2022 Fiscal Year Final Research Report
Screening method for endometrial cancer for women with suspected Lynch syndrome
Project/Area Number |
20K09636
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 56040:Obstetrics and gynecology-related
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Research Institution | National Cancer Center Japan |
Principal Investigator |
Ishikawa Mitsuya 国立研究開発法人国立がん研究センター, 中央病院, 医長 (00306820)
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Co-Investigator(Kenkyū-buntansha) |
吉田 裕 国立研究開発法人国立がん研究センター, 中央病院, 医員 (70750751)
白石 航也 国立研究開発法人国立がん研究センター, 研究所, 部門長 (80609719)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | リンチ症候群 / 生殖細胞系列変異 / 体細胞異常 |
Outline of Final Research Achievements |
We examined germline mutations in all exons of MSH2, MSH6, MLH1, and PMS2 involved in the development of Lynch syndrome in 433 pathologically diagnosed cases of uterine cancer at the National Cancer Center Hospital from 2011 to 2018, and detected pathological variants in 3.7% of cases. To investigate the clinicopathological differences between cases with and without pathological variants, the expression of MMR proteins (MLH1, MSH2, MSH6, PMS2) in tumor tissue was evaluated by immunostaining (IHC) in 433 cases, and 337 cases were evaluable. Of these, 26.7% were revealed to be MMR deficient (dMMR) or MMR proficient (pMMR). However, cases identified as pathological variants in germline mutations did not necessarily show dMMR. Furthermore, somatic mutation analysis was performed separately for hereditary tumors (Lynch syndrome) and non-Lynch syndrome, focusing on dMMR, and found that Lynch syndrome patients had a better prognosis. These may be new prognostic markers.
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Free Research Field |
婦人腫瘍学
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Academic Significance and Societal Importance of the Research Achievements |
本研究を通して、一般的な子宮体がんにリンチ症候群が4%前後含まれていることが明らかになるとともに、生殖細胞系列変異を持つ方が必ずリンチ症候群を伴う病態を反映するわけではないことが分かった。また生殖細胞系列変異を持つ子宮体癌症例は、そうでない症例に比べて予後良好であることも分かった。以上のことから、生殖細胞系列変異を持つ症例と持たない症例では、サーベイランスが異なる可能性が示唆され、新たなバイオマーカーになりうる可能性を示した。
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