Abstract

BackgroundEndometrial cancer is the most common gynecologic malignancy in the developed countries. Clinical studies have shown that early stage uterine serous carcinoma (USC) has outcomes similar to early stage high grade endometrioid adenocarcinoma (EAC-G3) than to early stage low grade endometrioid adenocarcinoma (EAC-G1). However, little is known about the origin of these different clinical outcomes. This study applied the whole genome expression profiling to explore the expression difference of stage I USC (n = 11) relative to stage I EAC-G3 (n = 11) and stage I EAC-G1 (n = 11), respectively.Methodology/Principal FindingWe found that the expression difference between USC and EAC-G3, as measured by the number of differentially expressed genes (DEGs), is consistently less than that found between USC and EAC-G1. Pathway enrichment analyses suggested that DEGs specific to USC vs. EAC-G3 are enriched for genes involved in signaling transduction, while DEGs specific to USC vs. EAC-G1 are enriched for genes involved in cell cycle. Gene expression differences for selected DEGs are confirmed by quantitative RT-PCR with a high validation rate.ConclusionThis data, although preliminary, indicates that stage I USC is genetically similar to stage I EAC-G3 compared to stage I EAC-G1. DEGs identified from this study might provide an insight in to the potential mechanisms that influence the clinical outcome differences between endometrial cancer subtypes. They might also have potential prognostic and therapeutic impacts on patients diagnosed with uterine cancer.

Highlights

  • Endometrial carcinoma is the most common gynecologic malignancy in the United States [1]

  • This data, preliminary, indicates that stage I uterine serous carcinoma (USC) is genetically similar to stage I Endometrioid adencoarcinomas (EAC)-G3 compared to stage I EAC-G1

  • We found that the expression difference between USC and EAC-G3, as measured by the number of genes with significantly differential expression, is consistently fewer than that found between USC and EAC-G1

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Summary

Introduction

Endometrial carcinoma is the most common gynecologic malignancy in the United States [1]. While uterine serous carcinomas (USC) represent a minority (3– 10%) of total endometrial cancer cases, they are usually high grade tumors with deep myometrial invasion, lymphovascular involvement, and a more aggressive clinical course [2]. Several reports have suggested that women with early stages USC and clear cell carcinoma have a reasonably good 5- year disease free survival rate of 72%, which was comparable to that of early stage EAC- G3 tumors (76%) [7,8,9]. Clinical studies have shown that early stage uterine serous carcinoma (USC) has outcomes similar to early stage high grade endometrioid adenocarcinoma (EAC-G3) than to early stage low grade endometrioid adenocarcinoma (EAC-G1).

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