title: Endometrial Endometrioid Carcinoma Metastases Show Decreased ER-Alpha and PR-A Expression Compared to Matched Primary Tumors.
abstract: Patients with endometrial endometrioid carcinoma (EEC) that present with advanced primary disease and develop recurrences have a poor outcome. The phenotype of EEC metastases and recurrences is poorly studied. We evaluated the morphological features and ER-alpha/PRA/p53 immunohistochemical expression of a sample of 45 EEC metastases compared to matched primary tumors. Additionally, we studied methylation levels of ER-alpha/PRA gene promoters. The distribution of histological FIGO grade was significantly different in metastases, which disclosed higher grade than primary tumors (p = 0.005). Mitotic index was significantly lower in metastases compared to matched primary tumors (p<0.001). ER-alpha (p = 0.002) and PRA (p<0.001) median H-scores were significantly lower in metastases than in matched primary EECs, but there was no significant difference concerning p53 expression (p = 0.056). ER-alpha/PRA expression differences did not correlate with differences in metastases morphology. ER-alpha/PRA gene promoter levels were globally low (range: 0% to 11.9%). One case showed higher ER-alpha gene promoter methylation in metastasis compared to matched EEC primary tumor. Regarding PRA, there was a significant higher frequency of its promotor methylation in metastases compared to primary tumors (51.6% vs. 22.7%, p = 0.022). In conclusion, EEC metastatic disease displays phenotypic changes along with ER-alpha and PRA decreased expression compared to primary tumors. ER-alpha and PRA gene promoter methylation seems to play a limited role in the etiology of these alterations. PR expression assessment for hormonal treatment decision of patients with advanced tumors, may be more adequate in metastases than in EEC primary tumors.
authors.affiliation: Department of Pathology, Portuguese Oncology Institute-Porto, Porto, Portugal; Cancer Biology and Epigenetics Group, Research Center of Portuguese Oncology Institute- Porto, Porto, Portugal; Medical Faculty, University of Porto, Porto, Portugal.
authors.forename: Carla
authors.initials: C
authors.lastname: Bartosch
authors.affiliation: Department of Pathology, Portuguese Oncology Institute-Porto, Porto, Portugal; Cancer Biology and Epigenetics Group, Research Center of Portuguese Oncology Institute- Porto, Porto, Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Monteiro-Reis
authors.affiliation: Department of Pathology, Portuguese Oncology Institute-Porto, Porto, Portugal.
authors.forename: Renata
authors.initials: R
authors.lastname: Vieira
authors.affiliation: Department of Pathology, Centro Hospitalar São Joao, Porto, Portugal.
authors.forename: Armindo
authors.initials: A
authors.lastname: Pereira
authors.affiliation: Department of Pathology, Centro Hospitalar São Joao, Porto, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Rodrigues
authors.affiliation: Cancer Biology and Epigenetics Group, Research Center of Portuguese Oncology Institute- Porto, Porto, Portugal; Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar-ICBAS, University of Porto, Porto, Portugal.
authors.forename: Carmen
authors.initials: C
authors.lastname: Jerónimo
authors.affiliation: Medical Faculty, University of Porto, Porto, Portugal; Department of Pathology, Centro Hospitalar São Joao, Porto, Portugal; IPATIMUP, Institute of Molecular Pathology and Immunology, Porto, Portugal.
authors.forename: José M
authors.initials: JM
authors.lastname: Lopes
mesh_terms: D018269:Carcinoma, Endometrioid / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D019175:DNA Methylation / Q000235:genetics; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53