Clinical significance of MMR gene aberrant expression
in sporadic colorectal carcinomas.
Émmunohistochemical investigation
Ìeditskou S., Nenopoulou E., Kotoula V., Papadimitriou K.
Dept of Pathology, Medical School, Aristotelian University of
Thessaloniki
Introduction-Aim: The mismatch
repair (MMR) deficiency pathway to malignancy, i.e., aberrant
MMR genes expression giving rise to micrisatellite instability
(MSI), is considered to be implicated in the pathogenesis of a
subset (10-20%) of sporadic colorectal carcinomas and in the majority
(85-90%) of tumors from patients with hereditary nonpolyposis
colorectal cancer syndrome (HNPCC). In this study we examined
the clinical significance of MIR gene aberrant expression in sporadic
colorectal cancer by immunohistochemistry for MSH2 and MLH1 in
correlation with p53 expression, intratumoral microvessel density
(MVD), proliferation activity and clinicopathological features,
with multivariate analysis.
Materials and Methods: Ninety-five sporadic
colorectal carcinomas were evaluated morphologically and immunohistochemically
using anti-p53, Ki67, CD34, MSH2-1, MSH2-2 and MLH1. The minimum
follow up was 5 years. The evaluation of immunohistochemical expression
was performed by using an interactive morphometric program of
image analysis, Prodit 5,2. Statistical analysis was carried out
using the statistic software SPSS.
Results: Lack of expression of both MSH2 and
MLH1, or of either one, was observed in 22% of cases and is observed
in right sided, mucinous, partly mucinous or low differentiated
carcinomas. Loss of mismatch repair gene expression was also found
to correlate with low microvessel density and absence or partial
absence of P53 expression. Dukes classification and the expression
of MLH1, in this study, were independent prognostic factors. P53
overexpression correlated with worse prognosis.
Conclusions: Our results favor the view that
tumors, due to repair deficiency constitute a special group with
different prognosis and distinct clinicopathological and molecular
features. Immunohistochemic examination of mismatch repair genes
can quickly, inexpensively, immediately, distinguish group of
carcinomas arising from MMR deficiency pathway.
Key words: MMR gene proteins, MLH1, MSH2, sporadic colorectal cancers.
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