p53 gene mutations are common in uterine serous carcinoma and occur early in their pathogenesis

Hironori Tashiro, Christina Isacson, Ross Levine, Robert J. Kurman, Kathleen R. Cho, Lora Hedrick

Research output: Contribution to journalArticle

Abstract

Uterine serous carcinoma (USC) is an uncommon but aggressive type of endometrial cancer associated with rapid progression of disease and a poor prognosis. Both USC and its recently described putative precursor, endometrial intraepithelial carcinoma (EIC), demonstrate strong p53 overexpression by immunohistochemistry, suggesting alteration of the p53 gene in their pathogenesis. In the present study, we evaluated 21 USCs and 9 EICs for mutations in the p53 gene using direct sequence analysis and found that 90% of USCs and 78% of EICs contain mutations. Significantly, mutations were found in 3 cases of EIC without associated invasive carcinoma and identical mutations were detected in cases with synchronous USC and EIC. Strong p53 immunoreactivity was seen in the majority of USCs and EICs and correlated with p53 gene mutation, although lack of reactivity did not always indicate the absence of a gene mutation. Loss of heterozygosity of chromosome 17p was observed in 100% of USCs and in 43% of EICs, demonstrating that loss of the wild-type p53 allele occurs early in the development of serous carcinoma. Overall, our results reveal that p53 mutations are very common in USC and EIC. The presence of p53 gene mutations in EIC further suggests that p53 alteration plays an important role early in the pathogenesis of serous carcinoma, possibly accounting for its aggressive biological behavior.

Original languageEnglish (US)
Pages (from-to)177-185
Number of pages9
JournalAmerican Journal of Pathology
Volume150
Issue number1
StatePublished - Jan 21 1997

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Tashiro, H., Isacson, C., Levine, R., Kurman, R. J., Cho, K. R., & Hedrick, L. (1997). p53 gene mutations are common in uterine serous carcinoma and occur early in their pathogenesis. American Journal of Pathology, 150(1), 177-185.