title: Immunohistochemical characterisation of molecular subtypes in endometrial cancer.
abstract: Four molecular subtypes have lately been established in endometrial cancer basing on estrogen receptor (ER), progesterone receptor (PR) and HER2 status: ER+/PR+/HER2+, ER+/PR+/HER2-, ER-/PR-/HER2+ and ER-/PR-/HER2-. The subtypes have shown diversity in terms of prognosis, clinicopathological and molecular characteristics, with ER+/PR+/HER2- and ER-/PR-/HER2+ group exhibiting exceptionally benign and aggressive behavior, respectively. We have further characterized the subtypes in the context of pathways known to drive endometrial carcinogenesis: phosphatidylinositol 3-kinase (PI3K)-AKT pathway (ERBB/PI3K pathway), TP53 system, and the mismatch repair (MMR) mechanism. Analysis of tumor heterogeneity was also included. ER+/PR+/HER2+ was characterized by active ERBB/PI3K pathway occurring in 58% of cases. Subtype ER-/PR-/HER2+ was characterized by the most frequent TP53 mutations (83% of cases). Triple negative phenotype utterly lacked active ERBB/PI3K pathway. Analyzed major pathways rarely correlated with clinicopathologial data but mutated TP53 and retained MMR did correlate with shorter overall survival (both P<0.01). The presence of tumor heterogeneity was most frequent in ER-/PR-/HER2+ subtype (53% of all cases). The presented results further emphasize that the molecular subtype distinction, along with MMR and TP53 status, could be a useful diagnostic tool in guiding individualized therapy.
authors.affiliation: Department of Gynaecology, Gynaecological Oncology and Gynaecological Endocrinology, Medical University of Gdańsk Kliniczna 1a, 80-402 Gdańsk, Poland.
authors.forename: Sylwia M
authors.initials: SM
authors.lastname: Łapińska-Szumczyk
authors.affiliation: Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk Dębinki 1, 80-211 Gdańsk, Poland.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Supernat
authors.affiliation: Department of Pathomorphology, Medical University of Gdańsk Smoluchowskiego 17, 80-214 Gdańsk, Poland.
authors.forename: Hanna I
authors.initials: HI
authors.lastname: Majewska
authors.affiliation: Department of Pathology and Neuropathology, Medical University of Gdańsk Dębinki 1, 80-211 Gdańsk, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Gulczyński
authors.affiliation: Department of Pathomorphology, Medical University of Gdańsk Smoluchowskiego 17, 80-214 Gdańsk, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Biernat
authors.affiliation: Department of Gynaecology, Gynaecological Oncology and Gynaecological Endocrinology, Medical University of Gdańsk Kliniczna 1a, 80-402 Gdańsk, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Wydra
authors.affiliation: Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk Dębinki 1, 80-211 Gdańsk, Poland.
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Żaczek
keywords: ERBB/PI3K pathway; Mismatch Repair system; Molecular subtypes; TP53; endometrial cancer