Expression and alteration of p53 and p21(waf1/cip1) influence the sensitivity of chemoradiation therapy for esophageal cancer

Hepatogastroenterology. 1998 Sep-Oct;45(23):1497-504.

Abstract

Background/aims: In vitro analyses have been demonstrated that wild type p53 and p21(waf1/cip1) proteins regulate cellular proliferation and sensitivity of anticancer agents, however, the roles of p53 and p21(waf1/cip1) expression on the response to the chemoradiation therapy for human esophageal squamous cell cancer have not been investigated.

Methodology: With an immunohistochemical method using specimens before and after the chemoradiation therapy, we investigate in this report the influence of the p53 and p21(waf1/cip1) expression on the chemoradiation therapy response or alteration of these protein expressions by chemoradiation therapy in thirteen esophageal squamous cell cancer patients who received our recently developed chemoradiation therapy.

Results: In the biopsy specimens before the chemoradiation therapy, 82% of the responders and 71% of patients with down T-classification had either a p53-/p21+ or p53+/p21+ phenotype. Eighty two percent and 46% of the cases with these two phenotypes showed complete or partial response and down T-classification, respectively. After the chemoradiation therapy, 73% of the responders and 71% of the patients with down T-classification had either a p53-/p21+ or p53+/p21+ phenotype. Eighty eight percent and 56% of the cases with these two phenotypes showed complete or partial response and down T-classification, respectively. Comparative analysis before and after the chemoradiation therapy revealed that four patients had an alteration of p53 and p21(waf1/cip1) expression in association with the therapeutic response.

Conclusions: These results suggest that wild type p53 or p21(waf1/cip1) expression relates with and can be altered by the chemoradiation therapy, which could influence the therapeutic efficacy.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / therapy*
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / analysis*
  • Cyclins / genetics
  • Drug Resistance, Neoplasm
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / therapy*
  • Fluorouracil / administration & dosage
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Phenotype
  • Radiation Tolerance
  • Radiotherapy Dosage
  • Tumor Suppressor Protein p53 / analysis*
  • Tumor Suppressor Protein p53 / genetics

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Tumor Suppressor Protein p53
  • Cisplatin
  • Fluorouracil