Title

Tissue Microarray Molecular Profiling of Early, Node-Negative Adenocarcinoma of the Rectum: A Comprehensive Analysis

Publication Type

Journal Article

Publication Date

2002

Abstract

Purpose: Early-stage adenocarcinoma of the rectum treated with curative intent has a favorable overall prognosis; however, 20%-30% of the patients recur, and the majority ultimately die of disease. Recurrence and tumor-related mortality may be attributable to molecular abnormalities in primary tumors accounting for their more aggressive biological behavior. This study evaluates such molecular phenotypes with regard to cell cycle regulation and proliferation and determines their significance for patient outcome. Experimental Design: One hundred patients with primary T2-3, N0 adenocarcinoma of the rectum uniformly treated by surgery alone were studied. Core biopsies of pathological specimens were assembled on tissue microarrays, and expression of p53, mdm-2, p21, Bcl-2, p27, cyclin D1, and Ki-67 was analyzed by immunohistochemistry. Molecular profiles were correlated with disease-free (DFS) and disease-specific survival (DSS). Results: Despite previously described prognostic relevance of some of the investigated molecules in analyses where different stages of colorectal cancer were included, none of the cell cycle-regulatory or proliferation-related markers was associated with recurrence or survival. However, patients with tumors demonstrating down-regulation of p27, a cyclin-dependent kinase inhibitor and tumor suppressor gene associated with development of metastases, showed a trend toward reduced DFS and DSS (P = 0.06 and P = 0.07, respectively). Conclusions: In this homogeneous group of patients with early-stage, node-negative adenocarcinoma of the rectum uniformly treated by surgery alone, the investigated cell cycle-regulatory and proliferation-associated proteins appear to have no prognostic significance. However, down-regulation of p27 appears to be associated with a trend toward reduced DFS and DSS, which suggests further investigation of other p27-related pathways potentially relevant for metastatic disease.

Discipline

Econometrics | Medicine and Health Sciences

Research Areas

Econometrics

Publication

Clinical Cancer Research

Volume

8

Issue

12

First Page

3841

Last Page

3849

ISSN

1078-0432

Publisher

Association for Cancer Research

Additional URL

http://clincancerres.aacrjournals.org/cgi/content/abstract/8/12/3841

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