Microsatellite instability and its associations with the clinicopathologic characteristics of diffuse large B‐cell lymphoma

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.

An unusual case of microsatellite instability–high/deficient mismatch repair (MSI-H/dMMR) diffuse large B-cell lymphoma revealed by targeted gene sequencing

“…However, recent analyses of NGS data showed that MSI-H in non-Hodgkin lymphoma, including DLBCL, is either extremely rare (<1%) or not a feature of these tumors [ 4 – 7 ]. In contrast to those reports, a study using a commercial MSI kit, based on eight mononucleotide repeat markers and two pentanucleotide repeat markers, identified MSI-H and microsatellite instability–low (MSI-L) in 3% (3/92) and 10% (9/92) of DLBCLs, respectively [ 9 ]. According to the authors, patients with MSI-H DLBCL tended to have a better prognosis than those with microsatellite stable DLBCL, although the difference was not significant [ 9 ].…”

“…In contrast to those reports, a study using a commercial MSI kit, based on eight mononucleotide repeat markers and two pentanucleotide repeat markers, identified MSI-H and microsatellite instability–low (MSI-L) in 3% (3/92) and 10% (9/92) of DLBCLs, respectively [ 9 ]. According to the authors, patients with MSI-H DLBCL tended to have a better prognosis than those with microsatellite stable DLBCL, although the difference was not significant [ 9 ]. They also reported that MSI-L DLBCL was associated with a poor response to chemotherapy [ 9 ].…”

“…According to the authors, patients with MSI-H DLBCL tended to have a better prognosis than those with microsatellite stable DLBCL, although the difference was not significant [ 9 ]. They also reported that MSI-L DLBCL was associated with a poor response to chemotherapy [ 9 ]. These results suggest that MSI status could be a useful biomarker for DLBCL.…”

“…However, the prevalence of MSI is highly variable across cancer types; it is very low (< 1%) in non-Hodgkin lymphomas, except immunodeficiency-related lymphomas [4][5][6][7][8]. MSI has been studied widely in colon cancer and endometrial cancer but only rarely in diffuse large B-cell lymphoma (DLBCL) [4,8,9]. The clinical relevance of MSI in patients with DLBCL, in terms of prognostic significance or as a predictor of the response to immune checkpoint blockade, is unknown.…”

Predicting Responses to Checkpoint Inhibitors in Lymphoma: Are We Up to the Standards of Solid Tumors?

“…MSI and MMR status have not been defined in various hematologic malignancies, but deficient status is seen in approximately 9% in cHL, 40 8% in PMBCL, 83 and 0.3% to 3.2% in DLBCL. 84,90 Their association with response to checkpoint blockade is currently unknown in lymphoma as no patients with lymphoma were represented in the trials involving MSI-H/dMMR cancers.…”