PMID- 29325248 OWN - NLM STAT- MEDLINE DCOM- 20180202 LR - 20211204 IS - 0529-5807 (Print) IS - 0529-5807 (Linking) VI - 47 IP - 1 DP - 2018 Jan 8 TI - [Survival of patients with primary central nervous system diffuse large B-cell lymphoma: impact of gene aberrations and protein overexpression of bcl-2 and C-MYC, and selection of chemotherapy regimens]. PG - 32-38 LID - 10.3760/cma.j.issn.0529-5807.2018.01.007 [doi] AB - Objective: To investigate the impact of clinicopathological features, gene rearrangements and protein expression of bcl-6, bcl-2, C-MYC and chemotherapy regime on the prognosis of patients with primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL). Methods: Thirty-three cases of PCNS-DLBCL diagnosed from January 2006 to December 2016 at Zhejiang Cancer Hospital were collected. The expression of CD10, bcl-6, bcl-2, MUM1 and MYC were detected by immunohistochemical staining (IHC). The presence of EB virus was detected by in situ hybridization(EBER). Copy number variation (ICN) and translocation status of bcl-6, bcl-2 and C-MYC genes were detected by fluorescence in situ hybridization (FISH). The relationship between the above indexes and the prognosis was analyzed by univariate, bivariate survival analysis and multiple Cox hazard regression analysis. Results: The study included 33 patients of PCNS-DLBCL, without evidence of primary or secondary immunodeficient disease. Male to female ratio was 1.36ratio1.00, and the average age was 56 years. Twenty cases had single lesion while 13 had multiple lesions. Deep brain involvement was seen in 12 cases. All patients underwent partial or total tumor resection. Five patients received whole brain post-surgery radiotherapy, nine patients received high-dose methotrexate (HD-MTX) based chemotherapy, and 12 patients received whole-brain radiotherapy combined with HD-MTX based chemotherapy. Severn patients received no further treatment and rituximab was used in 8 patients. According to the Hans model, 27 cases were classified as non-GCB subtypes (81.8%). Bcl-2 was positive in 25 cases (75.8%, 25/33) and highly expressed in 8 (24.2%). MYC was positive in 12 cases (36.4%) and double expression of bcl-2 and MYC was seen in 6 cases. EBER positive rate was 10.0%(3/30), all of which had multiple lesions. Two bcl-6 gene translocations and 3 amplifications were found in 28 patients. Two translocations, 3 ICN or with both bcl-2 gene translocation and ICN were found in 30 patients. Four ICNs of C-MYC gene were found in 28 patients. Elevated protein in cerebrospinal fluid (CSF) was found in 13 patients. LDH increased in 10 cases. Follow-up period was 2-90 months with the average survival time of (23.0+/-3.7) months and two-year survival rate of 39.0%. Univariate survival analysis showed that overexpression of bcl-2 protein (>/=70%) and MYC protein (>/=40%), bcl-2 gene abnormality (including copy number increase and translocation), C-MYC gene copy number increased were adverse factors for survival. C-MYC/ bcl-2 gene double hit was seen in 2 cases. Bivariate survival analysis found that of bcl-2/MYC protein double expression and bcl-2 and C-MYC genes double aberration were significantly associated with adverse outcomes. Cox multivariate risk regression analysis found that gender, cerebrospinal fluid protein increasing, and ICN of C-MYC gene were independent poor prognostic factors. DH-MTX based comprehensive chemotherapy was associated with better prognosis. Conclusions: Double hit at genomic level (copy number variations and gene rearrangements) and double protein expression of bcl-2 and C-MYC in PCNS-DLBCL are significantly associated with an adverse outcome. DH-MTX based comprehensive treatment may prolong the patient survival. FAU - Yin, W J AU - Yin WJ AD - Department of Pathology, Zhejiang Cancer Hospital, Hangzhou 310022, China. FAU - Zhu, X AU - Zhu X FAU - Yang, H Y AU - Yang HY FAU - Sun, W Y AU - Sun WY FAU - Wu, M J AU - Wu MJ LA - chi PT - Journal Article PL - China TA - Zhonghua Bing Li Xue Za Zhi JT - Zhonghua bing li xue za zhi = Chinese journal of pathology JID - 0005331 RN - 0 (Antimetabolites, Antineoplastic) RN - 0 (BCL2 protein, human) RN - 0 (Interferon Regulatory Factors) RN - 0 (MAS1 protein, human) RN - 0 (Proto-Oncogene Mas) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Proto-Oncogene Proteins c-bcl-6) RN - 0 (Proto-Oncogene Proteins c-myc) RN - 0 (interferon regulatory factor-4) RN - EC 3.4.24.11 (Neprilysin) RN - YL5FZ2Y5U1 (Methotrexate) SB - IM MH - Antimetabolites, Antineoplastic/therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Brain Neoplasms/metabolism/mortality/pathology/therapy MH - Central Nervous System Neoplasms/genetics/metabolism/*mortality/therapy MH - DNA Copy Number Variations MH - Female MH - Gene Dosage MH - *Gene Rearrangement MH - Genes, bcl-2 MH - Genes, myc MH - Herpesvirus 4, Human/isolation & purification MH - Humans MH - In Situ Hybridization, Fluorescence MH - Interferon Regulatory Factors/metabolism MH - Lymphoma, Large B-Cell, Diffuse/genetics/metabolism/*mortality/therapy MH - Male MH - Methotrexate/therapeutic use MH - Middle Aged MH - Neprilysin/metabolism MH - Prognosis MH - Proto-Oncogene Mas MH - Proto-Oncogene Proteins c-bcl-2/*metabolism MH - Proto-Oncogene Proteins c-bcl-6/genetics/metabolism MH - Proto-Oncogene Proteins c-myc/*metabolism MH - Survival Analysis MH - Survival Rate MH - Translocation, Genetic OTO - NOTNLM OT - Central nervous system neoplasms OT - Genes, myc OT - Lymphoma, large B-cell, diffuse OT - Prognosis OT - Proto-oncogene proteins c-myc OT - bcl-2 protein EDAT- 2018/01/13 06:00 MHDA- 2018/02/03 06:00 CRDT- 2018/01/12 06:00 PHST- 2018/01/12 06:00 [entrez] PHST- 2018/01/13 06:00 [pubmed] PHST- 2018/02/03 06:00 [medline] AID - 10.3760/cma.j.issn.0529-5807.2018.01.007 [doi] PST - ppublish SO - Zhonghua Bing Li Xue Za Zhi. 2018 Jan 8;47(1):32-38. doi: 10.3760/cma.j.issn.0529-5807.2018.01.007.