Aberrations in the progesterone receptor gene and the risk of recurrent endometrial carcinoma

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Abstract
A case–control study was performed in order to determine whether expression of the progesterone receptor (PR) and/or aberrations of the PR gene contribute to the development of recurrent endometrial carcinoma. Primary tumours from 44 patients with recurrence of stage I endometrial carcinoma (patients) within 3 years after initial treatment were compared with tumours from 44 matched patients who were free of recurrence for a minimum of 3 years (controls). Paraffin wax‐embedded primary tumours (n = 88) and recurrent tumours (n = 32) were analysed immunohistochemically for PR expression. A staining index (SI = 0–9) based on the staining intensity and the number of stained cells was calculated. DNA extracted from paraffin wax‐embedded tissues was subjected to PCR–restriction fragment length polymorphism analysis (PCR–RFLP) for determination of the PROGINS DNA sequence alterations and the +331G/A‐promoter polymorphism. Low PR expression (SI < 1.0) was observed in 7% of primary tumours derived from controls, 25% of primary tumours from patients with recurrence, and 38% of recurrent tumours. The expression of PR was significantly lower in primary tumours from patients with recurrence (SI = 4.0 ± 0.5) than in the tumours in the control group (SI = 5.6 ± 0.5) (T‐test for paired analysis, p < 0.05). The PROGINS and +331G/A‐promoter polymorphism were not related to age at diagnosis, tumour grade or myometrial invasion. The +331G/A‐promoter polymorphism was present in 14% of primary tumours from patients without recurrence, compared with 17% of patients with recurrence. The PROGINS polymorphism was observed in 16% of primary tumours from patients without, and in 34% of patients with, recurrence (OR 2.6; 95% CI: 0.9–7.6). Most interestingly, patients who carried the PROGINS variant and in whom a PR‐expressing tumour was diagnosed were at significantly enhanced risk of relapse (OR 4.7; 95% CI: 1.3–17.1). In conclusion, low PR expression tended to be associated with recurrent disease, and PR expression in tumours from patients carrying the PROGINS allele was predictive of the risk of recurrence. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.