期刊
MODERN PATHOLOGY
卷 23, 期 11, 页码 1477-1485出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/modpathol.2010.145
关键词
FOXL2; granulosa cell tumor; ovarian cancer
类别
资金
- Academy of Finland
- Helsinki University Central Hospital
- Sigrid Juselius Foundation
- Finnish Cancer Organizations
- Cancer Council of Victoria
- National Australia Bank Ovarian Cancer Research Foundation
- Granulosa Cell Tumour of the Ovary Foundation
- National Health and Medical Research Council of Australia
- Dora Lush Biomedical Postgraduate Research Scholarship [441132]
- Victorian Government
- Monash University
Granulosa cell tumors of the ovary represent similar to 5% of malignant ovarian cancers. It has recently been reported that 95-97% of adult granulosa cell tumors carry a unique somatic mutation in the FOXL2 gene. We undertook this study to verify the presence of the FOXL2 Cys134Trp mutation in two geographically independent cohorts of granulosa cell tumors and to examine the expression pattern of FOXL2 in these tumors. A total of 56 tumors with the histological diagnosis of adult granulosa cell tumor from two centers, Melbourne and Helsinki, were examined for the presence of the mutation using direct sequence analysis. Two granulosa cell tumor-derived cell lines, COV434 and KGN, three juvenile granulosa cell tumors and control tissues were also examined. The expression of the FOXL2 gene was determined using quantitative RT-PCR and/or immunohistochemistry. We found that 52 of the 56 adult granulosa cell tumors harbor the mutation, of which three were hemi/homozygous. Of the four cases with wild-type FOXL2 sequence, reappraisal suggests that three may have been misclassified at primary diagnosis. The KGN cells were heterozygous for the mutation, whereas the COV434 cells had a wildtype FOXL2 genotype. The expression levels of FOXL2 were similar across the adult granulosa cell tumors and the normal ovary controls; one mutation-negative granulosa cell tumor had high FOXL2 mRNA levels, whereas the COV434 cells and two of the three juvenile granulosa cell tumors lacked the expression of FOXL2. Our data provide confirmation of the frequent presence of the FOXL2 C134W mutation in adult granulosa cell tumors and demonstrate that the mutation is not associated with altered FOXL2 expression. The mutation analysis may be a useful tool to differentiate particularly between cell-rich diffuse granulosa cell tumors and mitotically active sex cord-stromal tumors. This unique FOXL2 mutation appears to be characteristic of adult granulosa cell tumors. Modern Pathology (2010) 23, 1477-1485; doi:10.1038/modpathol.2010.145; published online 6 August 2010
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据