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Prognostic Groups in Colorectal Carcinoma Patients Based on Tumor Cell Proliferation and Classification and Regression Tree (CART) Survival Analysis

¹ First Department of Surgery, Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi Dori, Niigata City 951-8510, Japan
² Department of Otolaryngology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Japan
³ Third Department of Anatomy, Division of Microscopic Anatomy and Bioimaging, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Japan

Correspondence: Address correspondence and reprint requests to: Vladimir A. Valera, MD, PhD; E-mail: vvalerar{at}med.niigata-u.ac.jp

Background: In this study, an alternative analytical method was used to model colorectal cancer (CRC) patients’ long-term survival by assessing the prognostic value of the Ki-67 protein as a marker of tumor cell proliferation, and to illustrate the interaction between standard clinicopathologic variables and the proliferation marker in relation to their impact on survival.

Methods: A cohort of 106 surgically treated CRC patients was used for analysis. The expression of the cell-cycle-related Ki-67 protein in tumor samples was evaluated by immunohistochemistry. A score was assigned as the percentage of positive tumor cell staining, denoted as proliferation index (PI), and was used in a multivariate analysis using a recursive partitioning algorithm referred to as classification and regression tree (CART) to characterize the long-term survival after surgery.

Results: Of the covariates selected for their prognostic value, PI contributed most to the classification of survival status of patients. However, CART analysis selected the presence of distant metastasis as the best first split-up factor for predicting 5-year survival. CART then selected the following covariates for building up subgroups at risk for death: (1) PI; (2) pathological lymph node metastasis; (3) tumor size. Seven terminal subgroups were formed, with an overall misclassification rate of 16%.

Conclusions: These analyses demonstrated that a Ki-67-protein-based tumor proliferation index appeared as an independent prognostic variable that was consistently applied by the CART algorithm to classify patients into groups with similar clinical features and survival.

Key Words: Colorectal carcinomas • Proliferation index • Ki-67 • CART analysis • Prognosis

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