Malik W Ahmed1, Mahmood A Kayani1, Ghulam Shabbir2, Syed M Ali3, Wajih-Ud-Din Shinwari3, Ishrat Mahjabeen1. 1. Cancer Genetics Lab, Department of Biosciences, COMSATS Institute of Information Technology, Islamabad - Pakistan. 2. Department of Plastic and Reconstructive Surgery, Pakistan Institute of Medical Sciences (PIMS), Islamabad - Pakistan. 3. Department of ENT, Pakistan Institute of Medical Sciences (PIMS), Islamabad - Pakistan.
Abstract
INTRODUCTION: PTEN is part of large family of tyrosine phosphatases and has been found inactivated in a wide variety of human cancers. AIMS: In the present study we have tried to determine the association of the expression patterns of this gene with carcinogenesis. METHODS: First, a systematic review was carried out to ascertain the importance of the PTEN gene and its role in carcinogenesis. In the second phase, a case-control study was designed using different expression analysis techniques. Expression of PTEN mRNA was analyzed using reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Significantly downregulated expression of PTEN was observed in patients with head and neck cancer (HNC) compared to adjacent normal-tissue controls. These results were confirmed with quantitative polymerase chain reaction (qPCR). Significant downregulation of the gene was observed in HNC patients compared to adjacent normal-tissue controls. PTEN expression was correlated with different histopathological parameters of the study cohort by Spearman's correlation coefficient and a significant negative correlation was observed with pT stage (r = -0.271*; p<0.02) and grade (r = -0.228*; p<0.02) of HNC tissues. Furthermore, the expression variations of PTEN were correlated with the expression pattern of the proliferation marker Ki-67. Significantly (p<0.008) upregulated expression of Ki-67 was observed in HNC patients compared with adjacent normal-tissue controls This upregulation of Ki-67 was confirmed at the protein level by immunohistochemistry in HNC patients. When Spearman's correlation was carried out a significant negative correlation was observed between PTEN and Ki-67 (r = -0.230*; p<0.03). CONCLUSIONS: Our data suggest that downregulation of PTEN and overexpression of Ki-67 may contribute to the initiation and progression of HNC.
INTRODUCTION:PTEN is part of large family of tyrosine phosphatases and has been found inactivated in a wide variety of humancancers. AIMS: In the present study we have tried to determine the association of the expression patterns of this gene with carcinogenesis. METHODS: First, a systematic review was carried out to ascertain the importance of the PTEN gene and its role in carcinogenesis. In the second phase, a case-control study was designed using different expression analysis techniques. Expression of PTEN mRNA was analyzed using reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Significantly downregulated expression of PTEN was observed in patients with head and neck cancer (HNC) compared to adjacent normal-tissue controls. These results were confirmed with quantitative polymerase chain reaction (qPCR). Significant downregulation of the gene was observed in HNC patients compared to adjacent normal-tissue controls. PTEN expression was correlated with different histopathological parameters of the study cohort by Spearman's correlation coefficient and a significant negative correlation was observed with pT stage (r = -0.271*; p&lt;0.02) and grade (r = -0.228*; p&lt;0.02) of HNC tissues. Furthermore, the expression variations of PTEN were correlated with the expression pattern of the proliferation marker Ki-67. Significantly (p&lt;0.008) upregulated expression of Ki-67 was observed in HNC patients compared with adjacent normal-tissue controls This upregulation of Ki-67 was confirmed at the protein level by immunohistochemistry in HNC patients. When Spearman's correlation was carried out a significant negative correlation was observed between PTEN and Ki-67 (r = -0.230*; p&lt;0.03). CONCLUSIONS: Our data suggest that downregulation of PTEN and overexpression of Ki-67 may contribute to the initiation and progression of HNC.