Dedifferentiated endometrial carcinomas with neuroendocrine features: a clinicopathologic, immunohistochemical, and molecular genetic study.

Abstract

Undifferentiated endometrial carcinoma is an aggressive type of uterine cancer, which is occasionally associated with a low-grade endometrioid carcinoma component. This combination is referred to as "dedifferentiated endometrioid endometrial carcinoma." Neuroendocrine expression may occur in undifferentiated endometrial carcinoma, but its significance in dedifferentiated endometrial carcinomas is unknown. To gain insight into the pathogenesis of these tumors we have analyzed the immunophenotype (ARID1A, MLH1, PMS2, MSH2, MSH6, p53, β-catenin, SMARCB1, synaptophysin, chromogranin A, and CD56) and mutational status (PTEN, KRAS, PIK3CA, TP53 and POLE) of 4 dedifferentiated endometrial carcinomas with strong and diffuse neuroendocrine expression. All tumors demonstrated neuroendocrine expression in ≥70% of the cells in the undifferentiated carcinoma areas. Loss of expression of at least 1 DNA mismatch repair protein was observed in 2 cases, and p53 immunoreaction was aberrant (mutated/inactivated) in one case. All carcinomas were negative for β-catenin and maintained nuclear SMARCB1 (INI1) and ARID1A expression. Three tumors shared identical endometrioid molecular profile (PTEN and/or PIK3CA mutations) in both components. One tumor had POLE exonuclease domain mutation in the undifferentiated component. In one case, TP53 mutation was found exclusively in the undifferentiated component. Two patients died with peritoneal carcinomatosis and abdominal metastases, respectively; one patient died of a renal failure without evidence of disease, and the last patient is alive and free of disease at 3.3 years. Dedifferentiated endometrial carcinomas with neuroendocrine features are clinically and molecularly heterogeneous tumors. Probably, these carcinomas might acquire undifferentiated phenotype through mutations in TP53 and POLE.

• Authors: Iñigo Espinosa, Antonio De Leo, Emanuela D'Angelo, Juan M Rosa-Rosa, Marina Corominas, Alan Gonzalez, José Palacios, Jaime Prat
• Journal: Human pathology (Hum Pathol) Vol. 72 Pg. 100-106 (02 2018) ISSN: 1532-8392 [Electronic] United States
• PMID: 29133142 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• ARID1A protein, human
• Biomarkers, Tumor
• DNA-Binding Proteins
• Nuclear Proteins
• Poly-ADP-Ribose Binding Proteins
• SMARCB1 Protein
• SMARCB1 protein, human
• Transcription Factors
• DNA Polymerase II
• POLE protein, human

Topics

• Adult
• Aged
• Biomarkers, Tumor (genetics)
• Carcinoma, Endometrioid (genetics, pathology)
• DNA Polymerase II (genetics)
• DNA-Binding Proteins
• Endometrial Neoplasms (diagnosis, genetics, pathology)
• Female
• Humans
• Immunohistochemistry (methods)
• Middle Aged
• Mutation (genetics)
• Nuclear Proteins (metabolism)
• Poly-ADP-Ribose Binding Proteins (genetics)
• SMARCB1 Protein (metabolism)
• Transcription Factors (metabolism)
• Uterine Neoplasms (diagnosis, genetics, pathology)