The purpose of the current study was t o characterize the role of PTEN in malignant transforma tion and to evaluate the significance of mutated PTEN exons as prognostic markers in the carcinogenesis of endometrial hyperplasia.A comparison of PTEN mutations as pro gnostic markers with former investigated prognosticators was also intended.Histological material from 68patie nts with endometrial hyperplasia and 10-20years of follo w -up of whom 18later developed cancer was examined.PCR amplification and DNA sequencing were performed,s creening the most frequently mutated exons 5a -8b of th e PTEN gene.Mu-tations were demonstrated in 13.2%o f the patients.Of the patients with cancer development,f ive showed to have PTEN mutations corresponding to 28%.Of the patients remaining without carcinoma,only 8%had PTEN muta-tions(P =0.04).In total,there were three missense,three nonsense,and four frameshift mutations,and twice as many mutations leading to a trunca ted protein(six)than mutations altering one amino acid in the entire protein(three).Mutations were distributed in the f ollowing man-ner:three in exon 5a,two in exon 5b,t wo in exon 6,two in exon 7,and one in exon 8b.Only muta tions in exons 6,7,and 8a were connected with cancer d evelopment or co-existing cancer and six out of seven mutations within these exons were frameshift or nonsense mu tations.Our results showed thatmutations in the PTEN gen e were statistically more frequent in cases with cancer development or coex-isting cancer.Although the specifi city was acceptable,the sensitivity of PTEN mutations was to o low to make it suit-able as a tumor marker(sensitivity of 27%and specificity of 91%)in clinical practice.
展开▼
