Dataset Information

Microsatellite instability in poorly differentiated adenocarcinomas of the colon and rectum: relationship to clinicopathological features.

ABSTRACT: BACKGROUND: Poorly differentiated adenocarcinomas of the colon and rectum (Por) feature the worst prognosis among the various types of colorectal carcinomas. Por is highly associated with microsatellite instability (MSI), although MSI is associated with an improved prognosis in colorectal cancers. AIM: To investigate the influence of MSI on clinicopathological features and survival of patients affected by Por. METHODS: 53 patients affected by Por were investigated. DNA extracted from tumour sections and the corresponding normal tissue was analysed by PCR at five microsatellite loci: BAT25, BAT26, D2S123, D5S346 and D17S250. Tumours with alterations at two or more loci were classified as MSI-Por. The others were classified as microsatellite stability (MSS)-Por. The clinicopathological features and survival of patients with MSI-Por and MSS-Por were investigated. RESULTS: Of the 53 patients who were examined, 12 (22.6%) were MSI-Por, whereas 41 (77.4%) were MSS-Por. Significant differences were found between MSI-Por and MSS-Por regarding the following clinicopathological features: age, gender, lymph-node metastasis (MSI-Por: 4/12; MSS-Por: 33/41), TNM stage (MSI-Por: T1/T2/T3/T4 = 2/6/2/2; MSS-Por: 3/3/19/16) and lymphatic invasion (MSI-Por: 4/10; MSS-Por: 27/35). Kaplan-Meier survival curves and log-rank analysis showed that MSI-Por was associated with better prognosis than MSS-Por, although no significant difference was found. CONCLUSIONS: Compared with MSS-Por, MSI-Por is significantly associated with a low incidence of lymph-node metastases and a low stage. This indicates that MSI-Por is a less aggressive subtype.

SUBMITTER: Kazama Y

PROVIDER: S-EPMC1955052 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Microsatellite instability in poorly differentiated adenocarcinomas of the colon and rectum: relationship to clinicopathological features.

Kazama Yoshihiro Y Watanabe Toshiaki T Kanazawa Takamitsu T Tanaka Junichiro J Tanaka Toshiaki T Nagawa Hirokazu H

Journal of clinical pathology 20070601 6

<h4>Background</h4>Poorly differentiated adenocarcinomas of the colon and rectum (Por) feature the worst prognosis among the various types of colorectal carcinomas. Por is highly associated with microsatellite instability (MSI), although MSI is associated with an improved prognosis in colorectal cancers.<h4>Aim</h4>To investigate the influence of MSI on clinicopathological features and survival of patients affected by Por.<h4>Methods</h4>53 patients affected by Por were investigated. DNA extract ...[more]

PMID: 17557871

Similar Datasets

Project description:BackgroundColorectal (CRC) carcinogenesis through various morphological stages has been linked to several genetic and epigenetic changes. The Raf/MEK/ERK (MAPK) signal transduction cascade is an important mediator of a number of cellular fates.MethodsIn this study, we investigated the presence of B-raf and K-ras mutations in 94 consecutive cases of primary colon adenocarcinoma in correlation with the immunohistochemical expression of total and activated ERK and the expression of mismatch repair proteins (MMR) hMLH1 and hMSH2 as well as their correlations with standard clinicopathological parameters.ResultsThe immunostaining pattern for total and activated ERK was nuclear and cytoplasmic. hMLH1 and hMSH2 proteins were preserved in 45/63 (71.43%) cases and 35/53 (66.04%) cases respectively. Total ERK nuclear expression, was positively correlated with tumor stage (p = 0.049), whereas nuclear pERK expression was positively correlated with histological grade (p = 0.0113) and tumor stage (p = 0.0952), although the latter relationship was of marginal significance. DNA sequencing showed that 12 samples (12.7%) had a mutation in B-RAF Exon 15 and none in Exon 11, whereas 22 (23.4%) had a K-ras mutation. Disruption of the MAP kinase pathway-either through K-ras or B-raf mutation-was detected in 37% of all the examined cases, although the overexpression of total and activated ERK1/2 was not correlated with the mutational status of K-ras or B-raf genes. Finally, the preservation of hMLH1 or hMSH2 immunoexpression was not correlated with the presence of B-raf and/or K-ras mutations.ConclusionsIn this study, we present evidence that ERK activation occurs in a K-ras or B-raf -independent manner in the majority of primary colon cancer cases. Moreover, B-raf mutations are not associated with mismatch-repair deficiency through loss of hMLH1 or hMSH2 expression. Activated ERK could possibly be implicated in tumor invasiveness as well as in the acquisition of a more aggressive phenotype.

Dataset Information

Microsatellite instability in poorly differentiated adenocarcinomas of the colon and rectum: relationship to clinicopathological features.

Publications

Microsatellite instability in poorly differentiated adenocarcinomas of the colon and rectum: relationship to clinicopathological features.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure