Abstract
Uterine Papillary Serous Carcinoma (UPSC) is an uncommon form of endometrial
cancer comprising 10% of all endometrial carcinomas. It is a highly aggressive
tumour and because of its poor prognosis, it accounts for a disproportionately large
proportion of deaths from endometrial carcinoma. The reason for its aggressive
behaviour is uncertain. The aim of the thesis was to investigate potential mechanisms
of invasion of UPSC, using an immunohistochemical approach, using high-grade
endometrioid endometrial carcinoma (EEC) as a comparator.
An audit of all cases of UPSC diagnosed in South East of Scotland over a 10 year
period confirmed the poor prognosis of UPSC and showed that this was conferred
even in those cases where the tumour was composed of 5% UPSC regardless of the
additional tumour type. It also raised awareness of the need for accurate and
complete surgical staging. Tissue microarrays (TMAs) were created from the central
viable part of the tumour and the invasive edge of UPSC and EEC and were shown
to be valid for studying expression of the markers involved in this study. There was
intertumoural variation in expression of E- and P-cadherin, CD98, matrix
metalloproteases (MMPs) -2 and -9 and ER and PR in both UPSC and EEC. ER
status is known to affect expression of E cadherin, (3 catenin, CD98 and MMPs -2
and -9, and E cadherin levels were decreased and the other protein molecules all
showed higher expression in EEC compared to UPSC. The results are consistent with
the role that oestrogen plays in the development of EEC.
Intratumoural variation in expression of E cadherin, P cadherin, P catenin, CD98,
Galectin-3, MMPs -2 and -9 was demonstrated, supporting the theory of a subclone
of the tumour developing properties necessary for invasion. These data contribute to
the growing body of literature on UPSC, and address diagnostic and treatment
uncertainties for the pathology, surgical and oncological teams.