PMID- 25828389 OWN - NLM STAT- MEDLINE DCOM- 20151103 LR - 20151119 IS - 1532-0979 (Electronic) IS - 0147-5185 (Linking) VI - 39 IP - 9 DP - 2015 Sep TI - MYC cytogenetic status correlates with expression and has prognostic significance in patients with MYC/BCL2 protein double-positive diffuse large B-cell lymphoma. PG - 1250-8 LID - 10.1097/PAS.0000000000000433 [doi] AB - MYC/BCL2 double-hit lymphoma (DHL), defined by conventional cytogenetic or fluorescence in situ hybridization (FISH) analysis, and MYC/BCL2 double-positive lymphoma (DPL), defined by immunohistochemistry, are associated with a poor prognosis. However, DHL and DPL are not concordant, and it is unclear whether MYC and BCL2 aberrations have prognostic impact in DPL patients. In a cohort of 135 patients diagnosed with large B-cell lymphoma between 2010 and 2014 in whom MYC/8q24 and BCL2/t(14;18)(q32;q21) statuses were assessed by FISH at diagnosis, we evaluated MYC and BCL2 expression by immunohistochemistry. A total of 54 (40%) cases were positive for MYC and BCL2 supporting DPL. Among them, 19 (35%) had MYC rearrangement including 11 DHLs, 12 (22%) had multiple copies of MYC, 19 had no MYC abnormalities, and in 4 cases FISH analysis failed. BCL2 abnormalities were present in 28/54 (52%) cases (20 rearranged and 8 multiple copies). MYC rearrangement correlated with a significantly worse overall survival in DPL (P<0.05), whereas BCL2 genetic status did not correlate with survival (P>0.05). MYC and BCL2 expression by immunohistochemistry correlates with gene status by FISH; however, immunohistochemistry is neither specific nor adequately sensitive to be used as a surrogate for MYC and BCL2 gene status using any cutoff level. In conclusion, MYC rearrangement identifies a subset of patients with DPL who have a significantly worse prognosis. Although immunohistochemical assessment for MYC and BCL2 may be a helpful initial screen to identify higher-risk patients, FISH analysis for MYC remains important for further risk stratification in patients with DPL. FAU - Wang, Xuan Julia AU - Wang XJ AD - *Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN daggerDepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Medeiros, L Jeffrey AU - Medeiros LJ FAU - Lin, Pei AU - Lin P FAU - Yin, C Cameron AU - Yin CC FAU - Hu, Shimin AU - Hu S FAU - Thompson, Mary Ann AU - Thompson MA FAU - Li, Shaoying AU - Li S LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - Am J Surg Pathol JT - The American journal of surgical pathology JID - 7707904 RN - 0 (BCL2 protein, human) RN - 0 (Biomarkers, Tumor) RN - 0 (MYC protein, human) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Proto-Oncogene Proteins c-myc) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/analysis/*genetics MH - Female MH - Gene Amplification MH - Gene Rearrangement MH - Genetic Predisposition to Disease MH - Humans MH - *Immunohistochemistry MH - *In Situ Hybridization, Fluorescence MH - Kaplan-Meier Estimate MH - Lymphoma, Large B-Cell, Diffuse/chemistry/*genetics/mortality/pathology MH - Male MH - Middle Aged MH - Phenotype MH - Predictive Value of Tests MH - Prognosis MH - Proto-Oncogene Proteins c-bcl-2/analysis/*genetics MH - Proto-Oncogene Proteins c-myc/analysis/*genetics MH - Reproducibility of Results MH - Time Factors MH - Young Adult EDAT- 2015/04/02 06:00 MHDA- 2015/11/04 06:00 CRDT- 2015/04/02 06:00 PHST- 2015/04/02 06:00 [entrez] PHST- 2015/04/02 06:00 [pubmed] PHST- 2015/11/04 06:00 [medline] AID - 10.1097/PAS.0000000000000433 [doi] PST - ppublish SO - Am J Surg Pathol. 2015 Sep;39(9):1250-8. doi: 10.1097/PAS.0000000000000433.