Loss of p16INK4A expression in low-grade ovarian serous carcinomas

Peter W. Schlosshauer, Liane Deligdisch, Frédérique Penault-Llorca, Delaram Fatemi, Rui Qiao, Shen Yao, Meghan Pearl, Zhen Yang, Tao Sheng, Jianli Dong

Research output: Contribution to journalArticle

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Abstract

According to a tumor progression model, low-grade ovarian serous carcinomas may evolve from serous borderline tumors or micropapillary tumors. We sought to investigate the role of and associations between BRAF mutational status, extracellular signal regulated kinase activation, and p16 expression in various types of ovarian serous tumors. We analyzed 29 typical ovarian serous borderline tumors, 8 micropapillary tumors, 4 low-grade invasive ovarian serous carcinomas, and 24 high-grade invasive ovarian serous carcinomas for the BRAF mutational status at codon 600; in addition, expression levels of the downstream signaling protein extracellular signal regulated kinase and the p16 tumor suppressor protein were assessed by immunohistochemistry. There was a decline in p16 expression from serous borderline tumors to micropapillary tumors with almost complete loss in low-grade invasive carcinomas. High-grade carcinomas had a variable p16 expression pattern. We found a T1799A BRAF mutation in 12 typical serous borderline tumors (41%) and 1 micropapillary tumor (12.5%). No mutations were found in the low-grade and high-grade invasive carcinomas (0%). Among the typical borderline tumors, cases with BRAF mutations tended to have stronger p16 expression compared with cases with wild-type BRAF. No other correlations were identified between the BRAF mutational status and expression levels of the analyzed proteins. Loss of p16 expression may be a pathogenetic factor in the progression from serous borderline tumors to low-grade invasive carcinomas. The divergent molecular profiles support the theory that high-grade carcinomas are unrelated to serous borderline tumors or low-grade carcinomas.

Original languageEnglish (US)
Pages (from-to)22-29
Number of pages8
JournalInternational Journal of Gynecological Pathology
Volume30
Issue number1
DOIs
StatePublished - Jan 2011

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Carcinoma
Neoplasms
Extracellular Signal-Regulated MAP Kinases
Mutation
Tumor Suppressor Proteins
Codon
Protein Kinases
Immunohistochemistry

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Obstetrics and Gynecology
  • Medicine(all)

Cite this

Loss of p16INK4A expression in low-grade ovarian serous carcinomas. / Schlosshauer, Peter W.; Deligdisch, Liane; Penault-Llorca, Frédérique; Fatemi, Delaram; Qiao, Rui; Yao, Shen; Pearl, Meghan; Yang, Zhen; Sheng, Tao; Dong, Jianli.

In: International Journal of Gynecological Pathology, Vol. 30, No. 1, 01.2011, p. 22-29.

Research output: Contribution to journalArticle

Schlosshauer, PW, Deligdisch, L, Penault-Llorca, F, Fatemi, D, Qiao, R, Yao, S, Pearl, M, Yang, Z, Sheng, T & Dong, J 2011, 'Loss of p16INK4A expression in low-grade ovarian serous carcinomas', International Journal of Gynecological Pathology, vol. 30, no. 1, pp. 22-29. https://doi.org/10.1097/PGP.0b013e3181ed89b3
Schlosshauer PW, Deligdisch L, Penault-Llorca F, Fatemi D, Qiao R, Yao S et al. Loss of p16INK4A expression in low-grade ovarian serous carcinomas. International Journal of Gynecological Pathology. 2011 Jan;30(1):22-29. https://doi.org/10.1097/PGP.0b013e3181ed89b3
Schlosshauer, Peter W. ; Deligdisch, Liane ; Penault-Llorca, Frédérique ; Fatemi, Delaram ; Qiao, Rui ; Yao, Shen ; Pearl, Meghan ; Yang, Zhen ; Sheng, Tao ; Dong, Jianli. / Loss of p16INK4A expression in low-grade ovarian serous carcinomas. In: International Journal of Gynecological Pathology. 2011 ; Vol. 30, No. 1. pp. 22-29.
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