[Molecular Pathology of Colorectal Cancer, Microsatellite Instability - the Detection, the Relationship to the Pathophysiology and Prognosis]. / Molekulární patologie kolorektálního karcinomu, mikrosatelitová nestabilita - zpusob detekce, vztah k patofyziologii a prognóze.

BACKGROUND: Colorectal carcinoma (CRC) is third most common cancer worldwide with very heterogenous character. In most cases, it is caused by sporadic events leading to disruption of epithelial cells of the colon. The minority evolves from germline mutations associated with hereditary cancer syndromes. Mechanisms leading to mutations of oncogenes, tumour suppressors and genes of DNA repair mechanisms include: 1. chromosomal instability, 2. microsatellite instability and 3. CpG island methylator phenotype. Microsatellite instability (MSI) usually arises from a germline mutation of the component of mismatch repair machinery (MMR) or somatic hypermethylation of the MLH1 promoter. The diagnostic approaches include PCR methods and immunohistochemistry for the detection of the loss of MMR part. The aim of our study was to characterise the cohort of ongoing study of gut microbiome in CRC patients considering MSI. MATERIAL AND METHODS: The consecutive study group consisted of 103 patients diagnosed with CRC. The cohort consisted of 45 women (43.7%) and 58 men (56.3%). Patient age at the time of diagnosis was within the range of 31-83 years (median 66 years). The expression of MLH1, MSH2, MSH6 and PMS2 proteins was detected by immunohistochemical method and the positivity was correlated with the stage and the localization of the primary tumour. RESULTS: The MMR status was determined by immunohistochemical method in 43 (41.7%) from the existing total of 103 patients. MSI was detected in 11 (25.6%) cases while 32 (74.4%) were microsatellite stabile. With the respect to cancer clasification the most cases of MSI was detected in stage II (8 cases; 22.2%). In regard to localization of primary tumour, MSI rather correlates to right site CRC, while microsatellite stable tumours do not show any site preferences. CONCLUSION: Considering low number of MMR status determination in study group, statistic evaluation is inaccurate so far. However there is a trend in our cohort in relation to determination of the portion of MSI in CRC population and also in localization of primary tumour according to literature.Key words: colorectal carcinoma - microsatellite instability - Lynch syndrome The work was supported by the project MEYS - NPS I - LO1413 and AZV 16-31966A. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 13. 3. 2017Accepted: 26. 3. 2017.

[Circulating Myeloid Suppressor Cells and Their Role in Tumour Immunology]. / Cirkulující myeloidní supresorové bunky a jejich úloha v nádorové imunologii.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are heterogenic population of multipotent progenitors of myeloid lineage. For their immunosuppressive effect, MDSC are responsible for tumour escape from the host immune surveillance. Furthermore, MDSCs support tumour by promotion of angiogenesis and metastasis. Membrane markers of human MDSCs are myeloid markers CD11b and CD13, these cells are HLA-Drlow/- and expression of CD15 or CD14 differentiate them into granulocytic (Gr-MDSCs) and monocytic (Mo-MDSCs), resp. PATIENTS AND METHODS: Using flow cytometry, we investigated Mo-MDSC counts in peripheral blood of non-cancer individuals - control group (n = 61), breast (n = 39) and colorectal (n = 52) cancer patients. These cells were detected as CD45+CD11b+CD33+CD14+HLA-Drlow/- and quantified as percentage of total white blood cells and as absolute count. RESULTS: In control group, circulating Mo-MDSCs was gender-and age-independent and the average value was 1.09% and 0.073 × 109/l. Breast cancer patients had higher circulating Mo-MDSCs compared to control group with average values: 3.57% and 0.229 × 109/l (p < 0.001) and we also observed increase in Mo-MDSC number after granulopoietic growth factors administration (p = 0.043). Colorectal cancer patients had higher average number of circulating Mo-MDSCs compared to control group: 1.71% a 0.125 × 109/l (p = 0.003) and its number did not correlate with tumour clinicopathological stage, localization of primary tumour (colon vs. rectum), site (left vs. right) and microsatellite instability. CONCLUSION: Increased number of MDSCs in circulation and within tumour microenvironment has been associated with immune suppression and tumour progression. Colorectal cancer patients at diagnosis showed higher circulating Mo-MDSCs possibly reflecting immunosuppressive effect of tumour microenvironment. Change of Mo-MDSC number from baseline level need to be evaluated in the context of CRC patients outcome. Recombinant granulopoietic growth factors increase number of circulating Mo-MDSCs and the effect of this phenomenon on cancer prognosis remains to be elucidated.Key words: myeloid-derived suppressor cells - colorectal cancer - breast cancer - immunology - immunosuppression - G-CSF This work was supported by MEYS by NPU I (LO1413), grant AZV 16-31966A and MH DRO 00209805. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 11. 3. 2017Accepted: 26. 3. 2017.