Infiltrating T lymphocytes and programmed cell death protein-1/programmed death-ligand 1 expression in endometriosis-associated ovarian cancer

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Authors:

Camilla Nero, M.D., Ilaria Romito, M.D., Saveria Spadola, M.D., Alessia Romito, M.D., Luigi Carlo Turco, M.D., Francesco Cosentino, M.D., Maria De Ninno, M.D., Ursula Catena, M.D., Alessandra De Cicco Nardone, M.D., Rossana Moroni, Ph.D., Gianfranco Zannoni, M.D., Ph.D., Anna Fagotti, M.D., Ph.D., Giovanni Scambia, M.D., Ph.D.

Abstract:

Objective

To characterize T lymphocyte infiltration and programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) expression in early-stage endometriosis-associated ovarian cancer (EAOC), ovarian endometriosis (OE), atypical endometriosis (AE), and deep endometriosis (DE).


Design

Case-control, retrospective study.


Setting

Research University Hospital.


Patient(s)

A total of 362 patients with a histologic diagnosis of EAOC, OE, AE, or DE were identified between 2000 and 2019 from Fondazione Policlinico Universitario Agostino Gemelli IRCCS and Gemelli Molise SpA tissue data banks. A 1:1 propensity score-matched method yielded matched pairs of 55 subjects with EAOC, 55 patients with OE, 12 patients with AE, and 42 patients with DE, resulting in no differences in family history of cancer, parity, and use of oral contraceptives.


Intervention(s)

Immunohistochemistry assays using the following primary antibodies: CD3+; CD4+; CD8+; PD-1; and PD-L1.


Main Outcome Measure(s)

To characterize T lymphocyte infiltration and PD-1/PD-L1 expression in 4 different endometriosis-related diseases.


Result(s)

Endometriosis-associated ovarian cancer cases displayed significantly higher levels of PD-1/PD-L1 expression compared with all other endometriosis-related diseases (vs. OE vs. AE vs. DE). Moreover, a significantly lower count of infiltrating T lymphocytes was observed in EAOC cases compared with OE ones. Finally, one-third of OE cases showed a cancer-like PD-1/PD-L1 expression profile.


Conclusion(s)

Endometriosis-associated ovarian cancer is characterized by higher levels of PD-1/PD-L1 expression compared with benign endometriosis-related diseases. This profile was found in one-third of clinically benign cases, suggesting that it develops early in the carcinogenesis process.

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility┬« is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.