Expression of apoptosis regulating proteins identifies stage II and III colon cancer patients with high risk of recurrence

• Published in: Journal of surgical oncology Vol. 109; no. 3; pp. 255 - 265
• Main Authors: Belt, Eric J.Th, Stockmann, Hein B.A.C., Delis-van Diemen, Pien M., Bril, Herman, Tijssen, Marianne, van Essen, Hendrik F., Heymans, Martijn W., Beliën, Jeroen A.M., Carvalho, Beatriz, Cillessen, Saskia A.G.M., Meijer, Gerrit A.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.03.2014; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; Aged, 80 and over; apoptosis; Apoptosis Regulatory Proteins - analysis; Apoptosis Regulatory Proteins - genetics; bcl-2-Associated X Protein - analysis; bcl-X Protein - analysis; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; CASP8 and FADD-Like Apoptosis Regulating Protein - analysis; colon cancer; Colonic Neoplasms - chemistry; Colonic Neoplasms - genetics; Colonic Neoplasms - pathology; Disease-Free Survival; DNA, Neoplasm - metabolism; Fas Ligand Protein - analysis; fas Receptor - analysis; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Male; Microsatellite Instability; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Prognosis; proteins; Proto-Oncogene Proteins c-bcl-2 - analysis; Recurrence; Risk Assessment; Risk Factors; Tissue Array Analysis; X-Linked Inhibitor of Apoptosis Protein - analysis; recurrence; apoptosis; colon cancer; proteins
• ISSN: 0022-4790; 1096-9098
• DOI: 10.1002/jso.23495

Background and Objectives Deregulation of apoptosis related genes may be associated with poor outcome in cancer. Aim of the present study was to investigate the prognostic role of expression levels of apoptosis related proteins in stage II and III colon cancer. Methods From tumor samples of 386 stage II and III colon cancer patients, DNA was isolated and tissue microarrays were constructed. Expression of Bcl‐2, Bcl‐X, BAX, XIAP, Fas, FasL and c‐FLIP was evaluated and PCR‐based microsatellite instability analysis was performed. Results High FasL expressing tumors were associated with high disease recurrence rates in stage II colon cancer patients overall, as was low Bcl‐X expression in microsatellite stable stage II patients. In stage II patients, a multivariable model based on FasL and Bcl‐XL expression revealed a significant association with disease free survival (DFS). In stage III colon cancer patients, low Bcl‐2, low BAX and low Fas expression levels were associated with worse outcome. In these patients a multivariable model based on angioinvasion and Bcl‐2, Fas and FasL expression was significantly associated with DFS. Conclusions Stage II patients with low Bcl‐X and high FasL protein expression levels and stage III patients with low Fas, high FasL and low Bcl‐2 expression could be considered as high risk for disease recurrence. J. Surg. Oncol. 2014 109:255–265. © 2013 Wiley Periodicals, Inc.