Abstract
PurposeTo investigate the status of mismatch repair (MMR) and microsatellite instability (MSI) in triple-negative breast cancer (TNBC) and to examine correlations between MMR/MSI status and clinicopathological parameters.MethodsWe retrospectively collected tissue samples from 440 patients with TNBC and constructed tissue microarrays. Protein expression of MLH1, MSH2, MSH6, and PMS2 was detected by immunohistochemistry (IHC). We also analyzed 195 patient samples using MSI polymerase chain reaction (PCR) testing. Correlations between MSI status and clinicopathological parameters and prognosis were analyzed.ResultsThe median age of the cohort was 49 years (range: 24–90 years) with a median follow-up period of 68 months (range: 1–170 months). All samples were positive for MLH1, MSH2, MSH6, and PMS2, except for one sample identified as MMR-deficient (dMMR) by IHC, with loss of MSH2 and intact MSH6 expression. MSI PCR revealed no case with high-frequency MSI (MSI-H), whereas 14 (7.2%) and 181 (92.8%) samples demonstrated low-frequency and absence of MSI events, respectively. The dMMR sample harbored low-frequency instability, as revealed by MSI PCR, and a possible EPCAM deletion in the tumor, as observed from next-generation sequencing. No correlations were detected between MMR or MSI status and clinicopathological parameters, programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) expression, or survival.ConclusionsThe incidence of dMMR/MSI-H is extremely low in TNBC, and rare discordant MSI PCR/MMR IHC results may be encountered. Moreover, MMR/MSI status may be of limited prognostic value. Further studies are warranted to explore other predictive immunotherapy biomarkers for TNBC.
Highlights
Triple-negative breast cancer (TNBC) is characterized by poor prognosis and lack of effective targeted therapies
Universal screening for MMR/MSI status is being recommended in routine oncological care of patients with solid tumors regardless of the cancer’s origin
The purpose of this study was to evaluate the clinical relevance of MMR/ MSI status in Chinese women with TNBC in order to determine the frequency of dMMR/MSI-H and its potential for predicting the outcome of immunotherapy
Summary
Triple-negative breast cancer (TNBC) is characterized by poor prognosis and lack of effective targeted therapies. Most TNBCs are rich in tumor-infiltrating lymphocytes (TILs), the presence of which correlates with tumor immune response activation and sensitivity to chemotherapy, suggestive of better overall survival [1]. Immunotherapy has become an indispensable treatment strategy for cancer, as it has shown effective results across several solid tumors. PD-L1 levels are correlated with TIL levels and the complete response to neoadjuvant chemotherapy. No efficient immunotherapy biomarkers are known for TNBC. PD-L1 was initially regarded as an efficient biomarker to predict the efficacy of immunotherapy, our previous study revealed that its expression is very low in TNBC tumors, in Chinese women [4]. It is important to identify novel immunotherapy biomarkers for TNBC
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