الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Endometrial cancer is the sixth most prevalent cancer among women and the thirteenth cause of mortality in women worldwide. In Egypt, it is the eighth most prevalent cancer in women and the fifteenth cause of mortality in women.
Risk factors of endometrial cancers include old age, early menarche and late menopause, nulliparity, hormonal factors, positive family history and obesity. Endometrial cancer is classified into type I and type II, type I is the most common type and has a good prognosis.
The majority of endometrial cancer patients diagnosed at an early stage had good prognoses. However, a proportion of individuals with low-grade, low-stage cancers experiences recurrence and poor prognosis. So, early detection of these high-risk tumors may aid in the identification of patients who require closer monitoring and further adjuvant treatment. CTNNB1 gene mutation is suggested to be associated with endometrial cancer recurrence. CTNNB1 exon 3 mutations activate the canonical Wnt/β-catenin signaling pathway, which leads to translocation of β-catenin to the nucleus and the activation of a particular transcriptional program leading to development of cancer.
Therefore, this study aimed to study CTNNB1 exon 3 somatic mutations in early stage, low grade endometrial cancer in a cohort of Egyptian patients. This study included 40 patients with early stage endometrial cancer presented to clinical oncology Department at Alexandria University Hospital. They were divided into two groups; recurrent group which included 20 patients with recurrent endometrial cancer who developed metastasis or local recurrence and non-recurrent group which included 20 patients with early stage endometrial cancer with remission for more than 2 years. Samples (formalin fixed paraffin embedded) was obtained from the Pathology departments at Alexandria University.
DNA was extracted from (FFPE) samples using QIAamp DNA FFPE tissue kit, assessment of DNA concentration and quality using NanoDROP 2000 spectrophotometer, preperation of polymerase chain reaction template using DreamTaq Hot Start PCR master Mix and custom made primers then PCR products were assessed by gel electrophoresis. Purification of PCR templet using the QIAquick® PCR Purification & Gel Cleanup Kit. Then the cycle sequencing was done using BigDye™ Terminator v3.1 Cycle Sequencing Kit. Then sample purification was done using BigDye XTerminator ™ purification kit, followed by capillary electrophoresis using Sanger sequencing (Applied Biosystems 3500 Genetic analyzer) and data analysis using Applied Biosystems™ Minor Variant Finder Software.
In the present study, patients with recurrent endometrial cancer showed a significant higher rate of CTNNB1 exon 3 mutations than non-recurrent group. CTNNB1 exon3 mutations were detected in 70 % of recurrent group and in 30 % of non-recurrent group. Patients harbouring CTNNB1 exon 3 mutations had 5 folds increased risk of recurrence than patient without mutation. Upon comparing the genetic variants in both groups, there were 15 genetic variants in recurrent group and 7 genetic variants in non-recurrent group. The most frequent genetic variant in recurrent group was missense variants, followed by synonymous variants then nonsense variant. In non-recurrent group, the most frequent genetic variant was synonymous variants, followed by missense variants. Interestingly, there were eight genetic variants that were only identified in recurrent group, one of them is c.110C>A (p.Ser37Tyr) that was detected in three patients. Another variant is c.98C>T (p.Ser33Phe) variant, which was detected in two patients.