The contribution of the hereditary nonpolyposis colorectal cancer syndrome to the development of ovarian cancer
| Autor: | Susanne Malander, Britta Halvarsson, Ulf Kristoffersson, Åke Borg, Eva Rambech, Mef Nilbert, Mona Ridderheim |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Adult
Oncology congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Colorectal cancer Genes BRCA2 Molecular Sequence Data Genes BRCA1 MLH1 Internal medicine medicine PMS2 Humans Prospective Studies Germ-Line Mutation Adaptor Proteins Signal Transducing Aged Mismatch Repair Endonuclease PMS2 Adenosine Triphosphatases Aged 80 and over Ovarian Neoplasms Base Sequence business.industry Nuclear Proteins nutritional and metabolic diseases Obstetrics and Gynecology Microsatellite instability Cancer Middle Aged medicine.disease Colorectal Neoplasms Hereditary Nonpolyposis Immunohistochemistry digestive system diseases DNA-Binding Proteins MSH6 DNA Repair Enzymes MutS Homolog 2 Protein MSH2 Female Carrier Proteins MutL Protein Homolog 1 Ovarian cancer business |
| Zdroj: | Gynecologic Oncology. 101:238-243 |
| ISSN: | 0090-8258 |
| DOI: | 10.1016/j.ygyno.2005.10.029 |
| Popis: | Objective. Ovarian cancer has one of the highest fractions of hereditary cases. The hereditary breast and ovarian cancer syndrome, primarily due to mutations in BRCA1 and BRCA2, is the main cause of heredity, but also the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome confers an increased risk of ovarian cancer. In order to clarify the contribution of HNPCC to the development of ovarian cancer, we collected data on family history of cancer and characterized MMR function in a consecutive series of 128 tumors unselected for age at diagnosis and previously characterized for BRCA gene mutations. Methods. Expression of the MMR proteins MLH1 PMS2, MSH2, and MSH6 was analyzed by immunohistochemistry using tissue microarray sections. Tumors with reduced staining or loss of staining were also analyzed for microsatellite instability (MSI). Results. Loss of MMR protein expression was identified in 3 ovarian cancers, all of which had a MSI-high phenotype. DNA sequence analysis revealed disease-causing germline mutations (deletions of exons 4-6 in MLHI and a 1-nucleotide deletion in exon 5 of MSH6) in two patients diagnosed at ages 40 and 49 years, both of whom had family histories suggestive of HNPCC. The genetic defect in the third case, which was a 47-year old woman without knowledge about her family history with loss of MLH1/PMS2 expression in the tumor tissue, remains elusive. A family history suggestive of HNPCC was identified in an additional case, but this tumor showed normal, retained MMR protein expression and a microsatellite stable phenotype. Conclusions. About 2% of ovarian cancer is caused by germline mutations in the MMR-genes, a minor proportion as compared to the contribution of the BRCA-genes (11% in the present series). However, identification of HNPCC patients is important since it allows inclusion of high-risk individuals into control programs aimed at preventing the more frequent colorectal and endometrial cancers. Tumors within the HNPCC-spectrum should therefore be included when recording a family history of cancer among patients diagnosed with ovarian cancer. (c) 2005 Elsevier Inc. All rights reserved. (Less) |
| Databáze: | OpenAIRE |
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