The expression of programmed cell death ligand 1 in Esophageal Carcinoma patients at Muhimbili National Hospital

Abstract

ABSTRACT Background: Esophageal carcinoma (EC) is a highly aggressive cancer with poor prognosis, which had 511,000 new cases reported globally in 2022. In Tanzania the estimated annual incidence and mortality rates of EC was 7.9% and 11.3% respectively for both sexes, ranking it 2nd among top 3 leading causes of cancer related deaths in the country with a 20% 5-year survival rate. Treatment of EC using Immune checkpoint inhibitors (ICIs’) has demonstrated excellent outcomes in the resolution of tumors when used as monotherapy or in conjunction with radiotherapy and/or chemotherapy medications. The expression of Programmed cell death ligand-1 (PD-L1) on tumor cells is now used as a biomarker to identify patients who might benefit from immunotherapy. Thus, based on EC, investigating PD-L1 immunohistochemistry (IHC) expression in our settings can help identify and evaluate therapeutic candidates and their outcomes as there are no data reported as yet on this area. Broad objective: This study aimed to determine the proportion of PD-L1 IHC expression and its association with clinicopathological factors among patients with EC at Muhimbili National Hospital (MNH). Materials & Methods: This study was a descriptive cross-sectional evaluation of 136 EC cases from January 2019 to January 2023 at MNH in Dar es Salaam, Tanzania. Data regarding age, sex, histological subtypes, tumor location and grade were retrieved from the pathology laboratory archives. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) 27.0. The association between PD-L1 IHC expression and clinicopathological factors was assessed using Fisher's exact test. P≤ 0.05 was considered statistically significant. Results: The mean age of the patients was 58 ±14 years and males accounted for majority 66.9% (91/136) of the study population. Most 56.6% (77/136) of the tumors involved middle third of the esophagus and the predominant (89.0%) histological subtype was Esophageal squamous cell carcinoma (ESCC) (121/136), with majority (55.1%) of the tumors being grade 2 (75/136). PD-L1 IHC expression was observed in 5.1% (7/136) of the cases. No significant association was observed between PD-L1 IHC expression and any clinicopathological factors. Conclusion: This study has shown a low proportion of PD-L1 IHC expression including its lack of association with clinicopathological factors. The variation observed in comparison vi to other studies may be partly explained by several factors, including differences in the assays and antibodies used across studies, as well as sample variability. It is noteworthy however, that in our current study, all PD-L1 positive cases were ESCC and not adenocarcinoma or other subtypes. Thus, these results help inform patients’ selection for PD-L1 IHC staining and subsequently targeted therapy