MLH1 expression predicts the response to preoperative therapy and is associated with PD-L1 expression in esophageal cancer

Momose, Kazunari; Yamasaki, Makoto; Miyazaki, Yasuhiro; Makino, Tomoki; Takahashi, Tsuyoshi; Kurokawa, Yukinori; Nakajima, Kiyokazu; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro

doi:10.3892/ol.2017.6215

Cited by 16 publications

(23 citation statements)

References 23 publications

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“…This result was similar to those of previous studies, which demonstrated that approximately 85% of MLH1-negative gastric cancers were MSI-H [10,19]. In addition, since immunohistochemistry of MLH1 was shown in a previous report to be a reliable method to detect MMRD and MSI-H [20], MLH1 status evaluated by immunohistochemistry might be a useful alternative to MSI status as a biomarker in gastric cancer.…”

Section: Discussionsupporting

confidence: 91%

Predictive value of MLH1 and PD-L1 expression for prognosis and response to preoperative chemotherapy in gastric cancer

et al. 2019

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Background Microsatellite instability (MSI) and programmed death-ligand 1 (PD-L1) are candidate predictors for the response to immune checkpoint inhibitors, and may predict chemotherapy sensitivity. We investigated the simultaneous expression of mutL homolog 1 (MLH1), a mismatch repair gene, and PD-L1 in gastric cancers. Methods We examined MLH1 and PD-L1 expression in surgical specimens from 285 gastric cancer patients treated with or without preoperative chemotherapy, and assessed the relation between expression results and both histological response and recurrence-free survival (RFS). Results Of 285 patients, 28 (9.8%) and 70 (24.6%) exhibited negative MLH1 and high PD-L1 expression, respectively. Most MLH1-negative tumors (85.7%) showed high MSI, and these tumors exhibited high PD-L1 expression more frequently than MLH1-positive tumors (57.1% vs. 21.0%, P < 0.001). MLH1-negative patients were significantly less likely to respond to preoperative chemotherapy than MLH1-positive patients (16.7% vs. 61.2%, P = 0.005), whereas there was no significant difference between high-and low-PD-L1 expression patients (55.9% vs. 56.6%, P = 0.95). RFS in patients without preoperative chemotherapy was significantly longer in the MLH1-negative group than in the MLH1-positive group (HR 0.30; 95% CI 0.09-0.95; P = 0.030), whereas in patients with preoperative chemotherapy there was no significant difference in RFS between the two groups (HR 0.70; 95% CI 0.30-1.63; P = 0.41). PD-L1 expression was not associated with RFS in patients with or without chemotherapy. Conclusions Loss of MLH1 was associated with chemoresistance and did not prolong survival following neoadjuvant chemotherapy. The strong association between MLH1 and MSI status suggests that immune checkpoint inhibitors may be preferable to conventional chemotherapy for MLH1-negative gastric cancer.

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Section: Discussionsupporting

confidence: 91%

Predictive value of MLH1 and PD-L1 expression for prognosis and response to preoperative chemotherapy in gastric cancer

et al. 2019

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“…Findings about the associations between PD-L1 expression and prognosis of ESCC patients in the previous reports were controversial 19 , 22 , 28 , 29 , 32 - 38 . The majority of investigations reported that PD-L1 expression was associated with unfavorable prognosis of ESCC patients 19 , 29 , 32 - 35 , 37 , 38 . However, a few studies reported the opposite results 22 , 28 , 36 .…”

Section: Discussionmentioning

confidence: 89%

PD-L1 Expression On tumor Cells Was Associated With Unfavorable Prognosis In Esophageal Squamous Cell Carcinoma

Wang¹,

Feng²,

Wang³

et al. 2018

J. Cancer

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Background: Evidence about the association between programmed cell death ligand 1 (PD-L1) expression and prognosis of esophageal squamous cell carcinoma (ESCC) were limited and controversial. Thus, the present study aims to investigate the prognostic value of tumor immune microenvironment (TIM) based on PD-L1 expression and CD8+ T cell infiltration in ESCC tissues.Methods: From September 2008 to March 2010, a total of 146 ESCC patients received radical esophagectomy were retrospectively analyzed in our present study. PD-L1 expression and CD8+ T cell infiltration were evaluated through immunohistochemistry. The clinicopathological characteristics and survival were analyzed.Results: There were 111 male and 35 female. The median age was 59.1 years (37-78 years). The positive rate of PD-L1 expression was 61.7%. The rate of high CD8+ T cell infiltration was 33%. No significant differences were found between clinicopathological features and PD-L1 expression or CD8+ T cell infiltration. PD-L1 expression was significantly associated with poor overall survival (P=0.010). However, CD8+ T cell infiltration was not a prognostic risk factor. Type of TIM was significantly associated with the prognosis of ESCC patients (P=0.021).Conclusions: PD-L1 expression was an independent risk factor for the prognosis of ESCC patients. Immunotherapy may achieve promising outcomes in ESCC patients with type I TIM.

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“…According to the search strategy in our study, we found 3 studies investigated the prognostic value of PD-L1 expression detected by IHC in tumor-infiltrating immune cells of EC. [ 12 , 18 , 20 ] In the study of Zhang et al, [ 12 ] tissue specimens from 344 patients with ESCC were obtained for IHC analysis of PD-L1 expression on tumor-infiltrating immune cells. The results demonstrated that PD-L1 expression on tumor-infiltrating immune cells is an independent prognostic factor in patients with ESCC and patients with positive immune cell PD-L1 expression had improved survival.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of programmed death ligand-1 immunohistochemical expression in esophageal cancer

Guo

2018

Medicine

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Background:It is thought that expression of programmed death ligand-1 (PD-L1) in esophageal cancer (EC) might compromise patient survival. However, the association between PD-L1 expression and survival of patients with EC remains controversial.Methods:A meta-analysis combining eligible published studies was performed to evaluate the effect of PD-L1 expression in tumor cells detected by immunohistochemistry (IHC) on overall survival (OS) and disease-free survival (DFS) in patients with EC, using pooled hazard ratio (HR) with its 95% confidence interval (CI).Results:The pooled HR for 19 eligible studies (18 publications, n = 3306) suggested that PD-L1 overexpression had an unfavorable impact on OS (HR = 1.42, 95% CI: 1.09–1.86). No significant effect of PD-L1 overexpression on DFS was observed, and the combined HR was 1.08 (95% CI: 0.76–1.53) for 12 eligible studies (11 publications, n = 2260).Conclusion:PD-L1 expression in tumor cells detected by IHC was associated with worse OS in EC. However, the prognostic value of PD-L1 expression in tumor cells on OS in EC still needs further large prospective trials to be clarified.

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MLH1 expression predicts the response to preoperative therapy and is associated with PD-L1 expression in esophageal cancer

Cited by 16 publications

References 23 publications

Predictive value of MLH1 and PD-L1 expression for prognosis and response to preoperative chemotherapy in gastric cancer

Predictive value of MLH1 and PD-L1 expression for prognosis and response to preoperative chemotherapy in gastric cancer

PD-L1 Expression On tumor Cells Was Associated With Unfavorable Prognosis In Esophageal Squamous Cell Carcinoma

Prognostic significance of programmed death ligand-1 immunohistochemical expression in esophageal cancer

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