Kazuyoshi Ishibashi

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.

Proximal-type epithelioid sarcoma in a 36-year-old man: Closer immunoelectron-microscopic resemblance of the tumor cells to epithelial cells than to mesenchymal cells

Proximal‐type epithelioid sarcoma (PES) is a rare neoplasm. We report a case of PES that arose in the perineal subcutis of a 36‐year‐old Japanese man who died within 4 months of the first clinical sign, probably due to massive pulmonary metastases. In the present study, we analyzed the tumor obtained at surgery, immunohistochemically, immunoelectron‐microscopically and genetically. Although the tumor cells in the patient expressed both cytokeratin and vimentin immunohistochemically, they showed epithelial characteristics immunoelectron‐microscopically because they had tonofilaments constructed of cytokeratin, not vimentin. In addition, the cytokeratins expressed on the tumor were glandular‐type keratins. These findings indicate that PES may be a form of carcinoma in soft tissue. To ascertain the possible origin of the tumor, we compared the tumor immunohistochemically with fetal tissues. Although notochord and fetal peritoneal mesothelium were similar to the tumor antigenically, we could not confirm the specific origin of the tumor. Furthermore, the p53‐WAF1 pathway did not contribute to tumorigenesis in the patient because the tumor had no mutation in exons 5–8 of the p53 gene and was immunohistochemically positive for WAF1.

Strangulation Caused by a Small Bowel Epiploic Appendage: Report of a Case

While many recent cases of colonic epiploic appendage causing acute abdomen have been reported, such appendages of the small bowel are extremely rare. We present a 59-year-old woman in whom a small bowel epiploic appendage caused volvulus. She presented with abdominal pain and vomiting in the absence of previous abdominal operations. A diagnosis of small bowel obstruction from strangulation was made. Laparotomy disclosed bloody peritoneal fluid and a closed loop of strangulated small intestine. An adherent band composed of an epiploic appendage and intestine had completely encircled a loop of jejunum, leading to obstruction. This band was released, and approximately 80 cm of gangrenous bowel was resected. Four epiploic appendages 5–6 cm in length were attached to the ileum at the mesenteric border, beginning at a point 70 cm proximal to the terminal ileum.

A patient who showed a pathologically complete response after undergoing treatment with XELOX plus bevacizumab for synchronous liver metastasis of grade H2 from sigmoid colon cancer

We herein report the case of a patient who showed a pathological complete response after undergoing chemotherapy with capecitabine, oxaliplatin and bevacizumab. The patient presented with synchronous solitary liver metastasis from sigmoid colon cancer. The maximum diameter of the liver deposit was 5.7 cm and the grade of the liver metastasis was H2 according to the Japanese classification. Deferred hepatectomy after sigmoidectomy was performed, followed by the administration of neoadjuvant chemotherapy. After undergoing sigmoidectomy, the patient received 1,000 mg/m(2) of capecitabine and 130 mg/m(2) of oxaliplatin without bevacizumab as the first cycle of chemotherapy followed by eight cycles of chemotherapy with bevacizumab (7.5 mg/kg) every three weeks. The liver deposit was reduced to 2.2 cm in diameter and the patient showed a partial response to chemotherapy. The patient then underwent metastasectomy of segment 8 of the liver instead of the central hepatectomy that was possibly needed before chemotherapy. Histopathologically, the tumor consisted of fibrous tissue, and no cancer cells were detected in the resected specimen. A pathological complete response in a patient with H2 liver metastasis is considered rare and suggests that capecitabine, oxaliplatin and bevacizumab are efficacious as neoadjuvant chemotherapy.