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Rizvi M.M.A.,Jamia Millia Islamia University | Alam M.S.,Jamia Millia Islamia University | Alam M.S.,Jazan University | Ali A.,Jamia Millia Islamia University | And 3 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2011

Purpose: PTEN, a tumor-suppressor gene located on chromosome 10q23.3 is implicated in multiple tumors including cervical carcinoma. Methods: We examined 135 cervical cancer specimens for PTEN gene expression and promoter methylation using methylation-specific PCR and immunohistochemistry and also studied the mutation in PTEN gene through PCR-single-stranded conformational polymorphism. PTEN expression and its methylation status were also correlated with clinicopathologic parameters. Results: The results showed an abnormal band on exon 5 and exon 9 of the PTEN gene. In PTEN gene, 61% specimen showed methylation. PTEN methylation was found in 39% cases of stage I, 60% of stage II, and 75% of stages III-IV. The correlation between PTEN methylation and clinical stage was found to be statistically significant (P = 0.003). Nuclear PTEN expression was detected in 84 of 135 (62%) cases of cervical carcinoma, and the remaining 51 of 135 (38%) cases were observed as expressional loss. The loss of PTEN expression was significantly correlated clinical stage (P = 0.001). Loss of PTEN expression was observed in 34 (41%) cases among 83 methylation positive cases, whereas among 52 methylation-negative cases, only 13 (25%) cases were seen as immunostaining negative with the statistically significant value (P = 0.05). Conclusion: Promoter methylation and loss of PTEN expression occur frequently in carcinoma of uterine cervix. Our results suggest that PTEN plays an important role in the carcinogenesis of cervical cancer. © 2011 Springer-Verlag. Source


Alyasiri N.S.,Jamia Millia Islamia University | Mehdi S.J.,Jamia Millia Islamia University | Alam M.S.,Jamia Millia Islamia University | Ali A.,Jamia Millia Islamia University | And 4 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2012

Purpose: The tumor suppressor gene PTEN negatively regulates Akt, a downstream mediator phosphoinositol 3-kinase. Several studies have reported the role of PTEN gene in Akt downregulation and apoptosis induction in different cancers and cell lines. However, the role of loss of PTEN expression in Akt activation and spontaneous apoptosis in oral squamous cell carcinoma clinical specimens is not well established. Methods: We investigated the expression of PTEN and phospho-Akt in 146 formalin-fixed (archived) paraffinembedded oral squamous cell carcinoma tissue sections through immunohistochemical analysis. Programmed cell death (apoptosis) was determined by Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling assay. Results: Sixty-one percent loss of PTEN expression and 68.5% Akt activation was observed in oral squamous cell carcinoma. A significant correlation was found between loss of PTEN expression and Akt activation. Loss of PTEN expression and Akt activation were further orrelated with different clinical parameters and found to be significantly correlated with tumor stage. Apoptotic index was estimated and correlated with PTEN expression and Akt activation. The percentage of apoptotic cells varied from 0.2 to 14.1%. Low apoptotic index was observed in 105 (72%) of samples, and it was found to be significantly related with loss of PTEN expression and phospho-Akt Conclusion: The present study confirms the contribution of loss of PTEN expression in Akt phosphorylation and spontaneous apoptosis suppression in the specimens of oral cancer. Both PTEN and phospho-Akt are likely to be concerned with oral cancer progression and reduced incidence of spontaneous apoptosis © 2011 Springer-Verlag. Source


Alyasiri N.S.,Jamia Millia Islamia University | Ali A.,Jamia Millia Islamia University | Kazim Z.,Jamia Millia Islamia University | Gupta S.,Maulana Azad Institute of Dental science | And 3 more authors.
International Journal of Biological Markers | Year: 2013

Background and aims: Oral cancer is the second most common cancer in men and accounts for 50%-70% of the total cancer mortality in India. PTEN is a tumor suppressor gene that plays a critical role in controlling cell growth and survival. Promoter hypermethylation of the PTEN gene has been reported in many tumors. However, little is known about the associa¬tion between promoter methylation and oral squamous cell carcinoma (OSCC). Therefore, we aimed to detect the role of PTEN hypermethylation in OSCC patients in the Indian population. Methods: Genomic DNA was isolated from 100 fresh oral tumor specimens and was subjected to bisulfite conversion. Methylation-specific PCR was employed on the converted DNA to investigate the methylation status. Results: Of the total cases examined for PTEN promoter methylation we found that 35% were positive and 65% were negative. When evaluated in connection with tumor differentiation it was found that 82% of poorly differentiated, 24% of moderately differentiated and 32% of well differentiated OSCC samples were methylated. Methylation was further correlated with patient age, sex and tumor grade. Interestingly, we found that patient age and grade of differentiation were significantly associated with PTEN promoter methylation (p=0.05 and 0.0019, respectively) while sex was not (p=0.9). Conclusions: The present study underlines the importance of PTEN hypermethylation among Indian OSCC patients. © 2013 Wichtig Editore. Source


Alam M.S.,Jamia Millia Islamia University | Alam M.S.,Jazan University | Ali A.,Jamia Millia Islamia University | Mehdi S.J.,Jamia Millia Islamia University | And 5 more authors.
Tumor Biology | Year: 2012

Definite progress in understanding the etiology of cervical cancer has been achieved, and some types of human papillomavirus have been established as the central cause of cervical cancer worldwide. This study investigates the human papillomavirus infection and its correlation with apoptosis and clinicopathologic characteristics in squamous cell carcinoma of uterine cervix. Human papillomavirus typing was done by type-specific primers for high-risk human papillomavirus using standard polymerase chain reaction method. Programmed cell death (apoptosis) was determined by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay. Human papillomavirus infection in tissue biopsy of cervical carcinoma was detected in 131 of 135 (97%) cases. Among the positive cases of human papillomavirus, 123 (94%) cases were human papillomavirus type 16, and five (4%) cases were human papillomavirus type 18. Out of 135 cervical carcinoma cases, 81 (60%) cases showed presence of apoptosis. The phenomenon of apoptosis was seen slightly higher in squamous cell carcinoma than in adenocarcinoma (40% in squamous cell carcinoma and 33% in adenocarcinoma). The human papillomavirus infection in cervical cancer might not play any role in the occurrence of apoptosis. © 2011 International Society of Oncology and BioMarkers (ISOBM). Source

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