Effect of human papillomavirus on cell cycle-related proteins p16INK4A, p21waf1/cip1, p53 and cyclin D1 in sinonasal inverted papilloma and laryngeal carcinoma. An in situ hybridization study

Human papillomavirus (HPV) infection is implicated as an important risk factor in the development of head and neck cancers. Many studies focusing on the relationships between HPV infection and cell cycle proteins immunoexpression in laryngeal lesions have provided contradictory results. The aim of this study was to evaluate the relationships between HPV DNA presence and p16INK4a, p21waf1/cip1, p53 and cyclin D1 immunoexpression in heterogenous HPV-positive and HPV-negative groups of laryngeal cancers and inverted papillomas. The HPV DNA expression was detected using an in situ hybridization method and immunoexpression of p16INK4a, p21waf1/cip1, p53 and cyclin D1 using immunohistochemistry. The immunoexpression of p21waf1/ /cip1 and p53 proteins was lower in the HPV-positive group compared to the HPV-negative group, although only the difference of p53 staining was statistically significant. The immunoexpression of p16INK4a and cyclin D1 was significantly increased in the HPV-positive group compared to the HPV-negative group. The increased immunoexpression of p16INK4a and cyclin D1, and the lower immunoexpression of p21waf1/cip1 and p53 in the HPV-positive group compared to the HPV-negative group, supports the hypothesis that HPV may play an important role in cell cycle dysregulation. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 34–40

Immunohistochemical study on neuropilin 1 (NRP1) immunoexpression in oral squamous cell carcinoma

  Introduction. Neuropilins (NRPs) are multifunctional glycoproteins that play an important role in angiogenesis and cancer progression. The aim of the study was to examine the immunoexpression of neuropilin 1 (NRP1), the number of NRP1+ infiltrating cells and CD163+ macrophages, and density of microvessels (MVD) in oral squamous cell carcinoma (OSCC). Material and methods. The study was performed on 45 OSCC patients with metastases (OSCCM+), 51 patients without metastases (OSCCM-) and 17 control cases. The microvessels were identified by the presence of CD31 and the expression of the studied proteins was assessed by immunohistochemistry. Results. The immunoexpression of NRP1, the mean numbers of NRP1+, CD163+ infiltrating cells, and MVD were significantly increased in OSCCM+ patients in comparison to OSCCM-, and control groups. Moreover, in OSCCM- patients all these parameters were also significantly increased in comparison to controls. In OSCCM+ and OSCCM- groups, there were positive correlations between the immunoexpression of NRP1 and MVD (r = 0.41, p < 0.006; r = 0.51, p < 0.001, respectively), and between the number of NRP1+ infiltrating cells and CD163+ macrophages (r = 0.56, p < 0.001, r = 0.49, p < 0.001, respectively). Conclusions. The present study revealed overexpression of NRP1 in OSCC, especially in OSCC patients with metasta­sis, suggesting that NRP1 could potentially contribute to metastasis of oral cancer. The correlation between the number of NRP1+ infiltrating cells and CD163+ macrophages suggests that NRP1+ infiltrating macrophages are present in tumor microenvironment and may play a role in the progressions of oral cancer

Immunohistochemical study on survivin in sinonasal tumors and its relationship with the immunoexpression of Ki67 and Bcl-2

 The immunoexpression of the inhibitor of apoptosis protein survivin has been shown to be a significant prognostic factor in various human cancers. Immunohistochemical method was used to examine the expression of survivin, Ki67 and Bcl-2 in 20 cases of sinonasal inverted papillomas (IPs), 12 cases of sinonasal squamous cell carcinoma (SNCs) and 19 cases of nasal chronic sinusitis as a control. Nuclear immunostaining for survivin was observed in 14 of 20 (70%) cases of sinonasal IPs and 10 of 12 (83.4%) cases of SNCs. Apart from nuclear, also weak cytoplasmic immunoexpression of survivin was detected in 2 of 20 cases (10%) of sinonasal IP and moderate intense staining in 9 of 12 cases (75%) of SNC. There was no immunostaining for survivin in 19 control cases. The immunoexpression of survivin, Ki67 and Bcl-2 was significantly higher in SNCs than in sinonasal IPs and control group. Moreover, nuclear survivin and Ki67 antigen immunoexpression were significantly higher in sinonasal IPs group as compared to control group. There were statistically significant positive correlations between nuclear (but not cytoplasmic) immunoexpression of survivin and Ki67 antigen, as well as Bcl-2 oncoprotein in both tested tumors. In conclusion, our findings suggest that survivin, Ki67 and Bcl-2 may be involved in sinonasal tumorigenesis.

Effect of human papillomavirus on cell cycle-related proteins p16INK4A, p21waf1/cip1, p53 and cyclin D1 in sinonasal inverted papilloma and laryngeal carcinoma. An <i>in situ</i> hybridization study

Human papillomavirus (HPV) infection is implicated as an important risk factor in the development of head and neck cancers. Many studies focusing on the relationships between HPV infection and cell cycle proteins immunoexpression in laryngeal lesions have provided contradictory results. The aim of this study was to evaluate the relationships between HPV DNA presence and p16INK4a, p21waf1/cip1, p53 and cyclin D1 immunoexpression in heterogenous HPV-positive and HPV-negative groups of laryngeal cancers and inverted papillomas. The HPV DNA expression was detected using an in situ hybridization method and immunoexpression of p16INK4a, p21waf1/cip1, p53 and cyclin D1 using immunohistochemistry. The immunoexpression of p21waf1/ /cip1 and p53 proteins was lower in the HPV-positive group compared to the HPV-negative group, although only the difference of p53 staining was statistically significant. The immunoexpression of p16INK4a and cyclin D1 was significantly increased in the HPV-positive group compared to the HPV-negative group. The increased immunoexpression of p16INK4a and cyclin D1, and the lower immunoexpression of p21waf1/cip1 and p53 in the HPV-positive group compared to the HPV-negative group, supports the hypothesis that HPV may play an important role in cell cycle dysregulation. <i>(Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 34–40

Distinct inhibitory efficiency of siRNAs and DNAzymes to β1 integrin subunit in blocking tumor growth

Receptors of the β1 integrin family are involved in many tumor-promoting activities. There are several approaches currently used to control integrin activity, and thus to potentially restrain tumor metastasis and angiogenesis. In this study, we compared inhibitory efficiencies of siRNA and DNAzymes against the β1 integrin subunit (DEβ1), in a mouse xenograft model. Both inhibitors were used under their most favorable conditions, in terms of concentrations, incubation time and lack of cytotoxic effects. Transfection of siRNAβ1 or DEβ1 remarkably inhibited the growth of both PC3 and HT29 colon cancer cells in vitro, and decreased their capability of initiating tumor formation in the mouse xenograft model. siRNAβ1 appeared to be slightly more efficient than DEβ1 when tested in vitro, however it was comparably less proficient in blocking the tumor growth in vivo. We conclude the DNAzyme, due to its greater resistance to degradation in extra- and intracellular compartments, to be a superior inhibitor of tumor growth in long lasting experiments in vivo when compared to siRNA, while the latter seems to be more efficient in blocking β1 expression during in vitro experiments using cell cultures

E-cadherin expression is more associated with histopathological type of thyroid cancer than with the metastatic potential of tumors

The aim of this study was to evaluate the relationship between abnormal expression of E-cadherin(E-CAD) and the extracapsular extension of tumors, lymph node involvement and the presence of metastasis invarious types of thyroid cancers. Histopathological specimens of 35 benign thyroid lesions and 122 malignanttumors (papillary, follicular, poorly differentiated and undifferentiated cancers) were analyzed. E-CAD immunostainingintensity, its subcellular localization, homogeneity within lesion, and the relation of staining intensitybetween tumor and surrounding thyroid parenchyma were evaluated. The obtained results show that the variantsof differentiated cancers with a poorer prognosis (i.e. tall cell and follicular variants of papillary cancer andwidely invasive follicular cancers) present reduced intensity of E-CAD expression, its abnormal localization orheterogeneity of staining more frequently than classical papillary cancers and minimally invasive follicular cancers.However, the assessment of E-CAD expression does not allow the prediction of extrathyroidal growth ofthyroid cancers