Villin1, a novel diagnostic marker for cervical adenocarcinoma

The number of new cervical adenocarcinoma (AD) cases has risen slowly, however, its histological similarity to other tumor types and the difficulty of identifying the site of the original tumor makes the diagnosis of cervical AD particularly challenging. We investigated a novel molecular biomarker f...

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Bibliographic Details
Published in:Cancer biology & therapy 2009-06, Vol.8 (12), p.1146-1153
Main Authors: Nakamura, Etsuko, Iwakawa, Mayumi, Furuta, Reiko, Ohno, Tatsuya, Satoh, Toyomi, Nakawatari, Miyako, Ishikawa, Ken-ichi, Imadome, Kaori, Michikawa, Yuichi, Tamaki, Tomoaki, Katoh, Shingo, Kitagawa, Tomoyuki, Imai, Takashi
Format: Article
Language:English
Subjects:
Adenocarcinoma - genetics
Adenocarcinoma - metabolism
Adenocarcinoma - pathology
Aged
Aged, 80 and over
Binding
Biology
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Bioscience
Calcium
Cancer
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - metabolism
Carcinoma, Squamous Cell - pathology
Cell
Cell Line, Tumor
Cycle
Disease-Free Survival
Female
Gene Expression Regulation, Neoplastic
Genes, Tumor Suppressor
Humans
Kaplan-Meier Estimate
Landes
Middle Aged
Organogenesis
Proteins
Tissue Array Analysis
Uterine Cervical Neoplasms - genetics
Uterine Cervical Neoplasms - metabolism
Uterine Cervical Neoplasms - pathology
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Summary:The number of new cervical adenocarcinoma (AD) cases has risen slowly, however, its histological similarity to other tumor types and the difficulty of identifying the site of the original tumor makes the diagnosis of cervical AD particularly challenging. We investigated a novel molecular biomarker for cervical AD through the integration of multiple methods of genomic analysis. Tumor samples in discovery set were obtained from 87 patients who underwent radiotherapy, including 31 cervical AD. Microarray analysis and quantitative polymerase chain reaction analysis were performed to screen a candidate diagnostic molecule for cervical AD, and its clinical significance was investigated by immunohistochemical analysis (IHC). We found a difference between biopsy samples of AD and squamous cell carcinoma (SCC) in the expression and genomic copy number of Villin1 (VIL1), which maps to 2q35. IHC revealed 14 VIL1-positive tumors; 13 cervical AD and 1 small cell carcinoma of cervix, while none of SCC or endometrial AD was VIL1-positive. Kaplan-Meier survival curves revealed worse disease-free survival in VIL1-positive tumors. The marker was validated by newly enrolled 65 patients, and VIL1 positive staining showed 52% of sensitivity and 100% of selectivity for cervical AD. In conclusion, we have identified VIL1 as a novel biomarker of cervical AD. VIL1, a major structural component of the brush border cytoskeleton, which was recently found to be an epithelial cell-specific anti-apoptotic protein. Our study suggests the existence of a subtype of cervical tumors which are VIL1 positive with poor radioresponse.
ISSN:1538-4047
1555-8576
DOI:10.4161/cbt.8.12.8477