Endometrial Carcinoma: Molecular Cytogenetics and Transcriptomic Profile

Abstract

Endometrial carcinomas (ECs) are histologically classified as endometrioid and nonendometrioid tumors, with each subgroup displaying different molecular profiles and clinical outcomes. Considerable biological and clinical heterogeneity exists within this scheme, however, reflecting its imperfection. We aimed to gather additional data that might help clarify the tumors’ pathogenesis and contribute toward a more meaningful classification scheme. In total, 33 ECs were examined for the presence of chromosomal aberrations, genomic imbalances, pathogenic variants, microsatellite instability, and expression profiles at both gene and miRNA levels. Chromosome 1 was the most frequently rearranged chromosome, showing a gain of all or part of the long arm. Pathogenic variants were found for PTEN (53%), PDGFRA (37%), PIK3CA (34%), and KIT (31%). High microsatellite instability was identified in 15 ECs. Comparing tumors and controls, we identified 23 differentially expressed genes of known importance in carcinogenesis, 15 genes involved in innate and adaptative immune responses, and altered expression of 7 miRNAs. miR-32-5p was the most upregulated. Our series showed a high degree of heterogeneity. Tumors were well-separated from controls, but there was no clear-cut separation between endometrioid and nonendometrioid ECs. Whether this means that the current phenotypic classification is of little relevance or if one still has not detected which genomic parameters to enter into correlation analyses remains unknown.

Identification and subsequent validation of transcriptomic signature associated with metabolic status in endometrial cancer

“…To date, only a few transcriptomic studies have focused on the regulation of cancer metabolism. Specifically, prognostic gene signatures using transcription factors and immune-related mechanisms were studied 14 – 17 .…”

Comparison of Methods for Testing Mismatch Repair Status in Endometrial Cancer

“…MSI is determined based on the pattern observed in a subset of MS and requires expertise for its interpretation. As stated in the introduction, new approaches recently evolved, with differences in their performance, would merit further evaluation in EC; the most traditional and widely used for decades have been the Bethesda panel (composed of two mononucleotide and three dinucleotide loci) and other commercially available panels consisting of five mononucleotides (like Promega 1.2) [14][15][16].…”

“…The most used panels are the Bethesda one, which analyzes two mononucleotides (BAT-25 and BAT-26) and three dinucleotides (D5S346, D2S123, and D17S250) repeats, and alternatively, the one covering five mononucleotide repeats (BAT-25, BAT-26, NR-21, NR-24, and NR-27), included in the Promega MSI Analysis version 1.2 [12,13]. Additional PCR-based kits based on these MS or alternative panels, as well as other options based on PCR and high-resolution melting or chip microfluidic electrophoresis, are now available as alternative MSI analysis options [14][15][16].…”

Application of NGS molecular classification in the diagnosis of endometrial carcinoma: A supplement to traditional pathological diagnosis

“…Inconsistencies also arise, as in our study, which may be related to intratumor heterogeneity due to curettage of a small segment of tumor. As illustrated by Marta Brunetti, 53 EC tumors are characterized by a high degree of tumoral heterogeneity.…”