マイクロサテライト不安定性を示した放射線誘発大腸癌の1例

Radiation-induced Colon Cancer with High Frequency Microsatellite Instability (MSI-H), Report of a Case

要旨　子宮体癌の放射線治療後，照射野内に大腸癌が発生した症例（67歳，女性）を経験した，本症例は，その臨床経過から，遺伝性非ポリポーシス大腸癌（HNPCC）の可能性を考慮する必要があると考えられたため，MSI試験を施行した．その結果，MSIは検索したすべてのlocusにおいて陽性だった．さらに免疫組織化学的検討により，腫瘍部においてhMSH2蛋白の発現消失を認めた．生殖細胞変異を検討した結果，hMSH2遺伝子に遺伝子多型とされるミスセンス変異を認めたが，明らかな病的変異は今のところ見つかっていない．本症例では，経過中に照射野内に3つの腺腫成分を伴う癌が多発しており，さらに背景粘膜には放射線大腸炎の所見とともに，異型腺管が散在していた．MSI陽性を示す放射線誘発大腸癌はまれであり，本症例は放射線二次発癌とミスマッチ修復異常の関連が示された貴重な症例である．

　We report a 67-year-old female with radiationinduced colon cancer which developed 23 years after radiation therapy for cancer of the endometrium. She was strongly suspected to be a case of HNPCC due to her clinical manifestations, i.e. metachronous multiple cancer developed in the endometrium and colon. MSI test and immunohistochemistry for MMR proteins revealed that MSI was highly positive and expression of hMSH2 was lost in the colon cancers. Further, on examining the genetic change, the point mutation, ACG→ATG, responsible for amino acid change, was detected in codon8 (exonl) of the hMSH2 gene. The change, however, could be a polymorphism of this gene and further analyses were necessitated to confirm the genetic background for HNPCC. Interestingly, three cancers with adenoma were located in the mucosa of radiation colitis, in which several atypical glands were also found.

　This is the only case of radiation-induced colorectal cancer with MSI-H in our hospital. Because of our previous studies, we believe that the genetic pathway in carcinogenesis of the radiation-induced colon cancer is different from that of HNPCC, despite their having several kinds of clinical and pathological features in common.