Purpose: Many studies have evaluated the role of high levels of microsatellite instability (MSI) as a prognostic marker and predictor of the response to chemotherapy in colorectal cancer (CRC); however, the results are not conclusive. The aim of this study was to analyze the prognostic significance of high levels of MSI (MSI-H) in CRC patients in relation to fluorouracil-based chemotherapy. Experimental Design: In three different institutions,1,263 patients with CRC were tested for the presence of MSI, and CRC-specific survival was then analyzed in relation to MSI status, chemotherapy, and other clinical and pathologic variables. Results:Two hundred and fifty-six tumors were MSI-H (20.3%): these were more frequently at a less advanced stage, right-sided, poorly differentiated, with mucinous phenotype, and expansive growth pattern than microsatellite stable carcinomas. Univariate and multivariate analyses of 5-year^specific survival revealed stage, tumor location, grade of differentiation, MSI, gender, and age as significant prognostic factors. The prognostic advantage of MSI tumors was particularly evident in stages II and III in which chemotherapy did not significantly affect the survival of MSI-H patients. Finally, we analyzed survival in MSI-H patients in relation to the presence of mismatch repair gene mutations. MSI-H patients with hereditary non^polyposis colorectal cancer showed a better prognosis as compared with sporadic MSI-H; however, in multivariate analysis, this difference disappeared. Conclusions: The type of genomic instability could influence the prognosis of CRC, in particular in stages II and III. Fluorouracil-based chemotherapy does not seem to improve survival among MSI-H patients.The survival benefit for patients with hereditary non^polyposis colorectal cancer is mainly determined by younger age and less advanced stage as compared with sporadic MSI-H counterpart.

Colorectal cancers with high-frequency microsatellite instability show peculiar clinicopathological features and a favorable clinical outcome. We investigated whether the improved prognosis for these cancers is related to the content of activated cytotoxic intraepithelial T lymphocytes. Microsatellite instability and the amount of activated cytotoxic lymphocytes were analyzed according to clinicopathological features, survival, and disease recurrence in 109 right-sided colon carcinomas from 245 consecutive patients with stage II/III colon cancer that underwent radical surgery. High-frequency microsatellite instability was found in 43% of stage II/III proximal colon cancers and was associated with significantly higher numbers of activated cytotoxic lymphocytes. High-frequency microsatellite instability, as well as the content of intratumoral-activated cytotoxic T lymphocytes correlated with improved overall and disease-free survival, particularly in patients with stage III tumors. Multivariate analysis revealed that patients with both features had a risk of death and relapse markedly lower than that associated with microsatellite status or intratumoral cytotoxic lymphocytes separately. The presence of local cytotoxic immune responses is probably the major determinant of the good clinical course of patients with microsatellite unstable colon cancer. Furthermore, high-frequency microsatellite instability coupled with a high content of intratumoral cytotoxic lymphocytes may identify a subset of colon cancer patients with a favorable clinical outcome, particularly in stage III disease.

Immunohistochemical testing for MLH1/MSH2 expression provides useful prognostic information for the management of stage II and III colorectal cancer patients.

To examine the prevalence of depressive symptoms and its relationship with quality-of-life domains in home-care cancer patients at an advanced stage of illness, 86 patients were given psychological tests for depression (Hospital Anxiety Depression Scale) (HAD) and quality of life (EORTC-QLQ-C30) 1 week after admission to the home-care program. Using a proper cut-off score on the HAD-Depression subscale, depressive symptoms were reported by 45% of the patients. The quality of life of depressed patients was more affected than non-depressed patients in the social, emotional, cognitive, and physical domains. Significant correlations were found between depression scores and impairment in most quality-of-life areas. These findings support the importance of depression and quality-of-life evaluation in patients with advanced cancer who are followed in a home-care setting. This evaluation is needed to provide patients, their families, and caregivers with appropriate psychosocial interventions.

All these data strongly indicate that MTAs represent a distinct pathologic entity, with specific histologic appearance and peculiar clinical and genetic features. These tumors need to be classified separately from other poorly differentiated colorectal carcinomas.

Detection of colorectal carcinomas with highfrequency microsatellite instability (MSI-H

Assessment of MSI status is an essential step in the genetic characterization of large bowel carcinomas and identifies a subset of tumors with distinct clinical, pathologic, and biologic features.

In conclusion, RT and nivolumab can be combined, obtaining a benefit in overall survival and progression-free survival, without an increase in acute toxicities in pretreated advanced NSCLC patients. Prospective studies are needed to confirm these results.