Cancer stem cell marker expression and methylation status in patients with colorectal cancer.

The number of individuals diagnosed with colorectal cancer (CRC) has been on an alarming upward trajectory over the past decade. In some countries, this cancer represents one of the most frequently diagnosed types of neoplasia. Therefore, it is an important demand to study the pathology underlying this disease to gain insights into the mechanism of resistance to treatment. Resistance of tumors to chemotherapy and tumor aggressiveness have been associated with a minor population of neoplastic cells, which are considered to be responsible for tumor recurrence. These types of neoplastic cells are known as cancer stem cells, which have been previously reported to serve an important role in pathogenesis of this malignant disease. Slovakia has one of the highest incidence rates of CRC worldwide. In the present study, the aim was to classify the abundance of selected stem cell markers (CD133, CD166 and Lgr5) in CRC tumors using flow cytometry. In addition, the methylation status of selected genomic regions of CRC biomarkers (ADAMTS16, MGMT, PROM1 (CD133), LGR5 and ALCAM) was investigated by pyrosequencing in a cohort of patients from Martin University Hospital, Martin, Slovakia. Samples from both primary tumors and metastatic tumors were tested. Analysis of DNA methylation in the genomic regions of indicated five CRC biomarkers was also performed, which revealed the highest levels of methylation in the A disintegrin and metalloproteinase with thrombospondin motifs 16 and O6-methyguanine-DNA methyl transferase genes, whereas the lowest levels of methylation were found in genes expressing prominin-1, leucine-rich repeat-containing G-protein-coupled receptor 5 and activated leukocyte cell adhesion molecule. Furthermore, tumor tissues from metastases showed significantly higher levels of CD133+ cells compared with that in primary tumors. Higher levels of CD133+ cells correlated with TNM stage and the invasiveness of CRC into the lymphatic system. Although relatively small number of samples was processed, CD133 marker was consider to be important marker in pathology of CRC.

Genomic profile and immune contexture in colorectal cancer-relevance for prognosis and immunotherapy.

Colorectal cancer (CRC) is one of the leading cancers in both genders. TNM staging system is still the most commonly used tumor classification and prognostic system. The disadvantage of TNM is that the prognostic information it provides is incomplete, and patients with the same histological tumor stages may differ significantly in the clinical outcome. Therefore, the identification of new prognostic parameters is crucial. The carcinogenic process that gives rise to an individual tumor is unique and tumor microenviroment should be taken into consideration. In CRC, T-cell infiltration is not homogenous, and recent studies are mostly focusing on memory T-cells and CD8 cells in predicting disease-free survival (DFS) and overall survival (OS). It seems that DFS and OS are not only dependent on microsatellite instable or stable status but mostly on the levels of expression of the immune signatures. Also, patients with high infiltration of cytotoxic and memory cells have significantly better outcome. This review consolidates current knowledge and recent research about importance of immune-cell-associated proteins, specific gene profiles of immune cells and immunotherapy in CRC. We also discussed cell-specific signatures in cancer treatment.

miRNA Expression Profiles in Luminal A Breast Cancer-Implications in Biology, Prognosis, and Prediction of Response to Hormonal Treatment.

Breast cancer, which is the most common malignancy in women, does not form a uniform nosological unit but represents a group of malignant diseases with specific clinical, histopathological, and molecular characteristics. The increasing knowledge of the complex pathophysiological web of processes connected with breast cancercarcinogenesis allows the development of predictive and prognostic gene expressionand molecular classification systems with improved risk assessment, which could be used for individualized treatment. In our review article, we present the up-to-date knowledge about the role of miRNAs and their prognostic and predictive value in luminal A breast cancer. Indeed, an altered expression profile of miRNAs can distinguish not only between cancer and healthy samples, but they can classify specific molecular subtypes of breast cancer including HER2, Luminal A, Luminal B, and TNBC. Early identification and classification of breast cancer subtypes using miRNA expression profilescharacterize a promising approach in the field of personalized medicine. A detection of sensitive and specific biomarkers to distinguish between healthy and early breast cancer patients can be achieved by an evaluation of the different expression of several miRNAs. Consequently, miRNAs represent a potential as good diagnostic, prognostic, predictive, and therapeutic biomarkers for patients with luminal A in the early stage of BC.

Genetic and epigenetic analysis of the beta-2-microglobulin gene in microsatellite instable colorectal cancer.

One of the most common mechanisms of immune evasion in MSI colorectal cancers (CRCs) is loss of HLA class I expression due to mutations in B2M gene which can become a negative predictor for checkpoint blockade therapy. The aim of this study was the determination of prevalence of B2M somatic mutations in MSI CRC patients and relationship between B2M mutations and lymphocytes infiltration and other clinicopathological features as well as detection of methylation changes in B2M promoter region which can be another mechanism of immune escape. In our study, 37 MSI-H and 5 MSI-L patients were selected for screening of B2M mutational and methylation status. The characterization of patients was based on standard histopathological diagnosis and TNM classification; BRAF, KRAS mutations, tumor-infiltrating lymphocytes and peritumoral lymphoid reaction were also determined. MSI analysis was performed using fragment analysis. B2M mutations were identified by Sanger sequencing, and methylation of CpG islands in promoter region was detected by methylation-specific PCR. Heterozygous mutations in the B2M gene were detected in five MSI-H patients (13.5%), while the mutation c.45_48delTTCT was determined in four patients and mutation c.276delC was found in two patients. One of these five patients was compound heterozygote harboring both mutations. Methylation of the promoter region of the B2M gene was observed in one patient with MSI-H colorectal cancer. Detection of genetic and epigenetic changes in B2M gene could be important in personalized therapy for CRC patients as these changes may be one of the mechanisms of secondary resistance of MSI positive tumors to immunotherapy.

Breast Cancer in Young Women: Status Quo and Advanced Disease Management by a Predictive, Preventive, and Personalized Approach.

Why does healthcare of breast cancer (BC) patients, especially in a young population, matter and why are innovative strategies by predictive, preventive, and personalized medicine (PPPM) strongly recommended to replace current reactive medical approach in BC management? Permanent increase in annual numbers of new BC cases with particularly quick growth of premenopausal BC patients, an absence of clearly described risk factors for those patients, as well as established screening tools and programs represent important reasons to focus on BC in young women. Moreover, "young" BC cases are frequently "asymptomatic", difficult to diagnose, and to treat effectively on time. The objective of this article is to update the knowledge on BC in young females, its unique molecular signature, newest concepts in diagnostics and therapy, and to highlight the concepts of predictive, preventive, and personalized medicine with a well-acknowledged potential to advance the overall disease management.

Mullerian adenosarcomas of the uterine cervix with sarcomatous overgrowth.

Mullerian adenosarcoma with sarcomatous overgrowth (MASO) of the uterine cervix is an extremely rare variant of adenosarcoma of the genital tract associated with aggressive clinical course. We searched the PubMed and Medline databases for MASO of the cervix and we identified and reviewed eleven cases published between years 2004 and 2017. The most common clinical picture includes abnormal vaginal bleeding, postcoital bleeding, pelvic pain and foul-smelling vaginal discharge. Therapeutic options for MASO are still undefined. Radical hysterectomy with sufficient tumour-free margins combined with adjuvant chemotherapy and radiotherapy should serve as an effective treatment tool with favourable outcome.