It has been demonstrated that Notch 1 and Notch 3 proteins may be involved in malignant transformation and development of various types of tumours. The aim of this study was to investigate the role of Notch 1 and 3 proteins as biomarkers of predicting the prognostic outcome for patients with NSCLC Imprint lung cancer specimens were examined from 50 patients with NSCLC who underwent surgical resection. An immunocytochemical method was apply with the use of Notch 1 and Notch 3 antibodies. The expression was correlated with clinicopathological parameters. Overexpression of Notch 1 and Notch 3 proteins was observed in 52% (26/50) and 48% (24/50) of NSCLC. The expression of Notch 1 was significantly correlated with stage (p = 0.02) and grade. The expression of Notch 3 was associated with lymphnode status (p = 0.001) and the stage (p < 0.0001) while the coexpression of Notch 1 and Notch 3 was correlated with lymphnode status (p = 0.0047), stage (p = 0.0001) and grade (p < 0.0001). Coexpression of both proteins had a significantly poorer prognosis than those without coexpression (p < 0.001). In conclusion coexpression of both proteins correlates with poorer prognosis, in patients with resected NSCLC. Furthermore Notch 3 presents as a more attractive prognostic biomarker for NSCLC compared with Notch 1.

Aim: Interleukin – 1 receptor associated kinase 1 (IRAK-1) is increasingly being recognized as an important mediator in cancer initiation and progression. Enhancer of Zeste Homolog 2 (EZH 2) promotes carcinogenesis by epigenetically silencing tumor suppressor genes. We studied IRAK-1 and EZH-2 expression in non-small cell lung carcinoma (NSCLC) and corresponding preneoplastic lesions. Methods: Imprint smears from 102 NSCLC (adenocarcinomas and squamous cell carcinomas) and adjacent atypical squamous metaplasia (n = 20) and normal bronchial epithelium (n = 20) were studied for the immunocytochemical expression of IRAK-1 and EZH2. The results were correlated with patients' clinicopathologic features. Furthermore we investigated the correlation between IRAK-1and EZH-2 expression in tumour imprint specimens. Results: NSCLC tumors demonstrated significantly cytoplasmic and lower nuclear IRAK-1 expression and higher nuclear expression for EZH-2 than normal epithelium. Atypical squamous metaplasia had significantly higher cytoplasmic IRAK-1 and nuclear EZH-2 expression. In tumor specimens; significant positive correlation was detected between IRAK-1 expression and EZH2 (p < 0,0001). The correlation between the expression IRAK-1 and EZH-2 and patients clinicopathologic features varied according to histological type of the tumor and the grade. Conclusions: IRAK-1 and EZH-2 are expressed in high percentages in NSCLC imprint smears and their expression in specimens with atypical squamous metaplasia is an early phenomenon in the sequential development of lung cancer. Disclosure: All authors have declared no conflicts of interest.

Methods: Imprint smears from 102 NSCLC (adenocarcinomas and squamous cell carcinomas) and adjacent atypical squamous metaplasia (n = 20) and normal bronchial epithelium (n = 20) were studied for the immunocytochemical expression of IRAK-1 and EZH2. The results were correlated with patients’ clinicopathologic features. Furthermore we investigated the correlation between IRAK-1and EZH-2 expression in tumour imprint specimens.

Apoptosis induced in primary cultures of rat hepatocytes by transforming growth factor β1(TGF-β1) was greatly attenuated by inhibitors (5 μM) of calpain I and calpain II, respectively. Both inhibitors prevented the TGF-β-elicited increase of nucleosomal DNA fragments and the occurrence of DNA-breaks in the TUNEL reaction. The detrimental effect of TGF-β on cell viability measured by the WST-1 test was strongly reduced by calpain inhibitors. Calpain II > I inhibitors suppressed spontaneous DNA cleavage in hepatocytes during culture and prevented the appearance of immunocytochemically visible TGF-β (APAAP staining), which occurs in untreated parenchymal cell cultures. The data show that inactivation of calpains attenuates both the TGF-β-elicited and the spontaneous apoptosis of cultured hepatocytes; the latter effect is likely due to the suppression of endogenous TGF-β activation. It is suggested that calpains participate in these processes.

Objective: The aim of this study was to investigate expression of the neuropeptides substance P, vasoactive intestinal peptide and heat shock protein 70 in the nasal mucosa cells of patients with seasonal allergic rhinitis, in order to obtain more information on the pathophysiological and immunological role of these markers in allergic rhinitis.Material and methods: Nasal epithelium specimens obtained from 42 patients with allergic rhinitis were studied, using Shandon's Papspin liquid-based cytology method. Smears were immunostained with antibodies against substance P, vasoactive intestinal peptide and heat shock protein 70, and the results were correlated with the clinical features of seasonal allergic rhinitis.Results: A positive reaction for substance P, vasoactive intestinal peptide and heat shock protein 70 was observed in 73.8, 66.7 and 69.0 per cent of the allergic rhinitis mucosal smears, respectively. The Pearson chi-square test showed that 40.5 per cent of the immunostained smears had a positive reaction for one or two of the markers studied (i.e. substance P, vasoactive intestinal peptide or heat shock protein 70), and that 47.6 per cent of the smears had a positive reaction for all the markers (p < 0.0001).Conclusions: We found a high level of expression of substance P and vasoactive intestinal peptide in the nasal mucosa smears of patients suffering from allergic rhinitis. This indicates a role for these neuropeptides in the neuroregulation of immunity and hypersensivity in this disease. Furthermore, expression of heat shock protein 70 may contribute to the development of allergic rhinitis.

Mutations of the PTEN, p53, and beta-catenin genes are the most frequent molecular defects in endometrial carcinomas. The aim of this study was to investigate their prognostic significance in this form of cancer. Imprint smears were obtained from 80 fresh endometrial tumor specimens and studied immunocytochemically for the expression of PTEN, p53, and beta-catenin proteins. The staining pattern was correlated with several well-established prognostic parameters, including 5-year survival. Positive staining of p53 was significantly correlated with increased stage (P < 0.0001), lymph node metastases (P = 0.001), and a nonendometrioid histology (P = 0.001). On the contrary, positive beta-catenin expression was significantly associated with decreased stage (P = 0.002), decreased grade (P = 0.007), and a negative lymph node status (P = 0.023). PTEN positivity was correlated with decreased stage (P = 0.002) and negative lymph nodes (P = 0.008). All the three markers affected survival significantly in univariate analysis but only beta-catenin had an independent prognostic impact. An independent prognostic significance was also shown for PTEN in the stage I subgroup of patients. The results of our study indicate that loss of beta-catenin expression is a strong and independent predictor of an unfavorable outcome in patients with endometrial carcinoma. Loss of PTEN may also be associated with a worse prognosis in patients with early-stage disease.

DEAF-1 is a transcription factor that maps to human chromosomal region 11q15-5 a region that undergoes loss of heterozygozity (LOH) in prostate tumours. The aim of this study was to investigate the expression of DEAF-1 protein in prostate carcinoma cell smears in relationship with clinicopathological parameters.

Hypoxia-inducible factor-1a (HIF-1a) is a transcription factor that plays a major role in contributing to cancer progression. Few reports have identified the existence of single nucleotide polymorphisms in exon 12 of the HIF-1a gene in some carcinomas and in hormone refractory prostate carcinomas. The aim of this study was to investigate the HIF-1a protein expression in the prostates of men with benign hyperplasia (BPH) or carcinomas (Pca) in order to evaluate the malignant potential role of these diseases.

The ability to accurately predict tumor behavior and patient survival is a problem in managing patients with prostate cancer. DNA ploidy provides important information for the evaluation of the prognosis of prostate cancer. The aim of this study was to investigate the DNA ploidy in imprints from prostate adenocarcinomas in a group of 70 patients in relation to Gleason score, tumor differentiation, stage and PSA serum levels. The DNA content was studied in Feulgen-stained imprint smears through the image analysis technique using a SAMBA 2005 Image analyzer. According to our measurements, a strong correlation was observed between DNA ploidy status and tumor differentiation (p<0.001). A statistically significant difference was found between DNA aneuploidy and increased pretreatment PSA serum levels (>4 ng/ml) (p<0.001), as well as between ploidy pattern and stage of the disease (p<0.001). Our results conclude that DNA ploidy status appears to be an additional marker in the field of prognosis of prostatic adenocarcinoma and could provide useful information on the potential behavior of prostate cancer.

The cell proliferation markers p120, Ki-67 and proliferating cell nuclear antigen (PCNA) recognize nuclear antigens. The expression of these proteins by immunostaining methods was reported to be of value in determining the prognosis of patients with malignant diseases.In this study, we evaluated the prognostic significance of the expression of nuclear antigens p120, PCNA and Ki-67 in prostate cancer and compared the results with other prognostic factors.Imprint smear samples obtained from 70 patients immediately after radical prostatectomy for prostatic carcinoma were immunostained with monoclonal antibodies against p120, Ki-67 and PCNA. The immunostaining results were correlated with Gleason score, tumour differentiation, stage and prostatic specific antigen (PSA) levels.Our findings demonstrate that p120, Ki-67 and PCNA expression in prostatic carcinoma smears, correlated significantly with the degree of Gleason score (P < 0.001). When combining p120, Ki-67 and PCNA positivity with tumour differentiation there was a significant association among these parameters (P < 0.001). Overexpression of p120, Ki-67 and PCNA, was also associated with increased PSA serum levels (>4 ng/ml) (P < 0.001). The distribution of p120, Ki-67 and PCNA expression in prostate carcinomas was not statistically significant for Ki-67 (P = 0.69) and p120 (P = 0.22) but was significant for PCNA (P < 0.001) as far as the histological stage (T2a, T2b, T2c, T3a). P120, Ki-67 and PCNA expression had significant prognostic value for disease-free survival.Our results conclude that nuclear antigens p120, Ki-67 and PCNA appear to be additional markers in the field of prognosis of prostatic carcinoma.

WD repeat domain 1 (WDR1), a protein that assists cofilin-mediated actin filament disassembly, is overexpressed in the invading front of invasive ductal carcinoma (IDC), but its implication of overexpression and how to be regulated have not been studied. In our study, we demonstrated that STAT3 bound to the 5′ upstream sequence (− 1971 to − 1964), a putative promoter region, of WDR1 gene, and its activation induced WDR1 overexpression in breast cancer cells. The exogenous overexpression of WDR1 increased the migration of MDA-MB-231, which was attenuated by WDR1 knockdown. In the analysis of breast cancer patients, WDR1 overexpression was associated with a shorter distant metastasis-free survival (DMFS), more specifically in basal-like tumors.

The aim of this study was to investigate by an in situ hybridization procedure the Telomerase expression as a marker in prostate cancer and to correlate these results with several prognostic factors concerning this cancer. Imprint smear samples were obtained from 70 prostates removed from patients who underwent radical prostatectomy for prostate adenocarcinoma. Telomerase expression in cancerous prostate smears was studied using an in situ hybridization procedure. The results were correlated with prognostic factors such as pathologic staging, Gleason grading, PSA serum levels and tumour differentiation. Positive Telomerase expression was detected in 88.6% prostate cancer smears. Telomerase expression was significantly correlated with the Gleason score (p < 0.001), tumour differentiation (p < 0.001) and PSA serum levels (p = 0.002). The distribution of Telomerase expression according to histopathological staging was not statistically significant (p < 0.56). In conclusion Telomerase expression could be a marker indicating the malignant potential of prostate cancer.