Recurrence and survival predictive value of phenotypic expression of Bcl-2 varies with tumor stage of colorectal adenocarcinoma

Issue title: The Needs and Development of Physical Standards for Medical Diagnostics and Research

Guest editors: Peter E. Barker

Article type: Research Article

Authors: Chatla, Chakrapani^a | Jhala, Nirag C.^a | Katkoori, Venkat R.^a | Alexander, Dominik^b | Meleth, Sreelatha^c | Grizzle, William E.^a | Manne, Upender^{a; *}

Affiliations: [a] Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA | [b] Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA | [c] Department of Biostatistics and Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA | NIST Division of Biochemical Sciences, Chemical Sciences and Technology Laboratory, National Institute of Standards and Technology, Gaithersburg, MD, USA

Correspondence: [*] Corresponding author: Upender Manne, MS., Ph.D., Associate Professor, Department of Pathology, University of Alabama at Birmingham, 523-Kracke Building, 1922, 7th Avenue South, Birmingham, AL, 35294-7331, USA. Tel.: +1 205 934 4276; Fax: +1 205 934 4418; E-mail: [email protected].

Abstract: Although decreased or lack of expression of Bcl-2 has been correlated with advanced tumor stage and shortened patient survival in colorectal cancer (CRC), its value in predicting the recurrence has not been well explored. Therefore, we assessed the usefulness of phenotypic expression of Bcl-2 in non-Hispanic Caucasian patients with CRCs in identifying risk of recurrence. Archival tissues of 92 Stage II and 66 Stage III primary CRCs were evaluated for immunohistochemical expression of Bcl-2. None of these patients received either pre- or post-surgical adjuvant therapies. Kaplan-Meier and Cox proportional hazards methods were used to estimate the rates of recurrence and survival according to Bcl-2 expression. Decreased expression of Bcl-2 was associated with an increased rate of recurrence in patients with Stage II CRCs (5-year log-rank test P=0.0015; Hazard Ratio (HR)=3.90, 95%C.I.:1.55–9.77) but not with Stage III CRCs (5-year log-rank test P=0.6058; HR=1.07, 95%C.I.:0.47–2.45) after adjusting for other demographic and clinicopathological features. Furthermore, decreased expression of Bcl-2 was an indicator of short survival in patients with Stage II CRCs but not with Stage III CRCs. Thus, decreased or lack of Bcl-2 expression in primary CRCs may serve as a molecular biomarker of high risk of recurrence for Caucasian patients with Stage II CRCs. These findings might be useful in identifying biologically aggressive phenotypes of Stage II CRCs, and may aid the oncologist in designing maximally appropriate therapeutic regimens.

Keywords: Colorectal adenocarcinoma, Bcl-2 expression, tumor stage, caucasians, recurrence, and prognosis

DOI: 10.3233/CBM-2005-14-507

Journal: Cancer Biomarkers, vol. 1, no. 4-5, pp. 241-250, 2005