Detection of human telomerase reverse transcriptase messenger RNA in urine of high risk patients as a non invasive molecular diagnostic tool for urinary bladder cancer in Egyptians

Bladder cancer is an important national health problem as it is the leading cancer in men in Egypt. Cystoscopy and biopsy, currently remains the gold standard procedure for diagnosis, yet, it is invasive and costly. Urinary cytopathology remains to be the only non-invasive alternative method for diagnosis. Although it is tumour specific, yet it has a poor sensitivity, especially for low grade tumours. Detection of Telomerase enzyme in exfoliated urinary cells is a potentially good molecular diagnostic marker in bladder cancer, since the catalytic subunit of this enzyme [hTERT] proved to be essential for cellular immortality and oncogenesis. The study comprised 39 patients [36 with urothelial carcinomas and 3 cases were squamous cell carcinoma] with bladder cancer and 22 non cancer control [including 14 patients with benign urological disorders and 8 healthy volunteers]. The urine sample was split into two aliquots one was used to undertake RNA extraction and hTERT/GAPDH RT-PCR semi-quantitative assay and the second for cytological examination. Cystoscopy was considered the reference standard for the identification of bladder cancer. The hTERT/GAPDH RT-PCR test showed significantly higher diagnostic sensitivity than cytology [84% Vs. 75% p<0.008] for confirmed UCC, particularly for low grade non-muscle invasive UCC [82% Vs. 64% p<0.005]. On combining the two tests a sensitivity of 95% was obtained. A positive hTERT expression was detected 4-5 months earlier than cystoscopic evidence of recurrence in 2 patients during their follow up. In this pilot study, detection of hTERT expression in urine has shown to be a more sensitive marker for diagnosis of bladder cancer than cytology. The combination of urinary hTERT mRNA with cytological testing augments the sensitivity for the non-invasive early diagnosis of bladder cancer. This finding warrants further extended study to validate the potential role of hTERT expression as a diagnostic non invasive tool for high risk patients and detection of recurrence in bladder cancer in Egypt

study of the androgen receptor gene polymorphism and the level of expression of the androgen receptor in androgenetic alopecia among Egyptians

Androgenetic alopecia [AGA] occurs in men and women. The nature of the genetic predisposition to androgenetic alopecia is still unresolved. The aim of the work is to study the genotype of the androgen receptor gene [Stui polymorphism] and its relationship to AGA in a case control study and to determine the level of androgen receptor expression [AR] in the balding scalp relative to the non-balding scalp area. This study was conducted on one hundred individuals; 60 cases with AGA [36 males and 24 females] and 40 age and sex matched control patients [20 males and 20 females]. Stui restriction fragment length polymorphism [RFLP] of exon 1 was detected by PCR based assay using genomic DNA of subjects with AGA and controls. Immunohistochemical detection of the androgen receptor [AR] using antihuman AR antibody was implemented to compare its level in the balding scalp and in the non-balding area in individuals having AGA. Analysis of Stul restriction fragment length polymorphism in exon 1 of the androgen receptor [AR] gene revealed a relatively commoner incidence of the cut allele in males with AGA relative to age and sex matched controls [the association was of border line significance p = 0.07. Interestingly, all persons who had maternal uncles suffering from AGA had the Stui cut variant of AR gene [p = 0.03 using Chi square test]. Semiquantitative immunohistochemical analysis of AR in the bold scalp biopsies showed higher expression in the level of AR than the non bold bioposies within the same individual. To the best of our knowledge this is the first study of AR gene polymorphism and AR expression in AGA amongst Egyptians. This study contributes in the understanding of the molecular pathogenesis of AGA which could help in finding better therapeutic alternatives for such trait in the future