Integrating modern approaches to pathogenetic concepts of malignant transformation of endometriosis

  • Authors:
    • Hiroshi Kobayashi
    • Yuki Yamada
    • Naoki Kawahara
    • Kenji Ogawa
    • Chiharu Yoshimoto
  • View Affiliations

  • Published online on: December 21, 2018     https://doi.org/10.3892/or.2018.6946
  • Pages: 1729-1738
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Abstract

In the present study, we summarize the role of the shared and independent (epi)genetic background between endometrioid carcinoma (EC) and clear cell carcinoma (CCC), two histological subtypes of endometriosis-associated ovarian cancer (EAOC). Using the PubMed database, we conducted a literature review of various studies related to the malignant transformation of endometriosis. Both endometriosis and EAOC face potential environmental hazards, including hemoglobin (Hb), heme and free iron, which induces DNA damage and mutations. Although EC is distinguished from CCC due to different morphologies, both represent common environmental profiles and maintain the similar (epi)genomic abnormalities with multiple overlaps and share similar molecular signatures. By contrast, EAOC also has disease-specific gene signatures corresponding with each histological subtype: Estrogen receptor promotes EC cell proliferation (‘go’) and hepatocyte nuclear factor-1β (HNF-1β) induces CCC cell cycle arrest (‘stop’) under oxidative stress conditions. This model underscores a subtype-dependent ‘go or stop’ dichotomy, possibly through better ability to adapt in a changing environment. It was found that cyst fluid Hb and iron concentrations were significantly lower in EAOC when compared to benign ovarian endometrioma (OE), supporting the hypothesis that the redox imbalance plays a key role in the pathogenesis of EAOC. There are at least two phases of iron carcinogenesis and tumor progression: The initial wave of iron-induced oxidative stress and DNA mutations would be followed by the second big wave of subsequent synthesis of the antioxidants, which diminishes cellular oxidative stress capacity, increases apoptosis resistance and promotes tumor initiation and progression. Special emphasis is given to novel pathophysiological concepts of malignant transformation of endometriosis.
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March-2019
Volume 41 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Kobayashi H, Yamada Y, Kawahara N, Ogawa K and Yoshimoto C: Integrating modern approaches to pathogenetic concepts of malignant transformation of endometriosis. Oncol Rep 41: 1729-1738, 2019
APA
Kobayashi, H., Yamada, Y., Kawahara, N., Ogawa, K., & Yoshimoto, C. (2019). Integrating modern approaches to pathogenetic concepts of malignant transformation of endometriosis. Oncology Reports, 41, 1729-1738. https://doi.org/10.3892/or.2018.6946
MLA
Kobayashi, H., Yamada, Y., Kawahara, N., Ogawa, K., Yoshimoto, C."Integrating modern approaches to pathogenetic concepts of malignant transformation of endometriosis". Oncology Reports 41.3 (2019): 1729-1738.
Chicago
Kobayashi, H., Yamada, Y., Kawahara, N., Ogawa, K., Yoshimoto, C."Integrating modern approaches to pathogenetic concepts of malignant transformation of endometriosis". Oncology Reports 41, no. 3 (2019): 1729-1738. https://doi.org/10.3892/or.2018.6946