Molecular Classification of Gastric Cancer With Emphasis on PDL-1 Expression: The First Report From Iran

Abstract

Background: Gastric cancer is one of the lethal cancers and there is no effective treatment for these patients and still, 5-year survival rate is about 25% to 30%. Finding reliable biomarkers for early-stage diagnosis, targeted therapy, and survival prediction is a priority in this cancer. Objectives: In this study we were trying to know about the molecular classification of gastric cancers in a group of patients from the South of Iran. Patients and Methods: In a cross sectional study, 50 specimens of gastric cancer were selected that have enough tissue to be stained by immunohistochemistry (IHC). IHC was performed for Her-2, mismatch repair genes (MLH-1, MSH-2, MSH-6, and PMS-2), and PDL-1. Frequency of positive makers was compared with survival and outcome. Results and Conclusion: In our study, deficient MMR (dMMR) was detected in 4 patients (8.0%). PD-L1 expression in tumor cells (TC) was observed in 1 of 4 cases (25%) with PMS2 loss. However, PD-L1 in TCs and TILs (tumor infiltrating lymphocytes) was negative in 1 case with MLH1 loss and in 3 of 4 cases with PMS2 loss, which was not statistically significant. All of our 50 cases were positive for MSH2 and MSH6, 24% of which showed TCs with PDL-1 expression and 32% of them in TIL. HER2 was positive in 2 (2/50, 4.0%) cases, among which all of the cases were positive for PD-L1 expression in TCs and TILs, respectively. However, in HER2-negative group, 26.2% (11/42) and 28.6% (12/42) of tumors were positive for PD-L1 in TCs and TILs, respectively. The expression rate of PD-L1 in HER2 negative TCs was significantly higher than that in HER2 positive TCs ( P = .033). Immunohistochemistry for Her-2 was equivocal in 6 cases (12.0%) none of which expressed PD-L1 in tumor cells. In our study minimum and maximum survival times from detection of gastric cancer were 1 and 87 months, respectively. The mean ± SD and median ± SD of overall survival time were 30.69 ± 4.88 and 18 ± 1.45 months, respectively. One and 3-year survival rates of 40% and 24%, respectively. PD-L1 expression was not associated with survival, but its expression was associated with intestinal type Lauren classification and negative HER-2. PD-L1 positivity in tumor cells or tumor infiltrating lymphocytes was not an independent prognostic factor in gastric cancer.

HER2-Positive Gastric Cancer: The Role of Immunotherapy and Novel Therapeutic Strategies

“…Molecular classification might increase the complexity and costs of diagnosis; however, it provides valuable information necessary to select targeted treatment that may increase the survival of gastric cancer patients [23,24].…”

“…In gastric cancer, PD-L1 CPS ≥ 1 generally defines PD-L1-positive tumors [62]. Some studies have reported significantly higher PD-L1 expression rates in HER2negative tumors [24,63], while other studies reported opposite findings [64,65] or found no differences in PD-L1 expression between HER2-positive and negative tumors [7,66]. These discrepancies may be due to the heterogeneity of the populations studied, differences in the scoring methods, or in the monoclonal antibodies used for detection.…”

HER2-positive Gastric Cancer: The Role of Immunotherapy and Novel Therapeutic Strategies

“…Molecular classification might increase the complexity and costs of diagnosis, however, it provides valuable information necessary to select targeted treatment that may increase the survival of gastric cancer patients [7,8].…”

“…In gastric cancer, PD-L1 CPS ≥ 1 generally defines PD-L1-positive tumors [41]. Some studies have reported significantly higher PD-L1 expression rates in HER2negative tumors [8,42], while other studies reported opposite findings [43,44] or found no differences in PD-L1 expression between HER2-positive and negative tumors [7,45]. These discrepancies may be due to the heterogeneity of the populations studied, differences in the scoring methods, or in the monoclonal antibodies used for detection.…”