Endometrial carcinoma, which is preceded by non-malignant hyperplasia, is the fifth most common cancer in women worldwide.
Book Title: The Role PTEN Mutations in Hyperplasia and Carcinoma of the Endometrium
Author:Johanna Catharina Aletta Jamison
Published on 2013 by
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Book is About: Carcinoma
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Endometrial carcinoma, which is preceded by non-malignant hyperplasia, is the fifth most common cancer in women worldwide. Various genetic alterations appear to be early events in the pathogenesis of endometrial cancer. The PTEN/MMAC1/TEP1 gene is most commonly mutated in endometrioid adenocarcinoma. This gene, on chromosome 10q23, codes for a tumour suppressor protein which displays lipid and dual-specific protein phosphatase activity. It has been implicated in several signal transduction pathways and seems to be involved in the negative regulation of the PI3K-, the MAPK- and the FAK pathways. Studies have shown that caucasian Americans have a 4-fold higher frequency of PTEN mutations than African Americans. An association of PTEN mutation status with clinical outcome has been found, where patients with PTEN mutation-positive endometrial carcinoma had a better prognosis than those without PTEN mutations. It has been hypothesized that the molecular pathogenesis of endometrial carcinoma within Caucasians and Black African groups may be different. The present study aimed to investigate the PTEN gene in caucasians and Black South African women with endometrial hyperplasia and carcinoma. The correlation between the frequency and type of mutations and the pathological features of the cancers (stage and grade) were also assessed. Paraffin embedded tissue samples from patients with endometrial hyperplasia [n=10] and cancer [n=47] were analysed for PTEN mutations using exon-by-exon PCR-SSCP. Thirty-two mutations were detected of which 24 were pathogenic (23 in the adenocarcinomas, one in the hyperplasias). These included 10 frameshift, 7 nonsense, 4 missense and 3 splice site mutations. Pathogenic mutations were located throughout the gene with the highest frequency observed in exon 5 (39.1%: 9/23), followed by exons 1 and 8 (both 17.4%: 4/23). This data does not differ significantly from published findings (P\u003e0.05: x2-test). Pathogenic mutations were present in 54% (20/37) of the endometrioid adenocarcinomas and 10% (1/10) of the hyperplasias. No mutations were detected in the serous papillary cancers and poorly differentiated carcinomas. Fifty-five % (6/11) of tumours from Caucasians and 52% (13/25) of the tumours from Black South Africans had genetic alterations. When comparing the African and caucasian groups there were no significant differences with regards to PTEN mutation frequency (P\u003e0.05: x2-test). Mutations occurred in early and advanced stage endometrial carcinomas, although the majority of the samples were stage 1 endometrioid adenocarcinomas. In the present study no association between the frequency of PTEN mutations and the grade and stage of the endometrial cancer were found (P\u003e0.05: x2-test). To validate these observations, however, a larger sample size representative of all the grades and stages of endometrial carcinoma needs to be analyzed.
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