PMS2 Expression With Combination of PD-L1 and TILs for Predicting Survival of Esophageal Squamous Cell Carcinoma

Dongxian Jiang; Qi Song; Xiaojun Wei; Zixiang Yu; Yufeng Liu; Haixing Wang; Xingxing Wang; Jie Huang; Jieakesu Su; Yang Hong; Yifan Xu; Chen Xu; Yingyong Hou

doi:10.3389/fonc.2022.897527

PMS2 Expression With Combination of PD-L1 and TILs for Predicting Survival of Esophageal Squamous Cell Carcinoma

Front Oncol. 2022 Jul 5:12:897527. doi: 10.3389/fonc.2022.897527. eCollection 2022.

Authors

Dongxian Jiang^{1

2}, Qi Song¹, Xiaojun Wei¹, Zixiang Yu¹, Yufeng Liu¹, Haixing Wang¹, Xingxing Wang¹, Jie Huang¹, Jieakesu Su¹, Yang Hong¹, Yifan Xu¹, Chen Xu¹, Yingyong Hou^{1

2}

Affiliations

¹ Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.
² Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China.

Abstract

Background: DNA mismatch repair (MMR) deficiency (dMMR) has been recognized as an important biomarker for immunotherapy in esophageal squamous cell carcinoma (ESCC), along with programmed death ligand 1 (PD-L1) expression and/or tumor-infiltrated lymphocytes (TILs). However, in ESCC, MMR protein assessment has not been well studied at present.

Methods: A total of 484 ESCC tissues treated between 2007 and 2010, in our hospital, were enrolled. Immunohistochemical expression of MLH1, MSH2, MSH6, PMS2, and PD-L1 on tissue microarray specimens and clinicopathological features, including TILs, were analyzed retrospectively.

Results: Out of the 484 studied cases, loss of MLH1, MSH2, MSH6, and PMS2 expression were found in 6.8%, 2.1%, 8.7%, and 4.8% patients, respectively. dMMR was found in 65 patients, 37 cases involved in one MMR protein, 17 cases involved in two proteins, 7 cases involved in three proteins, and 4 cases involved in four proteins. There was no significant survival difference between pMMR (MMR-proficient) and dMMR patients (P>0.05). However, 224 patients with low PMS2 expression had better DFS and OS than 260 patients with high PMS2 expression (P=0.006 for DFS and 0.008 for OS), which was identified as an independent prognostic factor in multivariate analyses. Positive PD-L1 expression was detected in 341 (70.5%) samples. In stage I-II disease, patients with PD-L1 expression had better DFS and OS than those without PD-L1 expression(P<0.05), which was not found in stage III-IV disease. With the ITWG system, 40.1% of cases were classified as high TILs. Patients in the high-TILs group tended to have better DFS (P=0.055) and OS (P=0.070) than those in the low-TILs group and the differences were statistically significant in pMMR, high MSH6, or PMS2 expression cases (P<0.05). Also, high PMS2 expression patients with both PD-L1 expression and high TILs, had similar DFS and OS compared with low PMS2 expression patients (P>0.05), which were much better than other high PMS2 expression patients.

Conclusion: The expression level of MMR proteins could also be used as a prognostic factor in ESCC and PMS2 expression outperformed other MMR proteins for predicting survival. The combination of PD-L1 expression and TILs may lead to more efficient risk stratification of ESCC.

Keywords: DNA mismatch repair protein; PD-L1; PMS2; TILs; esophageal squamous cell carcinoma (ESCC); prognosis.