox model, however, did not achieve statistical significance for either outcome.

Conclusions: Measuring p66 Shc tumor levels provides a unique and simple tool for stratifying stage IIA colon cancer patients by risk of recurrence and disease-specific death and may assist in determining treatment strategies for these patients.