High Wilms' tumour gene (WT1) expression and low mitotic count are independent predictors of survival in diffuse peritoneal mesothelioma.

AIMS: To evaluate the use of the Wilms' tumour gene (WT1) marker and histomorphological parameters as indicators of prognosis in malignant peritoneal mesothelioma (MPM). METHODS AND RESULTS: Histological samples of 31 MPM were stained immunohistochemically for the WT1 protein. The results were quantified by recording the number of stained nuclei, and then correlated with patient survival. Statistical correlation was evaluated for tumour histotype, mitotic count (MC), nuclear grade (NG), necrosis, lymphoid response (grade of inflammation) and desmoplasia with regard to survival. High-grade histology (solid epithelioid, pure sarcomatoid or biphasic tumours), high NG, MC more than five per 10 per high-power field (HPF), necrosis and desmoplasia were associated with a significantly worse prognosis. Patients with MPM with low WT1 expression (≤25% of positive cells) survived for a significantly shorter time compared to those with high WT1 expression (>25% of positive cells) (P = 0.0001). The 50% survival time of subjects with low WT1 expression was 2.9 months [95% confidence interval (CI): 2.05-3.71] versus 31.5 months (95% CI: 20.4-42.5) for those with high WT1 expression. On multivariate analysis, WT1 and MC were found to be associated independently with survival (P = 0.002; P = 0.005, respectively). CONCLUSIONS: Our study suggests that low WT1 expression and high MC may be indicative of an unfavourable prognosis in patients with advanced malignant peritoneal mesothelioma.

Giant angioleiomyoma of uterus: A case report with focus on CT imaging.

We report a rare case of giant angioleiomyoma located in the uterus and detected in a 37-year-old woman. The uterus is an extremely rare location for angioleiomyoma. The definitive diagnosis is usually obtained only after the histopathologic examination because the imaging criteria are challenging for this disease. We focused our attention on the main computed tomography features able to provide a robust preoperative diagnosis of this rare clinical entity.

The role of survivin in thyroid tumors: differences of expression in well-differentiated, non-well-differentiated, and anaplastic thyroid cancers.

BACKGROUND: Survivin is involved in human cancer and is responsible for aggressive biological behavior and poor clinical outcomes in several human malignancies. Thus, we hypothesized that the upregulation of survivin protein expression may be enhanced in parallel with transition toward a poorly differentiated phenotype in human thyroid carcinomas. METHODS: The expression of survivin was evaluated, using a standard linked streptavidin-biotin horseradish peroxidase technique technique, in a series of 56 human thyroid carcinomas (42 papillary, 4 poorly differentiated, and 10 anaplastic carcinomas) and thyroid carcinoma cell lines at different degrees of differentiation. RESULTS: The cytoplasmic expression of survivin protein was significantly upregulated in all thyroid tumors. A statistically significant association was found between nuclear survivin expression and anaplastic thyroid cancer (mean ± SD: well-differentiated thyroid cancer, 1.22 ± 20.21; non-well-differentiated thyroid cancer, 34.00 ± 25.17; anaplastic thyroid cancer, 56.50 ± 22.10; p<0.001). Nuclear staining of survivin has been shown in poorly differentiated and anaplastic thyroid carcinomas, and this is likely due to the upregulation of the ΔEx3 survivin splicing variant, as shown in poorly differentiated/anaplastic thyroid carcinoma cell lines. Of note, selected thyroid tumors characterized by a mixed population of differentiated and undifferentiated neoplastic cells, likely progressing from well to poorly differentiated and anaplastic phenotypes, exhibited cytoplasmic expression of survivin in differentiated fields and nuclear protein staining in poorly differentiated and anaplastic areas. This expression profile provides substantial added value to conventional clinical markers in predicting anaplastic cancer. The cut-off for distinguishing thyroids that developed ATC from those that remained differentiated was >30% of nuclear survivin expression. The receiver operating characteristic (ROC) area was 0.92, with a p-value of <0.0001. CONCLUSIONS: Upregulation of survivin expression may be a molecular marker of dedifferentiation in thyroid epithelial carcinomas, likely being responsible for survival responses of tumor cells and, thus, favoring progression toward a poorly differentiated phenotype.

Beta-catenin and epithelial tumors: a study based on 374 oropharyngeal cancers.

INTRODUCTION: Although altered regulation of the Wnt pathway via beta-catenin is a frequent event in several human cancers, its potential implications in oral/oropharyngeal squamous cell carcinomas (OSCC/OPSCC) are largely unexplored. Work purpose was to define association between beta-catenin expression and clinical-pathological parameters in 374 OSCCs/OP-SCCs by immunohistochemistry (IHC). MATERIALS AND METHODS: Association between IHC detected patterns of protein expression and clinical-pathological parameters was assessed by statistical analysis and survival rates by Kaplan-Meier curves. Beta-catenin expression was also investigated in OSCC cell lines by Real-Time PCR. An additional analysis of the DNA content was performed on 22 representative OSCCs/OPSCCs by DNA-image-cytometric analysis. RESULTS AND DISCUSSION: All carcinomas exhibited significant alterations of beta-catenin expression (P < 0.05). Beta-catenin protein was mainly detected in the cytoplasm of cancerous cells and only focal nuclear positivity was observed. Higher cytoplasmic expression correlated significantly with poor histological differentiation, advanced stage, and worst patient outcome (P < 0.05). By Real-Time PCR significant increase of beta-catenin mRNA was detected in OSCC cell lines and in 45% of surgical specimens. DNA ploidy study demonstrated high levels of aneuploidy in beta-catenin overexpressing carcinomas. CONCLUSIONS: This is the largest study reporting significant association between beta-catenin expression and clinical-pathological factors in patients with OSCCs/OPSCCs.

pEGFR-Tyr 845 expression as prognostic factors in oral squamous cell carcinoma: a tissue-microarray study with clinic-pathological correlations.

The EGFR (epidermal growth factor receptor) a member of the family of transmembrane protein kinase receptors known as the erbB family shows a significant correlation with the presence of metastases and poorly differentiated oral cancer. Aim of the present work is to define the key-role of EGFR in oral cancer prognosis. We have analyzed the EGFR expression on 149 cases of oral squamous cell cancers (OSCC) and we have found that it was poorly expressed in normal oral epithelium, but its expression was significantly increased in OSCCs. Moreover, we have recorded that both pEGFR-Tyr 845 and pEGFR-Tyr 1068 were mainly distributed in high histological grading and in advanced stages. Western blotting has confirmed the total absence of EGFR phosphorylation in normal oral epithelium and the higher level of protein phosphorylation in representative cases of OSCCs. The EGF-R amplification was found by fluorescence in situ hybridization (FISH) in 14% of OSCC; interestingly, EGF-R amplification was mainly observed in OSCC with higher histological grading (G2 and G3) and advanced stage (pT4) sub-groups. Kaplan-Meyer survival analysis suggested that patients with positive pEGFR-Tyr 845 tumors had a worse prognosis and were bad responders to chemotherapy. These results confirm the central role of EGF-R activation status as a prognostic biomarker in OSCC.