Proteomic Analysis of Pre-Invasive Serous Lesions of the Endometrium and Fallopian Tube Reveals Their Metastatic Potential.

Mitchell Acland,Max Mussared,Manuela Klingler-Hoffmann,Georgia Arentz,Fergus Whitehead,Peter Hoffmann,Martin K Oehler

doi:10.3389/fonc.2020.523989

Abstract

Serous endometrial cancer (SEC) and high grade serous ovarian cancer (HGSOC) are aggressive gynecological malignancies with high rates of metastasis and poor prognosis. Endometrial intraepithelial carcinoma (EIC), the precursor for SEC, and serous tubal intraepithelial carcinoma (STIC), believed to be the precursor lesion for HGSOC, can also be associated with intraabdominal spread. To provide insight into the etiology of these precancerous lesions and to explore the potential molecular mechanisms underlying their metastatic behavior, we performed a proteomic mass spectrometry analysis in a patient with synchronous EIC and STIC. Through histological and molecular identification of precancerous lesions followed by laser capture microdissection, we were able to identify over 450 proteins within the precancerous lesions and adjacent healthy tissue. The proteomic analysis of STIC and EIC showed remarkable overlap in the proteomic patterns, reflecting early neoplastic changes in proliferation, loss of polarity and attachment. Our proteomic analysis showed that both EIC and STIC, despite being regarded as premalignant lesions, have metastatic potential, which correlates with the common presentation of invasive serous gynecological malignancies at advanced stage.

Highlights

Endometrial cancer (EC) is the 6th most common cancer in women worldwide and is the most common gynecological malignancy [1]
453 proteins were detected across the 4 tissue types (369 proteins in the serous tubal intraepithelial carcinoma (STIC), 110 proteins in healthy tubal epithelium, 428 proteins in Endometrial intraepithelial carcinoma (EIC), and 162 proteins in healthy endometrial epithelium (Supplementary Table 1)
By investigating the gene expression corresponding to proteins in our data set which are enriched in specific gynecological tissues, we aimed to investigate the connection between preneoplastic lesions of the endometrium and tube with subtypes of endometrial cancer as defined by the TCGA

Summary

Introduction

Endometrial cancer (EC) is the 6th most common cancer in women worldwide and is the most common gynecological malignancy [1]. Serous endometrial carcinoma (SEC) is a highly aggressive malignancy [8]. It represents only 10% of EC cases [9, 10] but is responsible for 39% of EC related deaths [11] and is frequently diagnosed at late stage when prognosis is poor [9, 10]. The current model of SEC development suggests that it evolves from a pre-neoplastic lesion in atrophic endometrium called endometrial glandular dysplasia (EmGD) [12, 13]. This lesion progresses further into endometrial intraepithelial carcinoma (EIC) and, into SEC [14]

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Discussion

Conclusion