In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 21, No. 18 ( 2003-09-15), p. 3391-3401
Abstract:
Purpose: We investigated p53 and its downstream effectors p21 WAF1/CIP1 , BAX, and hMSH2 as well as the proliferation marker Ki-67 (mki-67/MIB-1) in patients undergoing preoperative radiochemotherapy for rectal carcinoma to identify prognostic and predictive factors. The focus of this study was on the dynamics of these genetic markers in a longitudinal study—that is, before and after radiochemotherapy. Patients and Methods: Expression of p53, BAX, p21 WAF1/CIP1 , Ki-67, and hMSH2 was investigated by immunohistochemistry in pre- and posttherapeutic tumor samples in 66 patients. Tumor DNA was screened for p53 mutations by single-strand conformation polymorphism–polymerase chain reaction (SSCP-PCR). Paired tumor samples (pretherapy and posttherapy) were collected prospectively. Results: Patients with a decrease in p21 expression following radiochemotherapy had better disease-free survival (P = .03). Similarly, patients with an increase in proliferative activity as measured by increased Ki-67 expression posttherapy had better disease-free survival (P 〈 .005). In addition, we observed a significantly better prognosis for patients with high hMSH2 expression. In contrast, pretherapeutic levels of p53, BAX, or p21 expression and p53 mutation had no prognostic value, indicating that the combination of radiotherapy and chemotherapy might override defects in these genes. Conclusion: These findings are novel and support the clinical relevance of p21 in the suppression of both proliferation and apoptosis. Thus, the dynamic induction of p21 WAF1/CIP1 was associated with a lower proliferative activity but an ultimately worse treatment outcome following neoadjuvant radiochemotherapy and tumor resection. Induction of p21, therefore, represents a novel resistance mechanism in rectal cancer undergoing preoperative radiochemotherapy.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2003.07.077
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2003
detail.hit.zdb_id:
2005181-5
