Expression of the p53 target Wig-1 is associated with HPV status and patient survival in cervical carcinoma.
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.
Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Karolinska University Hospital-Solna, Stockholm, Sweden.
Li-Di
LD
Xu
Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska University Hospital-Solna, Stockholm, Sweden.
Susanne
S
Muller
Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital-Solna, Stockholm, Sweden.
Srinivasan R
SR
Thoppe
Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Karolinska University Hospital-Solna, Stockholm, Sweden.
Fredrik
F
Hellborg
Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Karolinska University Hospital-Solna, Stockholm, Sweden.
Lena
L
Kanter
Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Karolinska University Hospital-Solna, Stockholm, Sweden.
Mikael
M
Lerner
Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital-Solna, Stockholm, Sweden.
Biying
B
Zheng
Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Karolinska University Hospital-Solna, Stockholm, Sweden.
Svetlana Bajalica
SB
Lagercrantz
Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Karolinska University Hospital-Solna, Stockholm, Sweden.
Dan
D
Grandér
Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Karolinska University Hospital-Solna, Stockholm, Sweden.
Keng Ling
KL
Wallin
Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Karolinska University Hospital-Solna, Stockholm, Sweden.
Klas G
KG
Wiman
Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Karolinska University Hospital-Solna, Stockholm, Sweden.
Catharina
C
Larsson
Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska University Hospital-Solna, Stockholm, Sweden.
Sonia
S
Andersson
D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056426:Genetic Loci / Q000235:genetics; D006801:Humans; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D027383:Papillomaviridae / Q000502:physiology*; D011379:Prognosis; D016601:RNA-Binding Proteins; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000821:virology*
D002352:Carrier Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; C436503:ZMAT3 protein, human