ABSTRACT
Microsatellite-unstable genotype associated with deficiency mismach repaired enzymes leads to the accumulation of a series of mutations in the coding and regulatory regions of the genes having a role in carcinogenesis in endometrial cancer (ECs). The aim of this study was to investigate the correlation between the expression of four main mismach repaired enzyme (MLH-1, MSH-2, MSH-6 and PMS-2) with patients survival. ECs from 70 women (median of 63 years, range of 43-79 years) were assessed immunohistochemically for microsatellite instability (MSI). In our study we found that the presence of MSI, determined by the absence of immunohistochemically expression of at least one of the test four of the enzyme mismach repaired system is associated, not statistically significant, with longer survival (p = 0.558). In conclusion we may state that the immunohistochemical analysis who indicates MSI in biopsy tissue is a one step forward for the determination of survival and progression of endometrial carcinoma.
Subject(s)
Endometrial Neoplasms/genetics , Microsatellite Instability , Adult , Aged , DNA Mismatch Repair , DNA-Binding Proteins/analysis , DNA-Binding Proteins/genetics , Endometrial Neoplasms/epidemiology , Endometrial Neoplasms/pathology , Endometrium/metabolism , Endometrium/pathology , Female , Genotype , Humans , Immunohistochemistry , Middle Aged , Mismatch Repair Endonuclease PMS2/analysis , Mismatch Repair Endonuclease PMS2/genetics , MutL Protein Homolog 1/analysis , MutL Protein Homolog 1/genetics , MutS Homolog 2 Protein/analysis , MutS Homolog 2 Protein/genetics , Survival AnalysisABSTRACT
In recent years, increasing attention has been paid to the rate of spread of endometrial carcinoma, especially in the postmenopausal period. Along with routine diagnostic methods, giving information on the location and progression of the disease, there are some morphological methods determining very accurately the correlations in the development of this type of cancer and his prognosis. Moreover--in recent years, the accumulated information about the molecular profile of this type of cancer made it possible to implement a number of new drugs against the so-called molecular therapy -'targets' in the neoplastic process. Significant proportion of cases show response rates, it is more hope in the development of more successful formulas and target -based therapy. In this review, we present and discuss the role of certain molecular markers as potential indicators of prognosis and development, as well as determining the target treatment of endometrial carcinoma.
Subject(s)
Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/drug therapy , Endometrium/pathology , Molecular Targeted Therapy , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Endometrial Neoplasms/genetics , Endometrial Neoplasms/metabolism , Endometrium/metabolism , ErbB Receptors/genetics , ErbB Receptors/metabolism , Female , Humans , PTEN Phosphohydrolase/genetics , PTEN Phosphohydrolase/metabolism , Prognosis , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Microsatellite instability (MSI) is involved in the pathogenesis of about 30% of endometrial cancer cases. In accumulating data from the past few years MSI is shown to have both clinical and prognostic value. In the present work we are discussing the components and molecular mechanisms of functioning of the mismatch repair system (MMR). MSI is a hallmark of endometrial tumors with DNA MMR deficiency. We summarized the main pathways for accumulating mutations in coding and non-coding DNA sequences, which is a result of errors during replication of microsatellite tandem repeats. A few studies rising valuable conclusions about the correlation between MSI and endometrial cancer are revised.
