system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Adult, Aged, Base Pair Mismatch, Cell Cycle Proteins, Cell Division, Combined Modality Therapy, Cyclin-Dependent Kinase Inhibitor p21, Cyclins, DNA Mutational Analysis, DNA Repair, DNA-Binding Proteins, Disease-Free Survival, Female, Genes, p53, Humans, Immunohistochemistry, Ki-67 Antigen, Longitudinal Studies, Male, Middle Aged, MutS Homolog 2 Protein, Neoadjuvant Therapy, Polymorphism, Single-Stranded Conformational, Prognosis, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, Rectal Neoplasms, Survival Rate, bcl-2-Associated X Protein.
user
Does dynamic expression profile of p21WAF1/CIP1 and Ki-67 predict survival in rectal carcinoma treated with preoperative radiochemotherapy? Context: We investigated p53 and its downstream effectors p21WAF1/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. Expression of p53, BAX, p21WAF1/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. 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.
assistant
These findings are novel and support the clinical relevance of p21 in the suppression of both proliferation and apoptosis. Thus, the dynamic induction of p21WAF1/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. Final Decision: yes