Is reduced expression of mismatch repair genes MLH1 and MSH2 in patients with sporadic colorectal cancer related to their prognosis?
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Is reduced expression of mismatch repair genes MLH1 and MSH2 in patients with sporadic colorectal cancer related to their prognosis? / Kruschewski, Martin; Noske, Aurelia; Haier, Jörg; Runkel, Norbert; Anagnostopoulos, Yanis; Buhr, Heinz Johannes.
In: CLIN EXP METASTAS, Vol. 19, No. 1, 2002, p. 71-7.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Is reduced expression of mismatch repair genes MLH1 and MSH2 in patients with sporadic colorectal cancer related to their prognosis?
AU - Kruschewski, Martin
AU - Noske, Aurelia
AU - Haier, Jörg
AU - Runkel, Norbert
AU - Anagnostopoulos, Yanis
AU - Buhr, Heinz Johannes
PY - 2002
Y1 - 2002
N2 - The majority of mutations in hereditary nonpolyposis colon carcinoma (HNPCC) patients affect the mismatch-repair genes (MMRG) MLHI and MSH2. In addition, mutations of these genes were found in about 15% of sporadic colorectal carcinomas which appear to be related to microsatellite instability (MSI). However, mutations in MMRG were not found in all MSI-positive carcinomas, but MMRG mutations may be relevant for the assessment of tumor characteristics and patients' prognosis. Therefore, we investigated the relationship between expression of MMRG, tumor biology and patients' survival. In 127 patients with sporadic colorectal carcinomas and a minimum of 5 years follow-up after curative surgery immunohistochemical detection of MLHI and MSH2 was analyzed semiquantitatively. Lost expression of MLHI has been found in tumor specimens from 10 patients, whereas MSH2 expression was missing in 5 patients. This reduced expression did not correlate with tumor stage, lymph node involvement, grading or tumor invasion into blood vessels. However, a significant correlation was found for lymphovascular invasion (P = 0.02) and localization within the colorectum (P = 0.003) in MLH1-negative carcinomas. In addition, although there was a clear tendency for longer overall survival (72 vs. 63 months) for patients with MLH1-negative carcinomas, significant differences for overall and recurrence-free survival were not seen. In conclusion of our results and a critical review of literature, the prognostic importance of the MMR genes in sporadic colorectal carcinomas remains controversial.
AB - The majority of mutations in hereditary nonpolyposis colon carcinoma (HNPCC) patients affect the mismatch-repair genes (MMRG) MLHI and MSH2. In addition, mutations of these genes were found in about 15% of sporadic colorectal carcinomas which appear to be related to microsatellite instability (MSI). However, mutations in MMRG were not found in all MSI-positive carcinomas, but MMRG mutations may be relevant for the assessment of tumor characteristics and patients' prognosis. Therefore, we investigated the relationship between expression of MMRG, tumor biology and patients' survival. In 127 patients with sporadic colorectal carcinomas and a minimum of 5 years follow-up after curative surgery immunohistochemical detection of MLHI and MSH2 was analyzed semiquantitatively. Lost expression of MLHI has been found in tumor specimens from 10 patients, whereas MSH2 expression was missing in 5 patients. This reduced expression did not correlate with tumor stage, lymph node involvement, grading or tumor invasion into blood vessels. However, a significant correlation was found for lymphovascular invasion (P = 0.02) and localization within the colorectum (P = 0.003) in MLH1-negative carcinomas. In addition, although there was a clear tendency for longer overall survival (72 vs. 63 months) for patients with MLH1-negative carcinomas, significant differences for overall and recurrence-free survival were not seen. In conclusion of our results and a critical review of literature, the prognostic importance of the MMR genes in sporadic colorectal carcinomas remains controversial.
KW - Adaptor Proteins, Signal Transducing
KW - Adenocarcinoma
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Base Pair Mismatch
KW - Carrier Proteins
KW - Colorectal Neoplasms
KW - DNA Mutational Analysis
KW - DNA Repair
KW - DNA, Neoplasm
KW - DNA-Binding Proteins
KW - Disease-Free Survival
KW - Female
KW - Follow-Up Studies
KW - Gene Expression Regulation, Neoplastic
KW - Humans
KW - Life Tables
KW - Male
KW - Middle Aged
KW - MutS Homolog 2 Protein
KW - Neoplasm Proteins
KW - Neoplasm Staging
KW - Nuclear Proteins
KW - Prognosis
KW - Proto-Oncogene Proteins
KW - Survival Analysis
M3 - SCORING: Journal article
C2 - 11918085
VL - 19
SP - 71
EP - 77
JO - CLIN EXP METASTAS
JF - CLIN EXP METASTAS
SN - 0262-0898
IS - 1
ER -