Microsatellite instability is associated with the histological features tumor in nonfamilial colorectal cancer

Centro Ricerche Neoplasie Apparato Gastroenterico L. Novello, Ospedale San Giovanni Vecchio, Torino, Italy.
Cancer Research (Impact Factor: 9.33). 12/1996; 56(23):5470-4.
Source: PubMed

ABSTRACT Replication errors (RERs) at microsatellite loci were examined in 46 specimens of nonfamilial colorectal cancer. Somatic microsatellite alterations in at least two genetic loci, D11S904, D13S175, D2S123, and D10S197, consistent with a RER(+) phenotype were found in four cases (8.7%). Six additional cases (13%) showed alterations at a single locus. Mucinous differentiation was observed in 3 of 4 (75%) adenocarcinomas with a RER(+) phenotype and only in 19% (8 of 42) of RER(-) adenocarcinomas (P < 0.05). A distinct cap of inflammatory cells at the advancing edge of the tumor and Crohn's-like reaction in peritumoral stroma were histologically identified in 50 and 25% of RER(+) and in 5 and 0% of RER(-) tumors, respectively (P < 0.05). Also, the plexiform pattern of growth of carcinoma turned out to be significantly associated with the RER(+) phenotype (P < 0.05). Mucinous differentiation and stromal inflammatory reactions are frequent features of hereditary nonpolyposis colorectal cancer in which germ-line mutations of mismatch repair genes cause genetic instability. Our results indicate that a link exists between such histological features and somatic genetic instability consistent with a RER(+) phenotype also in nonfamilial colorectal cancer.

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Available from: Gigliola Reato, Sep 28, 2015
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    • "Poorly differentiated colorectal carcinomas are quite rare, comprising only 3 – 5% of all colorectal carcinomas. It is well known that mucinous carcinoma is frequently observed in colorectal cancer with genetic instability, but the difference in genetic pathways between these histological types is mostly unknown because of the very small number of cases (Risio et al, 1996). "
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    ABSTRACT: It has recently become clear that CDH13 (H-cadherin, T-cadherin) expression is frequently silenced by aberrant methylation in colorectal cancers and adenomas. In this study, we investigated the methylation status of CDH13 gene and detected aberrant promoter methylation in 27 of 84 (32%) colorectal cancers. We then correlated the results with the clinicopathological features of affected patients. We found a significant difference in histology (P=0.0053) when we compared the CDH13 methylation of poorly differentiated colorectal cancers to that of differentiated ones. This result suggested that poorly differentiated colorectal cancers specifically exhibited CDH13 methylation, and since CDH13 might be responsible for selective cell recognition and adhesion, inactivation of CDH13 could lead to the formation of scattered carcinoma cells in these cancers.
    British Journal of Cancer 04/2004; 90(5):1030-3. DOI:10.1038/sj.bjc.6601647 · 4.84 Impact Factor
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    • "So we were not able to determine whether these tumours showed partly chromosomic instability. MSI positive tumours have particular clinical and histopathological features (Lothe et al, 1993; Thibodeau et al, 1993, 1998; Kim et al, 1994; Risio et al, 1996; Rüschoff et al, 1997; Jass et al, 1998; Gafa et al, 2000). In our series, the different features associated with MSI status conformed with the characteristics described in the literature: the presence of a mucinous component, rather poor differentiation, a Crohn's like lymphoid stromal reaction and a trend towards a tumour of a larger size. "
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    ABSTRACT: Microsatellite instability has been proposed as an alternative pathway of colorectal carcinogenesis. The aim of this study was to evaluate the interest of immunohistochemistry as a new tool for highlighting mismatch repair deficiency and to compare the results with a PCR-based microsatellite assay. A total of 100 sporadic proximal colon adenocarcinomas were analysed. The expression of hMLH1, hMSH2 and hMSH6 proteins evaluated by immunohistochemistry was altered in 39% of the cancers, whereas microsatellite instability assessed by PCR was detected in 43%. There was discordance between the two methods in eight cases. After further analyses performed on other tumoural areas for these eight cases, total concordance between the two techniques was observed (Kappa=100%). Our results demonstrate that immunohistochemistry may be as efficient as microsatellite amplification in the detection of unstable phenotype provided that at least two samples of each carcinoma are screened, because of intratumoural heterogeneity. British Journal of Cancer (2002) 87, 400–404. doi:10.1038/sj.bjc.6600474 © 2002 Cancer Research UK
    British Journal of Cancer 09/2002; 87(4):400-4. DOI:10.1038/sj.bjc.6600474 · 4.84 Impact Factor
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    ABSTRACT: The understanding of mammalian mismatch repair (MMR) gene function has been accelerated as a result of progress on several fronts. First, the biochemical analysis of MMR has been advanced by the production of purified human MMR proteins which will eventually allow reconstitution of MMR activity in vitro. Second, a wealth of clinical studies on colon cancer patients have begun to allow correlations to be made among MMR mutations, tumor types, therapeutic approaches and clinical outcomes. Finally, new unexpected meiotic phenotypes have been associated with mutations in certain mouse MMR genes.
    Current Opinion in Genetics & Development 07/1997; 7(3):364-70. DOI:10.1016/S0959-437X(97)80150-5 · 7.57 Impact Factor
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