Abstract
Microsatellite instability (MSI) has been investigated as a prognostic and predictive factor for chemotherapy in colorectal cancer and has recently been demonstrated to be predictive of the PD‐1/PD‐L1 checkpoint blockade response in various solid tumors. However, MSI status in diffuse large B‐cell lymphomas (DLBCLs) has not been thoroughly explored. This study investigated MSI status in DLBCLs and analyzed the associations between MSI and clinicopathologic characteristics and clinical outcomes. Ninety‐two cases of primary DLBCLs treated with R‐CHOP/CHOP chemotherapy between 2009 and 2017 were collected. MSI detection was performed by the Promega MSI Analysis System. The protein expression of MLH1, MSH2, MSH6, and PMS2 was detected by immunohistochemistry. The associations of MSI‐H and MSI‐L with progression‐free survival (PFS) and overall survival (OS) were assessed by COX models and Kaplan–Meier curves. The correlations of complete response (CR) after R‐CHOP/CHOP chemotherapy with MSI‐H and MSI‐L were examined by univariate and multivariate logistic regression analyses, respectively. 3 of 92 cases (3.2%) were high MSI (MSI‐H), and 9 cases (9/92, 9.8%) exhibited low MSI (MSI‐L). One case with MSI‐H showed negative expression of MSH2 and MSH6. Univariate analysis indicated that MSI‐L was correlated with poor response to R‐CHOP/CHOP chemotherapy in DLBCLs (OR, 0.178; 95% CI, 0.041‐0.776; P = .022). Multivariate analysis showed that MSI‐L was an independent predictive factor for non‐CR to R‐CHOP/CHOP chemotherapy (OR, 0.144; 95% CI, 0.027‐0.761; P = .023). Kaplan‐Meier curves showed that there was a trend that MSI‐H patients had favorable PFS (P = .36) and OS (P = .48), which did not have statistical significance and MSI‐L was not significantly correlated with PFS (P = .24) and OS (P = .52).Our study indicated that there existed MSI‐H and MSI‐L in DLBCLs. MSI‐L could be an independent predictive factor for the chemotherapy response in DLBCLs.
Highlights
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults, accounting for nearly 35% of non-Hodgkin lymphomas.[1]
Multivariate regression analysis showed that the Microsatellite instability (MSI)-L phenotype was an independent predictive factor for non-complete response (CR) to R-CHOP/CHOP chemotherapy, irrespective of the clinicopathologic factors of DLBCLs
Our study demonstrated that Microsatellite instability-low (MSI-L) could be an independent predictor to a noncomplete response of R-CHOP/ CHOP chemotherapy in DLBCLs, which might be used as an important biomarker in DLBCLs
Summary
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults, accounting for nearly 35% of non-Hodgkin lymphomas.[1]. Many cancers encode mutation-associated neoantigens (MANAs), which might be potential determinants of immune checkpoint blockades, like PD-1/PD-L1 blockades.[5,6,7] MMR-deficient cancers have large numbers of MANAs which would stimulate the immune response.[8] Recent studies have demonstrated that dMMR could predict the response to PD-1 inhibitor in 12 different kinds of solid tumors, including cholangio carcinoma, endometrial cancer, neuroendocrine carcinoma, and osteosarcoma and so on.[9] the evaluation of MSI and MMR deficiency has significance in predicting the response to PD-1/PD-L1 checkpoint blockades in various types of cancers. The MSI status and its associations with clinicopathologic features and clinical outcomes in DLBCLs are still largely unknown. In our study, we investigated the MSI status in DLBCLs and examined the correlations between MSI and clinicopathologic features and the clinical outcomes, including chemotherapy response and patient prognosis
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