Molecular pathogenesis of endometriosis-associated clear cell carcinoma of the ovary (Review)

Kobayashi
In: Oncology Reports · 2009 · doi:10.3892/or_00000429 · W4297719537
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⚙ AI-generated summary by claude@2026-06, 2026-06-06 ⓘ

This review discusses the molecular pathogenesis of endometriosis-associated ovarian clear cell carcinoma, highlighting oxidative stress from iron and heme leading to genetic damage and alterations in genes like PTEN, APC, p53, and K-RAS.

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This review examines the molecular mechanisms underlying endometriosis-associated ovarian clear cell carcinoma (CCC), using an English-language literature synthesis of studies including LOH/allelic loss, comparative genomic hybridization, mutation, methylation, microarray gene-expression profiling, and proteomics. It highlights that retrograde menstruation or ovarian hemorrhage can introduce pro-oxidant heme and iron, and that iron-dependent oxidative stress in histologically normal ectopic endometrium may drive DNA damage and LOH as a critical carcinogenic factor. LOH studies point to multiple implicated chromosomal regions (5q, 6q, 9p, 10q, 11q, 17q, and 22q), and the review discusses potential involvement of genes including PTEN and APC (early events) and p53, polo-like kinases, Emi1, and K-RAS (late events), while emphasizing that CCC molecular pathology is heterogeneous with possible multiple precursor lesions and pathways. As an overview of existing studies, it does not present new experimental data. This paper is centrally about endometriosis — it specifically reviews the molecular pathogenesis of endometriosis-associated clear cell carcinoma of the ovary.

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Abstract

Epithelial ovarian cancer (EOC) is the leading cause of death in women with gynecological malignancies. Among EOC, clear cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC) differ from the other histological types with respect to their clinical characteristics and carcinogenesis. Both tumor types are often associated with endometriosis. EAC is recently reported to be characterized by K-RAS activation and PTEN dysfunction. However, the molecular changes in CCC remain largely unknown. The aim of this review is to summarize the current knowledge on the molecular mechanisms involved in CCC tumorigenesis. The present article reviews the English language literature for biological, pathogenetic and pathophysiological studies on endometriosis-associated CCC of the ovary. Several recent studies of loss of heterozygosity (LOH), allelic loss, comparative genomic hybridization, mutation, methylation status, microarray gene-expression profiling and proteomics are discussed in the context of CCC biology. Retrograde menstruation or ovarian hemorrhage carries highly pro-oxidant factors, such as heme and iron, into the peritoneal cavity or ovarian endometrioma. A histologically normal ectopic endometrium bears genetic damages caused by iron-dependent oxidative stress. DNA damage or LOH caused by oxidative stress is a critical factor in the carcinogenic process. LOH studies have implicated the involvement of specific chromosomal regions (5q, 6q, 9p, 10q, 11q, 17q and 22q). Furthermore, the PTEN and APC (early event), p53, polo-like kinases, Emi1 and K-RAS (late event) genes may be involved in CCC carcinogenesis. The molecular pathology of CCC is heterogeneous and involves various putative precursor lesions and multiple pathways of development, possibly via genetic alteration by oxidative stress.
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Print ISSN: 1021-335X Online ISSN: 1791-2431 International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease. International Journal of Oncology is an international journal devoted to oncology research and cancer treatment. Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery. Oncology Reports is an international journal devoted to fundamental and applied research in Oncology. Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine. Oncology Letters is an international journal devoted to Experimental and Clinical Oncology. Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology. International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis. Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology. Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition. Publishes open-access research on using epigenetics to advance understanding and treatment of human disease. An International Open Access Journal Devoted to General Medicine. Review - Authors: - Pages: 233-240|Published online on: August 1, 2009https://doi.org/10.3892/or_00000429 - Expand metrics + Epithelial ovarian cancer (EOC) is the leading cause of death in women with gynecological malignancies. Among EOC, clear cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC) differ from the other histological types with respect to their clinical characteristics and carcinogenesis. Both tumor types are often associated with endometriosis. EAC is recently reported to be characterized by K-RAS activation and PTEN dysfunction. However, the molecular changes in CCC remain largely unknown. The aim of this review is to summarize the current knowledge on the molecular mechanisms involved in CCC tumorigenesis. The present article reviews the English language literature for biological, pathogenetic and pathophysiological studies on endometriosis-associated CCC of the ovary. Several recent studies of loss of heterozygosity (LOH), allelic loss, comparative genomic hybridization, mutation, methylation status, microarray gene-expression profiling and proteomics are discussed in the context of CCC biology. Retrograde menstruation or ovarian hemorrhage carries highly pro-oxidant factors, such as heme and iron, into the peritoneal cavity or ovarian endometrioma. A histologically normal ectopic endometrium bears genetic damages caused by iron-dependent oxidative stress. DNA damage or LOH caused by oxidative stress is a critical factor in the carcinogenic process. LOH studies have implicated the involvement of specific chromosomal regions (5q, 6q, 9p, 10q, 11q, 17q and 22q). Furthermore, the PTEN and APC (early event), p53, polo-like kinases, Emi1 and K-RAS (late event) genes may be involved in CCC carcinogenesis. The molecular pathology of CCC is heterogeneous and involves various putative precursor lesions and multiple pathways of development, possibly via genetic alteration by oxidative stress. Copy and paste a formatted citation Spandidos Publications style Kobayashi H, Kajiwara H, Kanayama S, Yamada Y, Furukawa N, Noguchi T, Haruta S, Yoshida S, Sakata M, Sado T, Sado T, et al: Molecular pathogenesis of endometriosis-associated clear cell carcinoma of the ovary (Review). Oncol Rep 22: 233-240, 2009. APA Kobayashi, H., Kajiwara, H., Kanayama, S., Yamada, Y., Furukawa, N., Noguchi, T. ... Oi, H. (2009). Molecular pathogenesis of endometriosis-associated clear cell carcinoma of the ovary (Review). Oncology Reports, 22, 233-240. https://doi.org/10.3892/or_00000429 MLA Kobayashi, H., Kajiwara, H., Kanayama, S., Yamada, Y., Furukawa, N., Noguchi, T., Haruta, S., Yoshida, S., Sakata, M., Sado, T., Oi, H."Molecular pathogenesis of endometriosis-associated clear cell carcinoma of the ovary (Review)". Oncology Reports 22.2 (2009): 233-240. Chicago Kobayashi, H., Kajiwara, H., Kanayama, S., Yamada, Y., Furukawa, N., Noguchi, T., Haruta, S., Yoshida, S., Sakata, M., Sado, T., Oi, H."Molecular pathogenesis of endometriosis-associated clear cell carcinoma of the ovary (Review)". Oncology Reports 22, no. 2 (2009): 233-240. https://doi.org/10.3892/or_00000429

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