title: HER2-positive endometrial cancer subtype carries poor prognosis.
abstract: Endometrial cancer (EC) is a hormone-dependent, most frequent malignancy of the female genital tract, yet no molecular subtype classification based receptor status (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [HER2]) has been established so far. Assuming that molecular subtypes might differ fundamentally in EC, we analyzed expression levels of ER, PR, and HER2 with immunohistochemistry and aimed to determine clinical significance of four molecular subtypes: ER+/PR+/HER2+; ER+/PR+/HER2-, ER-/PR-/HER2+, and ER-/PR-/HER2-. The study included 400 formalin-fixed paraffin-embedded primary tumor EC samples which covered all stages of endometrial carcinoma, from IA to IVB. ER-/PR-/HER2+ subtype correlated with the poorest outcome, ER+/PR+/HER2- subtype was associated with the most favorable prognosis (p = 0.002). Molecular subtype division remained an independent prognostic factor in multivariate analysis, accompanying parameters such as diabetes, hypertension, stage, myometrial infiltration, and metastases, all of which yielded hazard ratios between 1.39 and 2.23. ER+/PR+/HER2+ and ER+/PR+/HER2- subtypes had low average TP53 and TOP2A expression levels when compared with ER-/PR-/HER2+ and ER-/PR-/HER2- (both p < 0.00001). Molecular subtypes in EC do show diversity in terms of prognosis, clinicopathological, and molecular characteristics. ER-/PR-/HER2+ subtype exhibit is exceptionally aggressive tumor characteristics. Subtype differentiation might aid prediction of treatment response in EC.
authors.affiliation: Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Lapińska-Szumczyk
authors.forename: Anna
authors.initials: A
authors.lastname: Supernat
authors.forename: Hanna
authors.initials: H
authors.lastname: Majewska
authors.forename: Jacek
authors.initials: J
authors.lastname: Gulczyński
authors.forename: Agata
authors.initials: A
authors.lastname: Luczak
authors.forename: Wojciech
authors.initials: W
authors.lastname: Biernat
authors.forename: Dariusz
authors.initials: D
authors.lastname: Wydra
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Zaczek
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism; D016009:Chi-Square Distribution; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000145:classification* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; C508053:ERBB2 protein, human; C000618811:TOP2A protein, human
keywords: HER2 receptor; endometrial cancer; estrogen receptor; molecular subtypes; progesterone receptor