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Research Article

Genetic Analysis of the Early Natural History of Epithelial Ovarian Carcinoma

  • Bhavana Pothuri equal contributor,

    equal contributor Contributed equally to this work with: Bhavana Pothuri, Mario M. Leitao, Douglas A. Levine

    Affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

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  • Mario M. Leitao equal contributor,

    equal contributor Contributed equally to this work with: Bhavana Pothuri, Mario M. Leitao, Douglas A. Levine

    Affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

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  • Douglas A. Levine equal contributor,

    equal contributor Contributed equally to this work with: Bhavana Pothuri, Mario M. Leitao, Douglas A. Levine

    Affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

    X
  • Agnès Viale,

    Affiliation: Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

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  • Adam B. Olshen,

    Affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

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  • Crispinita Arroyo,

    Affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

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  • Faina Bogomolniy,

    Affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

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  • Narciso Olvera,

    Affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

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  • Oscar Lin,

    Affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

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  • Robert A. Soslow,

    Affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

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  • Mark E. Robson,

    Affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

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  • Kenneth Offit,

    Affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

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  • Richard R. Barakat,

    Affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

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  • Jeff Boyd mail

    jeff.boyd@fccc.edu

    Affiliations: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America

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  • Published: April 26, 2010
  • DOI: 10.1371/journal.pone.0010358

Reader Comments (1)

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p53 and Ki67 data from other studies

Posted by jurgenpiek on 26 May 2010 at 16:46 GMT

With interest we read the article by Pothuri et al (1). They provide further arguments on the hypothesis that ovarian inclusion cysts are important in ovarian carcinogenesis, originally formulated by us (2). However, their findings contradict our own inclusion cyst results as published in 2003 (3).In our study we showed an almost absence of nuclear p53 protein accumulation in both the epithelium lining inclusion cysts as well the as epithelial cells lining the ovarian surface. These findings were consistent in both women harboring a hereditary high risk to develop female adnexal cancers and controls. Also in contradiction with the study of Pothuri et al we found Ki67 expression, reflecting cell proliferation, to be not significantly different expressed between cases and controls. Similar results were found in previous work of Werness et al (4). The reason for these discrepant results are unclear. Theoretically, age is important since the local ovarian hormonal environment is of importance for the expression of both p53 and Ki67 and therefore the so called “oncogenic stress”. The average age in our cohort was relatively high (cases: 48, controls: 55) as in the matched cohort of Werness (cases: 49, controls: 48), but unfortunately Pothuri et al do not provide age data (or any other clinical or histological data) of their study cohort for comparison. It remains therefore to be elucidated what eventually causes cells already harboring multiple genetic hits to develop into invasive carcinomas, as the average age of onset for hereditary adnexal carcinoma is 52 (5).
Jurgen Piek, Ronald Zweemer, Rene HM Verheijen, Paul J van Diest

Reference List

(1) Pothuri B, Leitao MM, Levine DA, Viale A, Olshen AB, Arroyo C et al. Genetic analysis of the early natural history of epithelial ovarian carcinoma. PLoS One 2010;5(4):e10358.
(2) Piek JM, Verheijen RH, Kenemans P, Massuger LF, Bulten H, van Diest PJ. BRCA1/2-related ovarian cancers are of tubal origin: a hypothesis. Gynecol Oncol 2003;90:491.
(3) Piek JM, Verheijen RH, Menko FH, Jongsma AP, Weegenaar J, Gille JJ et al. Expression of differentiation and proliferation related proteins in epithelium of prophylactically removed ovaries from women with a hereditary female adnexal cancer predisposition. Histopathology 2003 July;43(1):26-32.
(4) Werness BA, Afify AM, Eltabbakh GH, Huelsman K, Piver MS, Paterson JM. p53, c-erbB, and Ki-67 expression in ovaries removed prophylactically from women with a family history of ovarian cancer. Int J Gynecol Pathol 1999 October;18(4):338-43.
(5) Goldgar D, Eeles RA, Easton D, Kakhani SR, Piver MS, Piek JM et al. Inherited tumour syndromes; BRCA1 syndrome. In: Tavassoli FA, Devilee P, editors. Tumours of the breast and female genital organs. 1 ed. Lyon: IARC press; 2003. p. 338-51.

No competing interests declared.