3 research outputs found
Biomarkers of epithelial-mesenchymal transition in localized, surgically treated clear-cell renal cell carcinoma
Introduction. It has been suggested that the metastatic potential of neoplastic cells can be predicted on the basis of their biological features, including expression of proteins involved in the epithelial to mesenchymal transition (EMT). Therefore, the purpose of this work was to (1) evaluate the expression of EMT markers: ZEB2, vimentin, N-cadherin, TWIST, PTEN, survivin, E-cadherin, Ki-67 and GLUT-1, (2) assess mutation status of two genes: PIK3CA and KRAS, and (3) investigate the potential relationships between the studied biomarkers and clinicopathological factors in clear-cell renal cell carcinoma (ccRCC).Material and methods. Tumor tissue samples (embedded in paraffin blocks) from 159 patients undergoing radical nephrectomy were analyzed. Proteins expression was evaluated immunohistochemically. DNA mutations were analyzed on DNA isolated from tumor tissue and amplified by real-time PCR detection using suitable fluorescent labeled TaqMan assays.Results. One hundred and seven men and 52 women of mean age of 63.1years were enrolled. Fifty four cancers at pTNM stage I–II and 98 at pTNM III–IV stage were diagnosed. There were 30 Fuhrman grade G1, 61 Fuhrman G2, 49 Fuhrman G3 and 19 Fuhrman G4 tumors. A negative correlation between ZEB2 (p = 0.047, r = –0.172) or E-cadherin expression (p = 0.027, r = –0.191) and TNM was observed. Positive association between grade and Ki-67 (p < 0.001), survivin (p < 0.001), vimentin (p < 0.001) immunoreactivity and negative association between TWIST expression (p = 0.029) or PTEN expression (p = 0.013) were found. Ki-67 expression was positively correlated with survivin (p < 0.001, r = 0.617), vimentin (p = 0.001, r = 0.251) and N-cadherin (p = 0,009, r = 0.207) immunoreactivity which can suggest tumor aggressiveness. TWIST was negatively correlated with E-cadherin (p < 0.001, r = –0.284), vimentin (p < 0.001, r = –0.297) and N-cadherin (p < 0.002, r = –0.241). ZEB2 was not associated with ccRCC grade but was negatively correlated with E-cadherin (p = 0.055, r= –0.153) and PTEN (p = 0.006). GLUT-1 expression was inversely linked to E-cadherin expression (p = 0.022, r= –0.182). Mutations in PIK3CA and KRAS genes were not found in any of the studied ccRCC tumors.Conclusions. Low-grade tumors showed higher expression of ZEB2 and TWIST proteins than high-grade tumors, which can suggest that EMT in ccRCC begins at early stages of tumor development and, therefore, evaluation of these proteins, together with other biomarkers, may be useful for assessment of the tumor metastatic potential
Differences in the prognosis of HPV16-positive patients with squamous cell carcinoma of head and neck according to viral load and expression of P16
Purpose To evaluate the impact of HPV16 load (VL-the
number of virus genome copies per cell) and P16 expression
on prognosis of patients with squamous cell carcinomas
(SCCs) of head and neck (HN).
Materials and methods HPV16 presence was assessed in
the group of 109 patients with HNSCCs by quantitative polymerase
chain reaction (qPCR). VL (assessed by qPCR) and
P16 expression (evaluated by immunohistochemistry) were
analysed only in the subgroup of HPV16-positive tumours.
These features were correlated with 5-year overall survival
(OS) and disease-free survival (DFS).
Results HPV16 infection was found in 36 tumours
(33.0%). Virus-positive patients had better OS and DFS
than those without infection (P = 0.041 and 0.005). Among
HPV16-positive HNSCCs, 18 (50.0%) had higher VL
(median value > 6764.3 copies/cell) and 25 (73.5%) P16 over expression. The significant differences in OS and
DFS (P = 0.008 and 0.004) were noticed according to VL,
wherein 100% DFS was found for patients with higher
VL. According to P16 expression, significant difference
was found only for OS (P = 0.020). In multivariate analysis,
VL (P = 0.045; HR = 2.795; CI 0.121-1.060) and the
level of smoking (P = 0.023, HR = 2.253; CI 1.124-4.514)
were independent factors affecting DFS of HPV16-positive
patients.
Conclusion On the basis of viral load, it is possible to
differentiate prognosis of patients with HPV16-positive
HNSCCs. In this subgroup, viral load has stronger prognostic
potential than P16 expression