Clinical relevance of studies on microsatellite instability and DNA mismatch repair system protein expression in endometrial carcinomas

The evaluation of microsatellite instability in cancer patients might be of clinical importance as a prognostic and predictor factor. The aim of this study − evaluate the frequency and status of microsatellite instability and DNA mismatch repair protein expression in endometrial cancer and to relate the obtained results to clinicopathologic characteristics as well as patient survival. This study enrolled 109 patients.The objectives of the study: to determine the frequency and status of microsatellite instability by using two marker panels (earlier created BAT-25, BAT-26, NR-21, NR-24, MONO-27 and a new BAT-52, BAT-55, BAT-56, BAT-57, BAT-59 panels) recommended by Promega Corporation (USA); to compare the frequency and status of microsatellite instability with tumor clinicopathologic characteristics; to investigate the expression of DNA mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) in tumors with high-frequency microsatellite instability; to evaluate the impact of microsatellite instability on the survival of patients. The results showed that high-frequency microsatellite instability was detected two times more frequently with the new panel of markers in comparison while using earlier created panel. A statistically significant difference regarding tumor grade and myometrial invasion was found between the groups with high-frequency microsatellite instability and stable phenotype. There was no association between the survival of patients and microsatellite instability

Impact of microsatellite instability on survival of endometrial cancer patients

Background and objective: Endometrial cancer (EC) is the most commonly diagnosed gynecologic malignancy among women worldwide and may be classified on the basis of different molecular, pathologic and genetic alterations, including microsatellite instability (MSI). Although MSI is associated with a more favorable outcome in colorectal cancer, its relationship with prognosis in EC cancer is not yet clear. The aim of our study is to identify whether MSI correlates with survival of patients in EC. Materials and methods: We examined MSI status and survival of 109 women. MSI was detected by employing the Promega MSI Analysis System, which used 5 mononucleotides markers (BAT-25, BAT-26, NR-21, NR-24, and MONO-27) to identify MSI in a tumor and normal tissue DNA and 2 pentanucleotide markers (Penta C and Penta D) for specimen identification. Median follow-up of patients was 40.4 months (range 5.2–47.9). Survival was estimated by the Kaplan–Meier method and Cox regression analysis was used to assess the effects of different variables on patient survival. Results: MSI-high was detected in 15.6% EC cases, all of which were associated with endometrioid type histology. Kaplan–Meier survival analysis showed no statistically significant differences between patients with MSI-high and MSI stable tumors (P = 0.4) and multivariate analysis concluded that MSI status remained insignificant after stage, histology and tumor grade adjustment (P = 0.5). Conclusions: Our study showed no statistically significant relationship between MSI-high and survival of endometrial cancer patients

The association between the NOTCH signaling pathway and gynaecological malignancies

Background. The body’s cell behaviour is controlled by various signalling pathways, one of which is NOTCH. It has been found that a partial loss of the NOTCH function or abnormal strengthening of NOTCH signalling are related to various human diseases and developmental disorders. Materials and methods. PubMed was the main source of information for this paper. Results. The paper overviews the association between oncologic diseases and the participants of the NOTCH signalling pathway. In cancerogenesis, the NOTCH signalling pathway can act as a tumour suppressor or an oncogene. The mechanisms of such an effect are yet unknown. The NOTCH signalling pathway is an object of active research because its modulation by pharmacological and genetic approaches could be helpful in discovering new treatment methods of tumours. In this review more attention is paid to gynaecological malignancies, especially to uterine cancer. Conclusions. The findings of recently published studies show that the NOTCH signalling pathway is definitely important for the development of uterine cancer, therefore its components can be potential prognostic biomarkers and molecular therapeutic targets. However, further studies in this field are needed in order to clarify the role of the components of the NOTCH signalling pathway and their interaction with participants of other signalling pathways, which can be important in the development and progression of uterine cancer as well

NOTCH1, NOTCH3, NOTCH4, and JAG2 protein levels in human endometrial cancer

Background and objective: Notch signaling is a conserved developmental pathway, which plays an important role in the regulation of cell proliferation, differentiation and death. Deregulation of Notch pathway has been connected with the carcinogenesis in a variety of cancers. The aim of this study was to investigate the level of the Notch signaling pathway proteins (NOTCH1, 3, 4 and JAG2) in the samples from human endometrial cancer. Materials and methods: The amount of the Notch receptors NOTCH1, 3, 4 and ligand JAG2 protein was determined by Western blot analysis in the samples from stage I endometrial cancer and adjacent nontumor endometrial tissue of 22 patients. Results: The level of NOTCH4 receptor was 1.7 times lower in stage I endometrial cancer as compared with the healthy tissue of the same patients (P = 0.04). The protein level of ligand JAG2 was significantly reduced by 2.5 times in stage IB endometrial adenocarcinoma samples (P = 0.01). It was reduced in the majority of stage IB adenocarcinomas. There were no significant changes in the protein amount of NOTCH1 and NOTCH3 receptors comparing stage I endometrial adenocarcinoma and healthy tissues. Conclusions: The reduced amount of NOTCH4 and JAG2 proteins and the decreased level of mRNA coding Notch proteins, as reported in our previous studies, supports the notion that Notch pathway has rather tumor-suppressive than oncogenic role in human endometrial cancer cells. It suggests that Notch pathway activation is a potential therapeutic target

Mikrosatelitų nestabilumas ir heterozigotiškumo praradimas sergant vėžiu

Straipsnyje pateikiami literatūros duomenys apie mikrosatelitų nestabilumą ir heterozigotiškumo praradimą sergant įvairių lokalizacijų vėžiu. Šie genetiniai pokyčiai yra svarbūs kancerogenezei. Mikrosatelitų nestabilumo ir heterozigotiškumo praradimas gali būti prognoziniu, o kai kuriais atvejais predikciniu žymeniu (rodyti atsaką į gydymą). Daugiausia duomenų yra apie mikrosatelitų nestabilumą sergant storosios žarnos vėžiu. Duomenys apie mikrosatelitų nestabilumą kitų lokalizacijų vėžio atvejais dar kaupiami, taigi, šia tema publikuojamų straipsnių skaičius auga

Integration of human papillomavirus type 16 in cervical cancer cells

Cervical cancer remains an important cause of women morbidity and mortality. The progression of cervical pathology correlates with the HPV integration into the host genome. However, the data on the viral integration status in cervical dysplasias are controversial. The aim of the current study was to evaluate the status of HPV integration in two types of cervical pathology – invasive and non invasive cervical cancer (e.g. carcinoma in situ). 156 women were included in the study: 66 women were diagnosed with invasive cervical cancer (CC) and 90 with non invasive cervical cancer (carcinoma in situ, CIS). 74.2% [95% PI: 63.64÷84.76] of specimens collected from women with diagnosed CC and 85.6% [95% PI: 85.53÷92.85] of CIS specimens were positive for HPV. The most prevalent HPV genotype in both groups was HPV16. To evaluate HPV integration, three selected HPV16 E2 gene fragments were analyzed by PCR. In the majority of CC and CIS specimens the amplification of all three HPV16 E2 gene fragments was observed. The episomal HPV16 form was detected in the majority of CC and CIS specimens. The deletion of all three HPV16 E2 gene fragments was detected in 9.4% of CC specimens and 2.2% of CIS specimens. Finally, integration status could not be used as diagnostical additional test to distinguish between invasive and non invasive cervical cancer

Components of NOTCH signaling for uterine cancer patients' prognosis

New molecular biomarkers that could have an independent prognostic value in endometrial cancer are currently under investigation. Recently, it was suggested that genetic changes in the Notch signaling pathway could be associated with the development of endometrial carcinoma. This study aimed to determine the expression of the Notch signaling pathway components in tumour and adjacent normal uterine tissue and to evaluate their importance for the survival of uterine cancer patients. The present study was performed on uterine body samples collected from 109 patients and paired adjacent noncancerous endometrial tissue samples. Kaplan-Meier curves and Cox regression were used for survival analyses. Expression alterations of NOTCH2, NOTCH3, NOTCH4, JAG2, and HES1 were evaluated as independent and significant prognostic factors for uterine cancer patients

Factors, associated with elevated concentration of soluble carbonic anhydrase IX in plasma of women with cervical dysplasia

Precancerous lesions of human cervix uteri have a tendency for regression or progression. In cervical intraepithelial neoplasia grade 2 (CINII) case there is an uncertainty if a lesion will progress or regress. The carbonic anhydrase IX (CAIX) enzyme is overexpressed in cervical cancer which is more sensitive to radiotherapy. CAIX is associated with poor prognosis in solid hypoxic tumors. The aim of this study was to determine factors related to elevated soluble CAIX (s-CAIX) in high-grade intraepithelial lesion (HSIL) cases. METHODS: Patients diagnosed with HSIL (N = 77) were included into the research group whereas without HSIL (N = 72)-the control group. Concentration of the soluble CAIX (s-CAIX) in plasma was determined by the DIANA ligand-antibody-based method. C. trachomatis was detected from cervical samples by PCR. Primary outcomes were risk factors elevating s-CAIX level in HSIL group. Non-parametric statistical analysis methods were used to calculate correlations. RESULTS: The s-CAIX level in patients with HSIL was elevated among older participants (rs = 0.27, p = 0.04) and with C. trachomatis infection (p = 0.028). Among heavy smokers with HSIL, the concentration of s-CAIX was higher in older women (rs = 0.52, p = 0.005), but was not related to the age of heavy smokers' controls (τ = 0.18 p = 0.40). CONCLUSION: The concentration of s-CAIX was higher among older, heavy smoking and diagnosed with C. trachomatis patients. All these factors increased the risk for HSIL progression