MYC and BCL2 overexpression is associated with a higher class of Memorial Sloan-Kettering Cancer Center prognostic model and poor clinical outcome in primary diffuse large B-cell lymphoma of the central nervous system.
Primary diffuse large B-cell lymphoma of the central nervous system (PCNS-DLBCL) is a distinct clinicopathological entity with a poor prognosis. Concurrent MYC and BCL2 overexpression predicts inferior prognosis in systemic DLBCLs. However, the prognostic significance of MYC and BCL2 in PCNS-DLBCL remains elusive.



Immunohistochemistry (IHC) of MYC, BCL2 and BCL6 was performed on tumor samples from 114 patients with PCNS-DLBCL. IHC score was assigned based on the proportion of immunostained cells.



MYC, BCL2, and BCL6 IHC scores were 18.16 ± 19.58, 58.86 ± 35.07, and 39.39 ± 37.66 % (mean ± SD), respectively. Twenty-one cases (18.1 %) were designated as MYC-positive with a cutoff score of 40. BCL2 positivity was found in 87 cases (75.0 %) using a cutoff score of 30. MSKCC (Memorial Sloan-Kettering Cancer Center prognostic model) class 2 and 3 had higher rates of MYC and/or BCL2 positivity (MYC, P = 0.012; BCL2, P = 0.008; dual-positive, P = 0.022). Poor KPS (Karnofsky Performance Status score <70), multifocal disease, Nottingham-Barcelona score ≥2, and MSKCC class 2 and 3 were related to shorter progression-free survival (PFS) (P = 0.001, 0.037, 0.001, and 0.008, respectively). Patients with older age (>60 years) showed poorer overall survival (OS) (P = 0.020). MYC positivity was associated with poor PFS (P = 0.027), while patients with BCL2 positivity exhibited a shorter OS (P = 0.010). Concomitant MYC and BCL2 positivity was related to poor PFS (P = 0.041), while the lack of both MYC and BCL2 expression was related to prolonged OS (P = 0.014). MYC and BCL2 expression had no independent prognostic implication by multivariate analysis in overall patients with PCNS-DLBCL. However, among patients treated with combined high-dose methotrexate, vincristine and procarbazine and radiotherapy, dual MYC and BCL2 overexpression (a cutoff score of 60) was an independent poor prognostic indicator (P = 0.010).



Evaluation of MYC and BCL2 expression may be helpful for the determination of PCNS-DLBCL prognosis.
Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
Sehui
S
Kim
The Tumor Immunity Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea.|Tumor Microenvironment Global Core Research Center, Seoul National University, Seoul, Republic of Korea.|Department of Pathology, Asan Medical Center, Seoul, Republic of Korea.
Soo Jeong
SJ
Nam
Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
Dohee
D
Kwon
Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
Hannah
H
Kim
Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Eunyoung
E
Lee
Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Tae Min
TM
Kim
Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Dae Seog
DS
Heo
Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
Sung Hye
SH
Park
Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.|The Tumor Immunity Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea.|Tumor Microenvironment Global Core Research Center, Seoul National University, Seoul, Republic of Korea.
Chul Woo
CW
Kim
Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. junarplus@chol.com.|The Tumor Immunity Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea. junarplus@chol.com.|Tumor Microenvironment Global Core Research Center, Seoul National University, Seoul, Republic of Korea. junarplus@chol.com.
Yoon Kyung
0000-0001-8466-9681
YK
Jeon
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016543:Central Nervous System Neoplasms / Q000378:metabolism / Q000473:pathology*; D002648:Child; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D016019:Survival Analysis; D015854:Up-Regulation; D055815:Young Adult
C000595707:BCL2 protein, human; C489427:MYC protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc
BCL2; Diffuse large B-cell lymphoma; MYC; Primary central nervous system lymphoma; Prognosis