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

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

doi:10.3389/fonc.2020.523989

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

Front Oncol. 2020 Dec 15:10:523989. doi: 10.3389/fonc.2020.523989. eCollection 2020.

Authors

Mitchell Acland¹, Georgia Arentz¹, Max Mussared², Fergus Whitehead³, Peter Hoffmann⁴, Manuela Klingler-Hoffmann⁴, Martin K Oehler^{4

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Affiliations

¹ Adelaide Proteomics Centre, School of Biological Sciences, The University of Adelaide, Adelaide, SA, Australia.
² School of Mathematical Sciences, The University of Adelaide, Adelaide, SA, Australia.
³ Cytopathology Department, Clinpath Pathology, Adelaide, SA, Australia.
⁴ Future Industries Institute, Mawson Lakes Campus, University of South Australia, Adelaide, SA, Australia.
⁵ Department of Gynaecological Oncology, Royal Adelaide Hospital, North Terrace, Adelaide, SA, Australia.
⁶ Robinson Research Institute, Discipline of Obstetrics and Gynaecology, Adelaide Medical School, The University of Adelaide, SA, Australia.

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.

Keywords: endometrial intraepithelial carcinoma; high grade serous ovarian carcinoma; proteomics; serous endometrial carcinoma; serous tubal intraepithelial carcinoma.