PROGNOSTIC AND PREDICTIVE SIGNIFICANCE OF PROGRAMMED DEATH LIGAND (PD-L1) AND FOXP3 EXPRESSIONS IN TUMOR CELLS AND TUMOR MICROENVIRONMENT IN OVARIAN CANCER PATIENTS

  • Clinical Oncology and Nuclear Medicine Department , Faculty of Medicine, Zagazig University.
  • Medical Oncology Department, Faculty of Medicine, Zagazig University.
  • Pathology Department, Faculty of Medicine, Zagazig University.
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Background: The microenvironment of epithelial ovarian cancer (EOC) continued to be an important point of research to discover new therapeutic targets for such malignancy. It was discovered that any cells that were in the microenvironment of the EOC may be associated with cancer prognosis like tumor-infiltrating lymphocytes (TILs) and T-regulatory cells (Tregs). The PD-1/PD-L1 pathway was a T-cell checkpoint pathway that sent inhibitory signals to T cells that can inhibit immunity. PDL1, a PD-1 ligand, is detected in lymphocytes, dendritic cells, macrophages and tumor cells. Tregs (mature T lymphocytes) that start in the thymus after stimulation of naïve T cells and responsible for the reduction of autoimmune diseases, but its over production will inhibit endogenous protection against infection and tumors. Forkhead/winged-helix transcription factor box P3 (Foxp3) is an intracellular molecule for Tregs growth and maturation and was found to be the most specific Tregs marker. It was found that Foxp3 is not only found in Treg cells that originated in the thymus but also in malignant cells and its difference in expression can affect the outcome of cancer patients. Aim of our study: was to assess PD-L1 and FOXP3 expression in epithelial ovarian carcinoma a trial to detect their prognostic value and their impact on survival in patients with such type of cancer. Methods: The expressions of PD-L1 and FOXP3 in both tumor cells and stromawere evaluated in sections of 50 paraffin blocks that were retrieved from 50 patients with EOC using immunohistochemistry.We assessed the relation between their expressions, clinicopathological parameters, survival and prognosis of those patients Results: Expression of PDL-1 in tumor cellswas positively correlated with; grade, stage of the tumor, LN metastasis (p=0.001) and histopathological type (0.011), type of surgery and residual disease after surgery (P=0.010).Expression of PDL-1 in TILswas positively correlated with grade (p = 0.033) and stage of the tumor (p = 0.029). Expression of FOXP3in tumor cellswas positively correlated with; age of the patients (p=0.017), grade (p = 0.010), stage of the tumor (p<0.001) and distant metastases (p=0.002).Whereas the expression of FOXP3in TILs was correlated with histological type (P=0.038). Combined low PDL1& FOXP3 expressions in tumor cells were significantly associated withhigher progression free survival (PFS) (p<0.045). There were highly significant statistical relations were found between expression of each marker in tumor cells and Pdl1 in TILs and both Pdl1 &FOXP3 in TILs (p<0.001). There were highly significant statistical relations between expression of both markers in TILs and each one of the following ( Pdl1 in tumor cells (P<0.001), FOXP3 expression in tumor cells (p=0.007) and both markers in tumor cells (P<0.001)) Conclusion: PD-L1 and FOXP3 are considered poor prognostic markers in EOC patients with bad impact on progression free survival.

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[Lobna A. Abdelaziz, Shereen El Shorbagy, Ola M Elfarargy,Ola A. Harb, and Abeer M Abdelbary. (2017); PROGNOSTIC AND PREDICTIVE SIGNIFICANCE OF PROGRAMMED DEATH LIGAND (PD-L1) AND FOXP3 EXPRESSIONS IN TUMOR CELLS AND TUMOR MICROENVIRONMENT IN OVARIAN CANCER PATIENTS Int. J. of Adv. Res. 5 (Jan). 1880-1901] (ISSN 2320-5407). www.journalijar.com

Lobna Abdelaziz Abdelaziz
Lobna A. Abdelaziz

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Article DOI: 10.21474/IJAR01/2958      
DOI URL: https://dx.doi.org/10.21474/IJAR01/2958

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