The conceptual advances of carcinogenic sequence model in high‑grade serous ovarian cancer (Review)

Kobayashi,Hiroshi; Iwai,Kana; Niiro,Emiko; Morioka,Sachiko; Yamada,Yuki; Ogawa,Kenji; Kawahara,Naoki

doi:10.3892/br.2017.955

The conceptual advances of carcinogenic sequence model in high‑grade serous ovarian cancer (Review)

Authors:
- Hiroshi Kobayashi
- Kana Iwai
- Emiko Niiro
- Sachiko Morioka
- Yuki Yamada
- Kenji Ogawa
- Naoki Kawahara
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Affiliations: Department of Obstetrics and Gynecology, Nara Medical University, Kashihara, Nara 634‑8522, Japan
Published online on: July 27, 2017 https://doi.org/10.3892/br.2017.955
Pages: 209-213

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Abstract

The present review focuses on the current status of molecular pathology in high‑grade serous cancer (HGSC) and preneoplastic conditions. This article reviews the English‑language literature on HGSC, precursor, fallopian tubal epithelium, secretory cells, ciliated cells, secretory cell expansion, secretory cell outgrowth (SCOUT), p53 signature, serous tubal intraepithelial carcinoma (STIC), DNA damage and immunohistochemistry in an effort to identify the precursor‑carcinoma sequence in HGSC. The majority of HGSC originates from the fimbriated end of the fallopian tube secretory epithelial cells, while the small part of this disease may develop from ovarian cortical inclusion cyst (CIC). A series of morphological changes from normal fallopian epithelium to preneoplastic to neoplastic lesions were concomitant with the multistep accumulation of molecular and genetic alterations. Recent studies provide a stepwise progression of fallopian tubal epithelium to precursor lesions to carcinoma, with the aid of a ‘secretory cell‑SCE‑SCOUT‑p53 signature‑STIC‑HGSC sequence’ model. Immunohistochemical markers, including p53, STMN1, EZH2, CCNE1, Ki67 and γ‑H2AX, were gradually increased during the SCOUT‑p53 signature‑STIC‑HGSC sequence. Conversely, PAX2 expression was decreased during the early phase of SCOUT development. Potential genes and proteins are involved in the evolutionary trajectory of the precursor‑cancer lineage model. In the present review we examined detailed aspects of the molecular changes involved in malignant transformation from fallopian tube epithelium to HGSC. A precursor condition originating in ‘field cancerization’ may gain a growth advantage, leading to HGSC.

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