Kenzo Yanagita

Undetectable expression of hMLH1 protein in sporadic colorectal cancer with replication error phenotype

PURPOSE: Four DNA mismatch repair genes have been identified as being susceptible genes for hereditary nonpolyposis colorectal cancer. Deficiency of one of the mismatch repair genes causes the replication error phenotype in more than 80 percent of patients with hereditary non-polyposis colorectal cancer and in 10 to 30 percent of patients with sporadic colorectal cancer. To determine which mismatch repair gene is lacking the function in patients with replication error-positive colorectal cancer, several approaches have been used at the nucleic acid and protein levels. We studied replication error in 40 samples of randomly selected colorectal cancers and expression of hMSH2 and hMLH1 proteins analyzed by immunoblot in the tumor and normal tissues of the replication error-positive and replication error-negative samples. MATERIALS AND METHODS: Frozen tumor and normal tissues were obtained from 40 Japanese patients who had colorectal cancer. According to the Amsterdam criteria, those patients were classified as having 39 sporadic and 1 unknown colorectal cancers. Genomic DNA was extracted from tumor and normal tissues for determining replication error with eight microsatellite markers. Expression of hMSH2 and hMLH1 proteins in cell lysates of tumor and normal tissues of 16 patients was analyzed by immunoblot. RESULTS: The replication error phenotype was found in 6 (15 percent) of the 39 sporadic cases. hMLH1 protein was not detected in two of the six replication error-positive tumor tissues and not in the normal tissues, indicating that the tumor cells of the two patients had severe mutations in both alleles of thehMLH1gene. Another four replication error-positive and ten replication error-negative tumors and normal tissues expressed hMLH1 protein. hMSH2 protein was detected in all samples. CONCLUSION: hMLH1 protein was undetectable in the two tumor tissues of the six replication error-positive samples of sporadic colorectal cancer. The detection procedure used here may have potential use for determining a dysfunctional mismatch repair gene product.

Clinical evaluation of angiography for colorectal cancer with special reference to invasion and hepatic metastasis.

血管造影で大腸癌の壁深達度を客観的に予測する方法はいまだ確立されていないが, 著者らは結腸癌に対し一定の予測基準を用いて診断している.今回, 70例の結腸癌の術前写真を再読影した結果, 平均正診率は85%であり, 動静脈のvasa recta長枝の病的変化が良い指標であった.直腸癌に関しても同様の予測基準を作るべく, 上直腸動脈分枝別読影法を用いて, 110例の術前写真で描出している病的血管変化の部位と組織学的壁深達度の関係を検索した結果, RsおよびRa直腸癌では十分客観的予測が可能であることが判った.腹腔動脈造影の肝転移予測能についても60例で検討したが, 正診率は77%であった.しかし左葉病変の診断能は低かった.