SIGNIFICANCE OF PROGRAMMED DEATH LIGAND-1 IN INVASIVE SQUAMOUS CELL CARCINOMA OF UTERINE CERVIX

Abstract

Background : Cervical cancer is the most common gynecological malignancy worldwide. Integration of viral (HPV) genome into the host genome with acquisition of other genetic abnormalities results in malignant transformation. PD-L1 is a trans-membrane protein assumed to play a major role in suppressing the adaptive arm of immune system. In carcinoma patients, PD-L1 is primary ligand of PD-1 and is expressed on tumor cells. The binding of PD-L1 to PD-1 leads to an immunosuppressive effect allowing the tumor to escape immune destruction. Normal cervical epithelium do not express PD-L1. PD-L1 expression noted in cervical tumour cells suggest that the PD-1/PD-L1 pathway can be a potential immunotherapy target in patients with cervical cancer. Information on the clinical importance of PD-L1 expression in cervical cancer is largely lacking. Aim of the study: To determine the expression of PD-L1 in Invasive Squamous cell carcinoma of uterine cervix and its correlation with clinico-pathological parameters. Methods: The study was conducted in Department of Pathology in Collaboration with Department of Obstetrics and Gynaecology, Sri Devaraj Urs Medical College attached to R.L Jalappa Hospital and Research centre, Tamaka, Kolar during the period of July 2016 to June 2018. The study included 90 cases of Cervical carcinoma diagnosed by histopathology. Immunohistochemistry was performed using antibodies against PD-L1. Expression of PD-L1 xvii was documented and analyzed. PD-L1 expression was correlated with clinic-pathological parameters of carcinoma cervix. Statistical analysis was performed using Chi-square test or Fischer’s exact test. A p value of less than 0.05 was considered substantially significant. Results: The average age of presentation of cervical carcinoma cases in current study was 52 years. Maximum number of Cervical Carcinoma cases were observed in the age group of 40-49 years (31.1%) followed by 50-59 years (24.4%) and 60-69 years (22.22%). As the age increases PD-L1 positive expression increases. 83.3% (10 out of 12 cases in 70-79 year age group) showed PD-L1 positive expression with p value of 0.037. Maximum number of cases were of moderately differentiated SCC around [47 cases (52.2%)] followed by poorly differentiated SCC [28 cases (31.1%)] and well differentiated SCC [15 cases(16.7%)]. Positive expression of PD-L1 was observed maximum in moderately differentiated SCC [40 cases (85.1%) out of 47]. In well differentiated SCC 8 cases (53.3%) out of 15 showed PD- L1 positive expression followed by poorly differentiated carcinoma in which 12 cases out of 28 cases(42.9%) showed PD-L1 positive expression with p value <0.001, there was statistical significant difference found between histological grading and PD-L1 expression. No statistical significant correlation was seen between PD-L1 expression and various other clinico-pathological parameters such as parity, clinical findings, lymph node status, staging, size of lesion and overall survival. Conclusion: This study observed 66.6% expression of PD-L1 in cervical squamous cell carcinoma. The findings in present study further support the role for investigation of anti-PD-L1/PD-1 immunotherapies for the treatment of PD-L1-positive cervical tumors. Future clinical trials xviii with larger population size and multi-centric studies can prove the role of PD-L1 in treatment of cervical carcinoma.