Analysis of PTEN, VEGF, HER2 and P53 Status in Determining Colorectal Cancer Benefit from Bevacizumab Therapy

Abstract

Background: No factor has thus far been identified to predict the efficacy of bevacizumab therapy for colorectal cancer. We here therefore studied PTEN, VEGF, HER2 and p53 by immunohistochemistry as possible prognostic and predictive factors. Materials and Methods: A total of 34 retrospectively collected tumor samples were evaluated, all from patients receiving bevacizumab-based regimens. VEGF-A, PTEN, HER2, p53 were assessed and data was compared with clinicopathologic characteristics of patients and the bevacizumab response rate. Results: In this study, the median age of the 34 metastatic colorectal cancer patients was 55.5 (24-75), twelve (35.3%) being women and 22 (64.7%) men. PTEN, VEGF, HER2, p53 expressions were compared with bevacizumab response and other chacteristics of disease. Statistical significant differences were not found between bevacizumab response rates and different expression levels of VEGF, PTEN, HER2 and p53 (respectively p=0.256, p=0.832, p=0.189, p=0.131). However, a survival difference was noted in the VEGF expression negative group (median OS:55 months; 95%CI, 22-88 months) (p=0.01). There was no statistically significant OS difference in other groups (PTEN p=0.6, HER2 p=0.189, p53 p=0.13). Conclusions: We did not find any predictive factor for BV therapy in our study. VEGF negative expression could be an important prognostic factor in metastatic colorectal carcinoma.

VEGF-A Expression Correlates with TP53 Mutations in Non–Small Cell Lung Cancer: Implications for Antiangiogenesis Therapy

“…However, this association may not hold true for all tumor types. For instance, benefit from bevacizumab could not be correlated with TP53 status in metastatic colorectal cancer (15,16). On the other hand, these prior studies in colorectal cancer had significant differences in methodology that might have influenced outcome.…”

The significance of combining VEGFA, FLT1, and KDR expressions in colon cancer patient prognosis and predicting response to bevacizumab

“…Previous reports investigating the association between mutational status of p53 and response to bevacizumab were contradictory; some reports showed that p53 status did not affect the efficacy of bevacizumab, 41 , 42 while one report showed that patients with p53-positive (expression) tumors had a significantly longer survival when treated with bevacizumab with chemotherapy; 43 another report showed that the progression-free survival was significantly longer with bevacizumab-containing regimens in patients with mutant p53 tumors, but not in those with wild-type p53 tumors. 44 In the present study, our results show that the three-gene signature is prognostic only in tumors with mutant p53, but not in those with wild-type p53, suggesting that VEGFA -mediated angiogenesis may play an important role in a p53 mutant genetic background.…”

PTEN in Colorectal Cancer: Shedding Light on Its Role as Predictor and Target

“…In 2012, a retrospective analysis compared the PTEN expression (assessed by means of IHC) of 34 tumor samples from patients affected by mCRC treated with bevacizumab-based regimens with treatment activity [35]. No statistically significant differences were found between the response rate and different expression levels of PTEN ( p = 0.832).…”