Kazuma Sakuraba

Downregulation of Mus81 as a novel prognostic biomarker for patients with colorectal carcinoma

The Mus81 gene encodes a critical endonuclease involved in DNA repair and tumor suppression. Our previous study has shown reduced expression of Mus81 in hepatocellular carcinoma and its association with the metastastic potential and prognosis of hepatocellular carcinoma. However, the role of Mus81 in colorectal carcinoma is currently unknown. We therefore carried out the present study to explore the correlation between Mus81 expression and the progression of colorectal carcinoma. Mus81 expression in 92 cases of colorectal carcinoma and matched normal tissues was determined by quantitative real‐time polymerase chain reaction. Our results showed that Mus81 expression in colorectal carcinoma tissues was significantly reduced compared with the corresponding normal tissues (P < 0.001) and the downregulation of Mus81 (decreased by more than 50%) was found in 60.9% (56/92) of colorectal carcinoma. Moreover, Mus81 downregulation correlated significantly to hepatic metastasis (P = 0.019) and a high TNM stage (P = 0.025) of colorectal carcinoma. In addition, the decrease of Mus81 was also detected in 10 cases of hepatic metastasis tissues compared with the corresponding primary colorectal carcinoma tissues (P = 0.016). More importantly, colorectal carcinoma patients with apparent Mus81 downregulation have shown significantly poorer overall survival than those with little Mus81 downregulation (P = 0.0374). Also, multivariable Cox regression analysis identified Mus81 downregulation as an independent prognostic factor for colorectal carcinoma (hazard ratio, 1.678; P = 0.040). In conclusion, the reduced expression of Mus81 is closely related to hepatic metastasis and poor prognosis of colorectal carcinoma, indicating Mus81 as a novel prognostic marker for colorectal carcinoma. (Cancer Sci 2011; 102: 472–477)

Methylation of the WNT5A gene is frequently detected in early gastric carcinoma.

BACKGROUND/AIMS Recently, it has been reported that WNT5A methylation was frequently detected in colorectal cancers. However, the relationship between the WNT5A methylation and the characteristics of gastric cancer remains unknown. METHODOLOGY Methylation status of the WNT5A gene was examined in primary carcinomas and the corresponding normal tissues derived from 38 patients with gastric cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS Aberrant methylation of the WNT5A gene was detected in 7 out of the 38 (18%) primary gastric carcinomas, suggesting that the methylation of WNT5A is observed in gastric carcinomas as well as colorectal ones. The clinicopathological data were correlated with the methylation results. A significant difference was observed in the extent of tumor (p=0.0226). Moreover, a trend was shown towards early TNM stages in methylated tumors (p=0.209). CONCLUSIONS WNT5A was more frequently methylated in early gastric carcinomas.

A Long Survival Case of Metachronous Cerebellar Metastasis that was caused by Gastric Cancer

症例は72歳の男性で, 平成14年8月, MU領域の3型胃癌に対し胃全摘術, 脾合併切除が行われた. 最終診断はMU type3, 98×90mm, tub1, T2 (SS) N0 H0 P0 CY0 M0 stage IB根治度Aであった. 平成15年4月上旬より,「喋りにくい」,「小さい文字が書きづらい」といった症状を自覚するようになり, 同年5月初旬に来院された. 頭部MRI上, 右小脳半球に約35mmのringed enhancementを伴う腫瘤が認められた. 単発であることから腫瘍摘出術が行われた. 病理組織像は高分化型腺癌であり, H.E.染色像, 免疫染色像ともに原発巣とよく一致し胃癌異時性小脳転移と診断された. 術後はTS-1による補助化学療法が行われた. 平成19年2月現在, 再発なく生存中である. 胃癌脳転移はまれな疾患であり, その予後は不良である. 本症例は脳転移診断から3年9か月以上の長期にわたり, 再発なく生存中である極めてまれな症例である.