EGFR, HER-2 and COX-2 levels in colorectal cancer

Aims: Receptor tyrosine kinases epidermal growth factor receptor (EGFR) and HER-2 and cyclooxygenase-2 (COX-2) are promising molecular targets for cancer therapy and/or prevention. The aim was to evaluate EGFR, HER-2 and COX-2 mRNA and protein expression in colorectal cancer patients. Methods and results: EGFR, HER-2 and COX-2 protein levels were evaluated by immunohistochemistry in malignant tissue, dysplastic tissue and normal mucosa samples from 124 cases with primary colorectal carcinoma. Moreover, the corresponding mRNA levels were assessed by quantitative reverse transcriptase-polymerase chain reaction in 46 colorectal carcinomas. There was strong correlation between mRNA and protein expression for EGFR (P < 0.001), HER-2 (P < 0.004) and COX-2 (P < 0.007). EGFR levels did not correlate with stage of the disease or tumour differentiation. HER-2 and COX-2 levels increased in advanced stages and in differentiated carcinomas. Furthermore, a correlation between HER-2 and COX-2 expression was revealed in neoplastic tissue. Conclusions: EGFR as well as HER-2 and COX-2 overexpression represent important alterations that are related to the molecular pathways underpinning colorectal carcinogenesis. Further investigation is required to evaluate the impact of these markers on the management of patients with colorectal cancer. © 2008 The Authors

Prion protein expression and the M129V polymorphism of the PRNP gene in patients with colorectal cancer

The prion protein, PrPC, is known mostly for its involvement in neurodegenerative spongiform encephalopathies. However, a role for this molecule in cancer is becoming increasingly recognized partly because it promotes cell proliferation and inhibits apoptosis. Moreover, the codon 129 polymorphism (M129V) of the PRNP gene (the PrPC-encoding gene) has been associated with neurodegenerative disease development and severity, while no information is available regarding its role in colorectal cancer (CRC) incidence and disease progression. We have previously reported that expression levels of PRNP may have a prognostic value in CRC, suggesting a role for the prion protein in CRC. The aim of this study was to investigate retrospectively the possible role of M129V and PrPC expression in patients with CRC. The M129V single nucleotide polymorphism was genotyped by real time polymerase chain reactions in 110 patients with CRC and 124 healthy donors. Moreover, protein expression was assessed by immunohistochemistry in 68 patients with CRC. Allele frequencies were similar in patients and healthy controls indicating that the M129V polymorphism is not a risk factor for CRC. Furthermore, it did not correlate with any clinicopathological parameters. By contrast, PrPC expression was highly elevated in neoplastic compared to normal tissue and differed depending on the primary site. Interestingly, protein levels were correlated with disease recurrence (P = 0.007). Conclusively, PrPC overexpression may constitute a prognostic marker for disease recurrence and potentially a new target for anticancer therapy. However, further studies are needed to evaluate prospectively the role of PrPC expression in patients with CRC. © 2010 Wiley-Liss, Inc

Evaluation of the prognostic and predictive value of p53 and Bcl-2 in breast cancer patients participating in a randomized study with dose-dense sequential adjuvant chemotherapy

Purpose: To assess the prognostic and predictive significance of p53 and Bcl-2 protein expression in high risk patients with breast cancer treated with dose-dense sequential chemotherapy. Patients and methods: From June 1997 until November 2000, 595 patients were randomized to three cycles of epirubicin (E) 110 mg/m 2 followed by three cycles of paclitaxel (P) 250 mg/m 2 followed by three cycles of 'intensified' CMF (cyclophosphamide 840 mg/m 2, methotrexate 47 mg/m 2 and fluorouracil 840 mg/m 2) or to four cycles of E, followed by four cycles of CMF. p53 and Bcl-2 expression was investigated by immunohistochemistry in 392 and 397 patients respectively. Results: Positive expression of p53 was detected in 104 (26.5%) patients and was significantly associated with negative hormonal status, worse histologic grade, higher incidence of disease relapse and higher rate of death. p53 positive expression was a significant negative predictor of overall survival (OS) (P = 0.002) and disease-free survival (DFS) (P = 0.001). Negative expression of Bcl-2 was detected in 203 (51%) patients and was significantly associated with negative hormonal status. Multivariate analysis revealed that, positive p53 expression, higher number of positive nodes and worse tumor grade were related to significantly poorer OS and DFS. Conclusions: For both treatments, p53 positive expression was a significant negative prognostic factor for OS and DFS while Bcl-2 was not. No predictive ability of p53 status or Bcl-2 status for paclitaxel treatment was evident. © 2006 Oxford University Press

Evaluation of the prognostic value of HER-2 and VEGF in breast cancer patients participating in a randomized study with dose-dense sequential adjuvant chemotherapy

Purpose. To assess the prognostic and predictive significance of HER-2 overexpression and high expression of VEGF in high-risk patients with breast cancer treated with dose-dense sequential chemotherapy. Patients and methods. From June 1997 until November 2000, 595 patients were randomized to three cycles of epirubicin (E) 110 mg/m2 followed by three cycles of paclitaxel (T) 250 mg/m2 followed by three cycles of "intensified" CMF (cyclophosphamide 840 mg/m2, methotrexate 47 mg/m2 and fluorouracil 840 mg/m2) or to four cycles of E, followed by four cycles of CMF. HER-2 was assessed by immunohistochemistry (IHC) in 394 patients, and by fluorescence in situ hybridization (FISH) in cases scored as 2+ by IHC. VEGF was evaluated in 323 patients by IHC. Results. HER-2 overexpression was detected in 123 patients (31%) and high expression of VEGF in 233 (72%). The rate of HER-2 overexpression was significantly higher in patients with positive VEGF staining (35% vs. 21%, p = 0.02). Overexpression of HER-2 was significantly associated with negative hormonal status, high histologic grade and larger tumors. HER-2 overexpression was a significant negative predictor of DFS (p = 0.002), but not of OS. Adjusting for HER-2 overexpression, DFS and OS did not significantly differ between treatment groups. Positive VEGF staining was not associated with receptor status, number of positive nodes, grade, tumor size, incidence of relapse or death. Conclusions. For both treatments, HER-2 overexpression was a significant negative prognostic factor for DFS but not for OS, while high expression of VEGF was not significantly associated to either DFS or OS. No predictive ability of HER-2 status or VEGF overexpression for T treatment was evident. © Springer 2006