Recent advances in our understanding of gynaecological pathology

C Simon Herrington, Christopher P Crum

Research output: Contribution to journalSpecial issuepeer-review

Abstract

The significance of p53 dysfunction in tumour development is undisputed. However, although TP53 mutation is an important event in serous carcinogenesis and is found in virtually all high-grade pelvic serous carcinomas
[3], it is not sufficient for transformation with other events such as those leading to BRCA dysfunction also being important. At the precursor level, it appears that some molecular events associated with serous carcinoma can be both
broadly-distributed and localized. The fimbriated end of the Fallopian tube is uniquely sensitive to inactivation of TP53 within secretory cells (p53 signatures). In fact, in individuals with germ line haplo-insufficiency of TP53 (Li-
Fraumeni syndrome), abundant foci of p53 staining are seen in the distal Fallopian tube. Conversely while other genes, such as PAX2, are inactivated in these serous cancer precursors in the fimbria, loss of PAX2 expression is also seen throughout the Fallopian tube in secretory cell outgrowths (SCOUTs). It is also lost in the endometrium, in both endometrioid and serous neoplasms and their precursors. This endorses a variable range of tissue (or cell) susceptibility for a given molecular pathway disturbance.
Original languageEnglish
JournalThe Journal of Pathology
Issue numberVirtual Issue Number 1
Publication statusPublished - 2012

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