Clinical Trials Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2015; 21(8): 2433-2442
Published online Feb 28, 2015. doi: 10.3748/wjg.v21.i8.2433
Coexpression of MYC and BCL-2 predicts prognosis in primary gastrointestinal diffuse large B-cell lymphoma
Bing Xia, Le Zhang, Shan-Qi Guo, Xiao-Wu Li, Fu-Lian Qu, Hai-Feng Zhao, Lian-Yu Zhang, Bao-Cun Sun, James You, Yi-Zhuo Zhang
Bing Xia, Le Zhang, Shan-Qi Guo, Xiao-Wu Li, Fu-Lian Qu, Hai-Feng Zhao, Yi-Zhuo Zhang, Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
Le Zhang, Ruijin Hospital and Medical School of Shanghai Jiao Tong University, Shanghai 200025, China
Lian-Yu Zhang, Bao-Cun Sun, Department of Pathology, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
James You, Department of Hematopathology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77036, United States
Author contributions: Zhang L and Xia B contributed equally to this manuscript as co-first authors; Zhang L, Xia B, Guo SQ, Li XW, Qu FL, Zhao HF performed all the in vitro experiments and contributed to manuscript preparation; Zhang LY, Sun BC provided essential reagents, clinical samples, and information and intellectual support; Zhang L, Xia B and Zhang YZ designed experiments, interpreted data and wrote the manuscript; all authors approved the final version of the manuscript.
Supported by National Natural Science Foundation of China, No. 30672208, No. 81270603 and No. 31301161; and Tianjin Natural Science Foundation of China, No. 13JCYBJC22800.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Yi-Zhuo Zhang, Professor, Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China. yizhuozhang111@163.com
Telephone: +86-22-2359337 Fax: +86-22-2359337
Received: August 19, 2014
Peer-review started: August 20, 2014
First decision: September 27, 2014
Revised: November 6, 2014
Accepted: December 22, 2014
Article in press: December 22, 2014
Published online: February 28, 2015
Processing time: 193 Days and 5.4 Hours
Abstract

AIM: To investigate whether MYC and BCL-2 coexpression has prognostic significance in primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) patients, and explore its associations with patients’ clinical parameters.

METHODS: Fresh and paraffin-embedded tumor tissue samples from 60 PGI-DLBCL patients who had undergone surgery at the Tianjin Medical University Cancer Institute and Hospital from January 2005 to May 2010 were obtained, and 30 lymphoid tissue samples from reactive lymph nodes of age- and sex-matched patients represented control samples. Staging and diagnostic procedures were conducted according to the Lugano staging system. All patients had been treated with three therapeutic modalities: surgery, chemotherapy, or radiotherapy. Expression of MYC and BCL-2 were detected at both protein and mRNA levels by immunohistochemistry and real-time RT-PCR.

RESULTS: Positive expression levels of MYC and BCL-2 proteins were detected in 35% and 45% of patients, respectively. MYC+/BCL-2+ protein was present in 30% of patients. MYC and BCL-2 protein levels were correlated with high MYC and BCL-2 mRNA expression, respectively (both P < 0.05). We found that advanced-stage disease (at IIE-IV) was associated with MYC and BCL-2 coexpression levels (P < 0.05). In addition, MYC+/BCL-2+ patients had more difficulty in achieving complete remission than others (P < 0.05). Presence of MYC protein expression only affected overall survival and progression-free survival (PFS) when BCL-2 protein was coexpressed. The adverse prognostic impact of MYC+/BCL-2+ protein on PFS remained significant (P < 0.05) even after adjusting for age, Lugano stage, international prognostic index, and BCL-2 protein expression in a multivariable model.

CONCLUSION: MYC+/BCL-2+ patients have worse chemotherapy response and poorer prognosis than patients who only express one of the two proteins, suggesting that assessment of MYC and BCL-2 expression by immunohistochemistry has clinical significance in predicting clinical outcomes of PGI-DLBCL patients.

Keywords: MYC; BCL-2; Survival; Primary gastrointestinal diffuse large B-cell lymphoma; Prognosis

Core tip: We investigated MYC and BCL-2 coexpression in primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) and explored its associations with patients’ clinical parameters. In contrast to previously published results about MYC/BCL-2 coexpression in DLBCL, this study focused on PGI-DLBCL. Although PGI-DLBCL is rare, we had a large collection of 60 PGI-DLBCL cases to test the protein and mRNA levels of MYC and BCL-2. We found that MYC+/BCL-2+ patients have worse chemotherapy response and poorer prognosis than patients who only express one of the two proteins, suggesting that assessment of MYC and BCL-2 expression has clinical significance in predicting clinical outcomes of PGI-DLBCL patients.