PECULIARITIES OF DNA REPAIR IN PERIPHERAL BLOOD LYMPHOCYTES AND TUMOR TISSUE OF ENDOMETRIAL CANCER PATIENTS
Keywords:
genome instability, peripheral blood lymphocytes, mismatch-repair, endometrial cancer.Abstract
Summary. Aim: to compare the level of genomic instability in peripheral blood lymphocytes (PBL) and the expression of mismatch-repair (MMR) proteins in endometrial carcinoma cells with clinical characteristics of
endomerial cancer (EC) patients and tumor morphological features. Object and methods: evaluation of MMRproteins MSH2 and MLH1 expression was performed
by immunohistochemical method. DNA repair efficiency
in PBL was assessed by comet assay. Results: according
to immunohistochemical analysis all examined tumors
were divided into MMR-deficient (absence of MSH2
and/or MLH1) and MMR-proficient (presence of both
MSH2 and MLH1). MMR-deficient phenotype was observed mainly in G1- and G2-carcinomas with shallow
myometrial invasion, while MMR-proficient was more
typical for G3-tumors with deep invasion. Median number of recovered DNA damage in PBL was 63.9% and on
this basis all patients were assigned to groups with high
(> 63.9%) and low (< 63.9%) DNA repair efficiency
in PBL. It was shown that in EC patients with DNA repair efficiency in PBL the number of MMR-proficient
carcinomas was 100%, while in patients with low level
it was 78%. In addition, EC patients with high level of
recovered DNA in PBL had stronger MSH2 expression
(label index (LI) 72,0 ± 3,1%) than EC patients with
low level (LI 40,3 ± 2,2%). A similar trend was found
for the MLH1 (LI 66,7 ± 8,6 and 45,6 ± 4,0%, respectively). Conclusion: DNA repair efficiency in PBL
of EC patients is associated with expression of MMRproteins MLH1 and MSH2 that confirms the possibility of using PBL as surrogate markers.
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