Tissue microarray molecular profiling of early, node-negative adenocarcinoma of the rectum: A comprehensive analysis Journal Article


Authors: Hoos, A.; Nissan, A.; Stojadinovic, A.; Shia, J.; Hedvat, C. V.; Leung, D. H. Y.; Paty, P. B.; Klimstra, D.; Cordon-Cardo, C.; Wong, W. D.
Article Title: Tissue microarray molecular profiling of early, node-negative adenocarcinoma of the rectum: A comprehensive analysis
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.
Keywords: immunohistochemistry; adult; cancer survival; controlled study; human tissue; protein expression; aged; aged, 80 and over; disease-free survival; middle aged; protein array analysis; major clinical study; proto-oncogene proteins; disease course; histopathology; cancer recurrence; disease marker; cancer staging; adenocarcinoma; ki 67 antigen; cell proliferation; ki-67 antigen; phenotype; cell cycle proteins; cell cycle; protein bcl 2; metastasis; neoplasm proteins; tumor markers, biological; analytic method; tumor biopsy; protein p53; tumor marker; nuclear proteins; immunoenzyme techniques; tumor suppressor gene; correlation analysis; regulatory mechanism; protein p27; cyclin-dependent kinase inhibitor p27; tumor suppressor proteins; tumor suppressor protein p53; down regulation; cyclin-dependent kinase inhibitor p21; cyclin d1; rectum carcinoma; cyclins; rectal neoplasms; protein p21; protein determination; proto-oncogene proteins c-bcl-2; tissue; protein mdm2; proto-oncogene proteins c-mdm2; humans; prognosis; human; male; female; priority journal; article
Journal Title: Clinical Cancer Research
Volume: 8
Issue: 12
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2002-12-01
Start Page: 3841
End Page: 3849
Language: English
PUBMED: 12473598
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 14 November 2014 -- Source: Scopus
Citation Impact
MSK Authors
  1. Philip B Paty
    468 Paty
  2. Cyrus Hedvat
    126 Hedvat
  3. Denis Heng Yan Leung
    114 Leung
  4. Axel Hoos
    28 Hoos
  5. Aviram Nissan
    20 Nissan
  6. David S Klimstra
    976 Klimstra
  7. Jinru Shia
    667 Shia
  8. Douglas W Wong
    178 Wong