title: Expression of PD-1, PD-L1 and PD-L2 is associated with differentiation status and histological type of endometrial cancer.
abstract: Endometrial cancer (EC) is the most frequent gynecological malignancy and a major cause of morbidity and mortality for women worldwide. Programmed cell death protein 1 (PD-1) and its ligands programmed death ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2) have been well studied in lung cancer, melanoma and renal-cell cancer. However, few studies have been performed in EC. The purpose of the present study was to assess the expression of PD-1, PD-L1 and PD-L2 in 35 human normal endometrial tissue samples and 75 human EC tissue samples using immunohistochemical staining. It was found that 61.3% of ECs were positive for PD-1 staining, which was almost exclusively found in the tumor-infiltrating immune cells. By contrast, PD-1 was not expressed in the tumor cells or normal endometrial tissues. It was also found that 14.3% of normal endometria and 17.3% of EC tissues were positive for PD-L1 expression, while 20.0% of normal endometrium and 37.3% of EC tissues were positive for PD-L2 expression; however, there was no statistically significant difference between the normal endometrium and EC tissues. PD-1 expression in the tumor-infiltrating immune cells was more frequently found in the moderately and poorly-differentiated ECs and non-endometrioid (type II) ECs than in the well-differentiated ECs and endometrioid (type I) ECs. Similarly, PD-L1 and PD-L2 expression in the tumor-infiltrating immune cells was more frequently found in the moderately and poorly-differentiated ECs and type II ECs than in the type I ECs. The present findings indicate a possible better outcome for future treatment with anti-PD-1 or anti-PD-L1 antibody-based therapies against these subgroups of endometrial cancers with frequent expression of the PD-1/PD-L1/PD-L2 axis.
authors.affiliation: Department of Obstetrics and Gynecology, Shijiazhuang Maternal and Child Health Care Hospital, Shijiazhuang, Hebei 050000, P.R. China; Department of Structural and Cellular Biology, Tulane University, New Orleans, LA 70112, USA.
authors.forename: Zhongfu
authors.initials: Z
authors.lastname: Mo
authors.affiliation: Department of Obstetrics and Gynecology, Shijiazhuang Maternal and Child Health Care Hospital, Shijiazhuang, Hebei 050000, P.R. China; Department of Structural and Cellular Biology, Tulane University, New Orleans, LA 70112, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Structural and Cellular Biology, Tulane University, New Orleans, LA 70112, USA.
authors.forename: Qiuyang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Structural and Cellular Biology, Tulane University, New Orleans, LA 70112, USA; Department of Thoracic Surgery, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China.
authors.forename: Zhiquan
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Structural and Cellular Biology, Tulane University, New Orleans, LA 70112, USA; Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China; Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Mei
authors.affiliation: Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China; Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Lunxu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Structural and Cellular Biology, Tulane University, New Orleans, LA 70112, USA; Department of Urology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
authors.forename: Shijie
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Pathology, Shijiazhuang Maternal and Child Health Care Hospital, Shijiazhuang, Hebei 050000, P.R. China.
authors.forename: Huina
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Shijiazhuang Maternal and Child Health Care Hospital, Shijiazhuang, Hebei 050000, P.R. China.
authors.forename: Lifei
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Structural and Cellular Biology, Tulane University, New Orleans, LA 70112, USA.
authors.forename: Zongbing
authors.initials: Z
authors.lastname: You
keywords: PD-1; PD-L1; PD-L2; endometrial cancer; immunohistochemistry