Expression of the p53 Target Wig-1 Is Associated with HPV Status and Patient Survival in Cervical Carcinoma |
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Authors: | Li-Di Xu Susanne Muller Srinivasan R Thoppe Fredrik Hellborg Lena Kanter Mikael Lerner Biying Zheng Svetlana Bajalica Lagercrantz Dan Grandér Keng Ling Wallin Klas G Wiman Catharina Larsson Sonia Andersson |
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Institution: | 1. Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Karolinska University Hospital-Solna, Stockholm, Sweden.; 2. Department of Women''s and Children''s Health, Division of Obstetrics and Gynecology, Karolinska University Hospital-Solna, Stockholm, Sweden.; 3. Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital-Solna, Stockholm, Sweden.; Rush University Medical Center, United States of America, |
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Abstract: | The p53 target gene WIG-1 (ZMAT3) is located in chromosomal region 3q26, that is frequently amplified in human tumors, including cervical cancer. We have examined the status of WIG-1 and the encoded Wig-1 protein in cervical carcinoma cell lines and tumor tissue samples. Our analysis of eight cervical cancer lines (Ca Ski, ME-180, MS751, SiHa, SW756, C-4I, C-33A, and HT-3) by spectral karyotype, comparative genomic hybridization and Southern blotting revealed WIG-1 is not the primary target for chromosome 3 gains. However, WIG-1/Wig-1 were readily expressed and WIG-1 mRNA expression was higher in the two HPV-negative cervical cell lines (C33-A, HT-3) than in HPV-positive lines. We then assessed Wig-1 expression by immunohistochemistry in 38 cervical tumor samples. We found higher nuclear Wig-1 expression levels in HPV-negative compared to HPV positive cases (p = 0.002) and in adenocarcinomas as compared to squamous cell lesions (p<0.0001). Cases with moderate nuclear Wig-1 staining and positive cytoplasmic Wig-1 staining showed longer survival than patients with strong nuclear and negative cytoplasmic staining (p = 0.042). Nuclear Wig-1 expression levels were positively associated with age at diagnosis (p = 0.023) and histologic grade (p = 0.034). These results are consistent with a growth-promoting and/or anti-cell death function of nuclear Wig-1 and suggest that Wig-1 expression can serve as a prognostic marker in cervical carcinoma. |
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