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Expression of immunomodulator programmed death ligand 1 and fork head box protein 3 in squamous cell carcinoma of cervix

Ahmed, Mona M.a; Ibrahim, Hanaa M.a; Balata, Safa A.b; Abdou, Ahmed M.c

Egyptian Journal of Pathology: July 2018 - Volume 38 - Issue 1 - p 52–60
doi: 10.1097/

Background Cervical cancer represents the third most common cancer in women, with higher cancer-related mortality in developing countries. Decrease in the immune response is important for expansion of tumor cells, as it retards the clearance of the malignant cells. Programmed death ligand 1 (PD-L1) is a modulator of immune system. Once it binds to its ligands, it decreases the action of cytotoxic CD8 T cells in response to both viral and/or cancer cells. Fork head box protein 3 (FOXP3) also inhibits the local immune reaction. To improve the prognosis of cervical cancer, novel immunotherapeutic schemes have to be established.

Objective We aimed to investigate PD-L1 and FOXP3 immunohistochemical expressions in squamous cell carcinoma (SCC) of the cervix and their correlation with clinicopathological characters and prognosis.

Patients and methods Archival paraffin-embedded specimens of 31 cases of squamous carcinoma of cervix were examined by immunohistochemistry for FOXP3 and PD-L1. Clinical data were abstracted from the reports of corresponding department.

Results Among the 31 cases of squamous carcinoma of cervix, PD-L1 was expressed in 16 (51.6%) and 17 (54.8%) cases of cancer cervix in tumor cells and tumor-infiltrating lymphocytes, respectively. No significant correlation between PD-L1 expression and clinicopathological characters of cancer cervix was found. FOXP3 was expressed in all cases of cervical cancer, and its expression was related to International Federation of Gynecolology and Obstetrics stage, tumor size, margin, and lymph node metastasis (P<0.001, 0.021, 0.003, and <0.001, respectively). There was no correlation between PD-L1and FOXP3 expressions. PD-L1 expression in both tumor cells and lymphocytes was insignificantly correlated with patient’s survival. In contrast, FOXP3 was associated with progressive disease and reduced overall survival (P<0.001).

Conclusion PD-L1, which is a target of immunotherapy, is expressed in both the carcinoma and tumor-infiltrating lymphocytes in cervical SCC, which suggests that it is a valuable marker to be investigated in these cases. FOXP3 is highly expressed in the cervical SCC and represents an independent poor prognostic marker. There was no correlation between both markers, indicating different pathways in their expression.

Departments of aPathology

bClinical Oncology

cGynecology and Obstetrics, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Correspondence to Mona M. Ahmed, MD, Department of Pathology, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt Tel: +20 100 192 5124; e-mail:

Received December 25, 2017

Accepted October 1, 2018

©2018Egyptian Journal of Pathology
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