Triple negative phenomenon in endometrial cancer: recognition criteria and impact on survival

Objectives: Endometrial cancer is the most common malignant cancer of female reproductive organs. The number of diagnosed cases of endometrial cancer is increasing from year to year. Endometrial cancer is a neoplasm with a good survival rate. However, there are also cases with a fast, aggressive course. In recent years, the triple negative phenomenon (TNP) has been identified as one of the factors determining shorter survival in patients with endometrial cancer. Material and methods: The study covered 265 patients with histopathologically confirmed endometrial cancer. Patients were divided into two groups: 1) patients with endometrial cancer with TNP; 2) patients with endometrial cancer without TNP. Tissue microarrays (TMA) were examined with immunohistochemistry to evaluate the expression of estrogen, progesterone and HER2 receptors. In several cases FISH method was used to assess HER2. The expression was evaluated by computer image analysis using the Nuclear Image Analysis virtual microscopy system. The evaluation of HER2 expression was performed manually. The criterion for TNC diagnosis was H-Score < 50 or < 75 and Allred score < 4. Results: Depending on the scoring system used, TNP was found in from 10.19% to 15.09% of cases. Regardless of the criteria employed in endometrial cancer, the presence of TNP was neither a factor increasing the risk of death nor it affected the patients' survival. Conclusions: The proportion of TNP diagnosed in endometrial cancer depends on the examined population and the diagnostic criteria. The incidence of TNP did not affect the survival of patients

Nucleolin and nucleophosmin expression in seminomas and non-seminomatous testicular tumors

Introduction. Testicular tumors are heterogeneous group of neoplasms divided mainly into two types: seminomas and non-seminomas. Nucleolin (NCL) and nucleophosmin (NPM) are abundant nucleolar proteins involved in many physiologic and pathologic processes including cancer. Their overexpression was found in many tumors but it was not studied in testicular cancer. Material and methods. The study was performed on tissue microarrays of 19 seminomas, 21 embryonal carcinomas and 11 yolk sac tumors. The expression of NCL and NPM was detected with monoclonal antibodies and visualized with EnVision FLEX/HRP technique. Immunohistochemical reactions were measured with Aperio ImageScope Software and analyzed as means of percentages of all immunopositive cells in three groups of reaction intensity, i.e. 3+, 2+, and 1+ as well as of H-score. Results. Seminomas showed higher expression of nucleolin indicated by higher H-score and higher percentage of positive cells than non-seminomas. The differences in subpopulations of NCL-positive cells were also found. Embryonal carcinomas and yolk sac tumors showed lower expression of NCL than seminomas indicated by H-score. The percentage of NCL-positive cells did not differ between embryonal carcinomas and seminomas while there were significant differences in subpopulations of cells. The percentage of NCL-positive cells in yolk sac tumors was lower than in seminomas. The results show different heterogeneity of subpopulations of NCL-positive cells in embryonal carcinomas and yolk sac tumors compared to seminomas. The analysis of nucleolin expression in embryonal carcinomas and yolk sac tumors showed no differences between these two tumor types. No differences in nucleophosmin expression between seminomas and non-seminomas were found. Conclusions. The differences in the expression of nucleolin between two groups of germ cell testicular tumors found in the current study indicate a new aspect of biology of these neoplasms and require further studies on the role of nucleolin in germ cell tumorigenesis

Expression of p21WAF1 in Astler–Coller stage B2 colorectal cancer is associated with survival benefit from 5FU-based adjuvant chemotherapy

In several, but not all, previous studies, positive p21WAF1 expression has been suggested as an indicator of a good prognosis in patients with stage III/IV colorectal cancer. However, it is not known whether the same is true for stage B2 patients. The purpose of this study is to assess the influence of p21WAF1 expression in tumor cells on disease-free survival (DFS) and overall survival (OS) of Astler–Coller stage B2 and C patients with colorectal cancer who underwent 5-fluorouracil-based adjuvant chemotherapy. Nuclear p21WAF1 was detected by immunohistochemistry in tissue microarrays from 275 colorectal cancers. The expression of p21WAF1 was associated with DFS (p = 0.025) and OS (p = 0.008) in the subgroup of stage B2 patients that was treated with adjuvant chemotherapy. In multivariate analysis, it remained the only independent prognostic parameter in relation to DFS and OS (p = 0.035 and p = 0.02, respectively). In the subgroup of 72 stage B2 patients with positive p21WAF1 expression but not in the subgroup of 61 stage B2 patients with negative p21WAF1 expression, adjuvant chemotherapy was associated with better DFS (85% 5-year survival versus 65% without chemotherapy, p = 0.03) and OS (96% versus 82%, p = 0.014). In the combined stage B2 and C group of patients treated with adjuvant chemotherapy, positive p21WAF1 expression was also associated with better DFS and OS (p = 0.03, p = 0.002, respectively). Expression of p21WAF1 in colorectal tumor cells identifies a subgroup of Astler–Coller stage B2 patients who could benefit significantly from 5FU-based chemotherapy and may improve the selection of patients for adjuvant chemotherapy

Liver Expression of Sulphotransferase 2A1 Enzyme Is Impaired in Patients with Primary Sclerosing Cholangitis: Lack of the Response to Enhanced Expression of PXR

Background/Aim. Sulphotransferase 2A1 (SULT2A1) exerts hepatoprotective effects. Transcription of SULT2A1 gene is induced by pregnane-X-receptor (PXR) and can be repressed by miR-378a-5p. We studied the PXR/SULT2A1 axis in chronic cholestatic conditions: primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC). Materials/Methods. Western-blot/PCRs for SULT2A1/PXR were performed in PSC (n=11), PBC (n=19), and control liver tissues (n=19). PXR and SULT2A1 mRNA was analyzed in intestinal tissues from 22 PSC patients. Genomic DNA was isolated from blood of PSC patients (n=120) and an equal number of healthy volunteers. Liver miRNA expression was evaluated using Affymetrix-Gene-Chip miRNA4.0. Results. Increased PXR protein was observed in both PSC and PBC compared to controls and was accompanied by a significant increase of SULT2A1 in PBC but not in PSC. Decreased expression of SULT2A1 mRNA was also seen in ileum of patients with PSC. Unlike PBC, miRNA analysis in PSC has shown a substantial increase in liver miR-378a-5p. Conclusions. PSC is characterized by disease-specific impairment of SULT2A1 expression following PXR activation, a phenomenon which is not noted in PBC, and may account for the impaired hepatoprotection in PSC. miRNA analysis suggests that SULT2A1 expression in PSC may be regulated by miR-378a-5p, connoting its pathogenic role