Mismatch repair system in colorectal cancer. Frequency, cancer phenotype, and follow-up.

INTRODUCTION AND AIMS: A frequent task in the study of colorectal carcinomas (CRC) is to identify tumors harboring deficient DNA mismatch repair systems (dMMR), which are associated with microsatellite instability. Given that there is scant information on those tumors in Mexican patients, our aim was to describe their frequency, clinical and pathologic characteristics, and results, which are necessary for future trials. MATERIALS AND METHODS: A consecutive series of CRC patients, treated and followed at a tertiary care center was performed. The clinical and pathologic variables and the risk of hereditary or familial cancer syndrome were retrieved. The original slides and hMLH1, hPMS2, hMSH2, hMSH6 immunohistochemistry were evaluated. Tumors with an absence of at least one protein were considered dMMR. Differences were contrasted, utilizing non-parametric tests. RESULTS: One hundred and forty-four patients were included, with a median age of 65 years. A total of 134/93% patients presented with sporadic CRC, 8/5.6% had a family history of CRC, and 2/1.4% met the diagnostic criteria for hereditary non-polyposis colon cancer, according to the Amsterdam and Bethesda criteria. dMMR tumors were found in 39 patients, distributed among the three groups. They were locally advanced (p<0.001), right-sided, had the mucinous phenotype, and harbored a Crohn's-like lymphoid reaction (all three features, p<0.04). Adjuvant or palliative chemotherapy was administered to 57 (39.6%), concomitant chemoradiotherapy to 24 (16.7%), but 63 (43.8%) patients received no additional treatment to surgery. Five-year follow-up was completed in 131 of the patients and the outcomes alive-with-disease or died-of-disease were more frequently observed in the proficient (pMMR) lesions. CONCLUSIONS: In the present pre-FOLFOX case series, outcomes were better in dMMR CRC than in proficient lesions.

Clinical and pathological factors associated with the development of hepatocellular carcinoma in patients with hepatitis virus-related cirrhosis: a long-term follow-up study.

AIMS: Hepatocellular carcinoma (HCC) represents >90% of primary liver neoplasms and develops mainly in patients with liver cirrhosis. Risk factor identification for the development of HCC in patients with cirrhosis possesses great clinical relevance due to its high incidence and poor prognosis when detected at advanced stages. The aim of this study was to identify HCC development-associated risk factors in a cohort of patients with hepatitis virus-related chronic liver disease and cirrhosis. MATERIALS AND METHODS: Patients with a diagnosis of hepatitis virus-related cirrhosis between January 1980 and January 2000 were included. Patients were followed with an abdominal ultrasound and the determination of alpha-fetoprotein levels, a physical examination, and routine biochemical tests every 3-6 months. The end point of the study was defined as the development of HCC. Liver histology was evaluated according to the French METAVIR Cooperative Study Group (METAVIR) score. RESULTS: Two hundred and eighty-two patients met the inclusion criteria; most of these (86%) had a serologic diagnosis of hepatitis C virus, and only 14% had hepatitis B virus at the time of the diagnosis of cirrhosis, whereas 56 and 37% were classified as Child A and B, respectively, and only 7% as Child C. Histological activity was mild in 59% of patients, and moderate and severe in 41%. The mean annual incidence was 1.87%, and 22 and 35% of patients developed HCC at 10 and 15 years of follow-up, respectively. The diagnosis of HCC was made by histopathology in 37% and by tumoural lesion-associated alpha-fetoprotein elevation confirmed by imaging studies in 63%. In multivariate analysis, we found three variables associated with HCC: moderate to severe histological activity; a platelet count <105x10(3)/mm(3), and alpha-fetoprotein >5 ng/ml. The patients were divided into two groups according to regression coefficient: low and high risk; patients assigned to the low-risk group showed 5-, 10- and 15-year HCC incidences of 3.4, 6.4 and 6.4%, respectively, in contrast to patients from the high-risk group, who showed incidences of 17.8, 33.5 and 56.8%, respectively. CONCLUSIONS: We found three HCC-associated variables: histological activity, platelet count and alpha-fetoprotein levels. Patients considered as high risk for developing HCC must be considered candidates for closer follow-up.