Coexpression of MYC and BCL-2 predicts prognosis in primary gastrointestinal diffuse large B-cell lymphoma.
OBJECTIVE
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.


CONCLUSIONS
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.
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.
Bing
B
Xia
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
L
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.
Shan-Qi
SQ
Guo
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.
Xiao-Wu
XW
Li
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.
Fu-Lian
FL
Qu
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.
Hai-Feng
HF
Zhao
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.
Lian-Yu
LY
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.
Bao-Cun
BC
Sun
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.
James
J
You
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.
Yi-Zhuo
YZ
Zhang
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China; D018572:Disease-Free Survival; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006785:Hospitals, University; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis* / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
C000595707:BCL2 protein, human; D014408:Biomarkers, Tumor; C489427:MYC protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger
BCL-2; MYC; Primary gastrointestinal diffuse large B-cell lymphoma; Prognosis; Survival