Takatoshi Matsuyama

MUC12 mRNA expression is an independent marker of prognosis in stage II and stage III colorectal cancer

Distant metastasis is the major cause of death in colorectal cancer (CRC) patients. To identify genes influencing the prognosis of patients with CRC, we compared gene expression in primary tumors with and without distant metastasis using an oligonucleotide microarray. We also examined the expression of the candidate gene in 100 CRC patients by quantitative real‐time reverse transcription PCR and studied the relationship between its expression and the prognosis of patients with CRC. As a result, we identified MUC12 as a candidate gene involved in metastasis processes by microarray analysis. Quantitative real‐time reverse transcription PCR showed that MUC12 expression was significantly lower in cancer tissues than in adjacent normal tissues (p < 0.001). In Stages II and III CRC, patients with low expression showed worse disease‐free survival (p = 0.020). Multivariate analysis disclosed that MUC12 expression status was an independent prognostic factor in Stages II and III CRC (relative risk, 8.236; 95% confidence interval, 1.702–39.849 p = 0.009). Our study revealed the prognostic value of MUC12 expression in CRC patients. Moreover, our result suggests MUC12 expression is a possible candidate gene for assessing postoperative adjuvant therapy for CRC patients.

An intra-abdominal desmoid tumor difficult to distinguish from a gastrointestinal stromal tumor: report of two cases

Desmoid tumors are benign fibroblastic neoplasms with no metastatic potential, but a propensity for local recurrence even after complete surgical resection. These lesions can develop at any site in the body, and commonly occur in the intra-abdominal area. Intra-abdominal desmoid tumors usually occur at the mesentery or retroperitoneum, and may morphologically mimic gastrointestinal stromal tumors (GISTs). Distinguishing between these tumors is important, because the therapies differ substantially, but is often difficult even with the use of CD117 staining. We herein report the cases of two patients with sporadic intra-abdominal desmoid tumors that were differentiated from GIST by immunohistological examination using beta-catenin and CD34. Desmoid tumors specifically express nuclear beta-catenin, and show no expression of CD34. We recommend staining for beta-catenin and CD34 when an intra-abdominal desmoid tumor is suspected.

Robotic-assisted surgery for rectal cancer: Current state and future perspective

Interest in minimally invasive surgery has increased in recent decades. Robotic‐assisted laparoscopic surgery (RALS) was introduced as the latest advance in minimally invasive surgery. RALS has the potential to provide better clinical outcomes in rectal cancer surgery, allowing for precise dissection in the narrow pelvic space. In addition, RALS represents an important advancement in surgical education with respect to use of the dual‐console robotic surgery system. Because the public health insurance systems in Japan have covered the cost of RALS for rectal cancer since April 2018, RALS has been attracting increasingly more attention. Although no overall robust evidence has yet shown that RALS is superior to laparoscopic or open surgery, the current evidence supports the notion that technically demanding subgroups (patients with obesity, male patients, and patients treated by extended procedures) may benefit from RALS. Technological innovation is a constantly evolving field. Several companies have been developing new robotic systems that incorporate new technology. This competition among companies in the development of such systems is anticipated to lead to further improvements in patient outcomes as well as drive down the cost of RALS, which is one main concern of this new technique.

Abstract 4565: Prediction of prognosis by the combination of mutation and methylation in colorectal cancer

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Colorectal cancer (CRC) is among the most common types of cancer in both men and women and is associated with high mortality, particularly at advanced stages. Markers for defining individual risk signatures in CRC patients are of great clinical value, as they may allow for targeted therapies to improve outcomes in CRC patients. Epigenetic alteration such as promoter hypermethylation of gene, as well as genetic abnormality such as gene mutation, occurs frequently during the pathogenesis of human cancers. Recent studies exhibit the increasing observations that both epigenetic and genetic changes combine to determine the phenotype of cancer. Thus, in the present study, we examined KRAS and PIK3CA mutations and the methylation status of BNIP3, SFRP1, and Dkk1, and analyzed the correlation between these molecular alterations and the clinicopathological features of CRC. We aimed to clarify whether a combination of genetic and epigenetic alterations can be used to classify CRC patients in relation to their clinicopathological features and outcomes. Tissue samples from 122 CRC patients who underwent surgical resection were examined. The methylation status of SFRP1 and Dkk1 and the sequences of exon 1 of KRAS gene and exons 9 and 20 of the PIK3CA gene were determined by methylation specific PCR and direct sequencing, respectively, using genomic DNA extracted from paraffin-embedded blocks. Correlation between these factors and clinicopathologic findings/patients survival were examined. As a result, there was a significant correlation between KRAS mutation and BNIP3 (p=0.0004) or Dkk1 (p=0.0009) methylation but not SFRP1 (p=0.114). Although SFRP1 and Dkk1 methylation showed no associations with disease specific survival (DSS) and other clinicopathological findings in CRC patients, BNIP3 was associated with poor DSS (p=0.0149). In CRC without both KRAS and PIK3CA mutation, patients with two or three methylated genes had poorer overall survival compared to those with no or one methylated genes (p=0.0017). To contrary, in the cases of at least one or more mutations, patients with two or three methylated genes tended to have better survival than patients with no methylation. Classifying CRC based on BNIP3, SFRP1, and Dkk1 methylation status and KRAS and PIK3CA mutation may be a clinically powerful predictor of patient outcome. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4565. doi:1538-7445.AM2012-4565