This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Krajewska, M. Articles by Reed, J. C. Search for Related Content PubMed PubMed Citation Articles by Krajewska, M. Articles by Reed, J. C.

Analysis of Apoptosis Protein Expression in Early-Stage Colorectal Cancer Suggests Opportunities for New Prognostic Biomarkers

Authors' Affiliations: ¹ The Burnham Institute, ² Department of Family Preventive Medicine, University of California-San Diego, La Jolla, California; ³ Pathology and ⁴ Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea; and ⁵ Department of Pathology, College of Medicine, Pochon CHA University, Kyonggi-do, Korea

Requests for reprints: John C. Reed, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037. Phone: 858-646-3140; Fax: 858-646-3194; E-mail: reedoffice{at}burnham.org.

Purpose: Although most stage II colon cancers are potentially curable by surgery alone, 20% of patients relapse, suggesting a need for establishing prognostic markers that can identify patients who may benefit from adjuvant chemotherapy. We tested the hypothesis that differences in expression of apoptosis-regulating proteins account for differences in clinical outcome among patients with early-stage colorectal cancer.

Experimental Design: Tissue microarray technology was employed to assay the expression of apoptosis-regulating proteins by immunohistochemistry in 106 archival stage II colorectal cancers, making correlations with disease-specific survival. The influence of microsatellite instability (MSI), tumor location (left versus right side), patient age, and gender was also examined.

Results: Elevated expression of several apoptosis regulators significantly correlated with either shorter (cIAP2; TUCAN) or longer (Apaf1; Bcl-2) overall survival in univariate and multivariate analyses. These biomarkers retained prognostic significance when adjusting for MSI, tumor location, patient age, and gender. Moreover, certain combinations of apoptosis biomarkers were highly predictive of death risk from cancer. For example, 97% of patients with favorable tumor phenotype of cIAP2^low plus TUCAN^low were alive at 5 years compared with 60% of other patients (P = 0.00003). In contrast, only 37% of patients with adverse biomarkers (Apaf1^low plus TUCAN^high) survived compared with 83% of others at 5 years after diagnosis (P< 0.0001).

Conclusions: Immunohistochemical assays directed at detection of certain combinations of apoptosis proteins may provide prognostic information for patients with early-stage colorectal cancer, and therefore could help to identify patients who might benefit from adjuvant chemotherapy or who should be spared it.

This article has been cited by other articles:

				M. Krajewska, S. Kitada, J. N. Winter, D. Variakojis, A. Lichtenstein, D. Zhai, M. Cuddy, X. Huang, F. Luciano, C. H. Baker, et al. Bcl-B Expression in Human Epithelial and Nonepithelial Malignancies Clin. Cancer Res., May 15, 2008; 14(10): 3011 - 3021. [Abstract] [Full Text] [PDF]

				K. W. Sherrill and R. E. Lloyd Translation of cIAP2 mRNA Is Mediated Exclusively by a Stress-Modulated Ribosome Shunt Mol. Cell. Biol., March 15, 2008; 28(6): 2011 - 2022. [Abstract] [Full Text] [PDF]

				C. Shanmugam, V. R. Katkoori, N. C. Jhala, W. E. Grizzle, G. P. Siegal, and U. Manne p53 Nuclear Accumulation and Bcl-2 Expression in Contiguous Adenomatous Components of Colorectal Adenocarcinomas Predict Aggressive Tumor Behavior J. Histochem. Cytochem., March 1, 2008; 56(3): 305 - 312. [Abstract] [Full Text] [PDF]

				D. B. Seligson, F. Hongo, S. Huerta-Yepez, Y. Mizutani, T. Miki, H. Yu, S. Horvath, D. Chia, L. Goodglick, and B. Bonavida Expression of X-Linked Inhibitor of Apoptosis Protein Is a Strong Predictor of Human Prostate Cancer Recurrence Clin. Cancer Res., October 15, 2007; 13(20): 6056 - 6063. [Abstract] [Full Text] [PDF]

				S. R. Grossman, S. Lyle, M. B. Resnick, E. Sabo, R. T. Lis, E. Rosinha, Q. Liu, C.-C. Hsieh, G. Bhat, A. R. Frackelton Jr., et al. p66 Shc Tumor Levels Show a Strong Prognostic Correlation with Disease Outcome in Stage IIA Colon Cancer Clin. Cancer Res., October 1, 2007; 13(19): 5798 - 5804. [Abstract] [Full Text] [PDF]