Cyclin D1 and p53 overexpression predicts multiple primary malignant neoplasms of the hypopharynx and esophagus

Arch Otolaryngol Head Neck Surg. 1999 Dec;125(12):1351-4. doi: 10.1001/archotol.125.12.1351.

Abstract

Background: Multiple primary upper aerodigestive tract carcinomas can occur in up to 15% of patients. We have shown previously that half of the patients with multiple upper aerodigestive tract squamous cell carcinomas are initially seen with synchronous tumors. Most metachronous squamous cell carcinomas become manifest within 3 years.

Objective: To examine the expression of 2 proteins-cyclin D1 and p53--in an attempt to predict the occurrence of multiple primary malignant neoplasms (MPs).

Materials and methods: Monoclonal antibodies to cyclin D1 (DCS-6 [dilution, 1:50]. Novocastra Laboratories Ltd, Newcastle, England) and p53 (DO-7 [dilution, 1-100], Dako Corp, Carpinteria, Calif) proteins were used. Resection specimens from a total of 47 patients, 12 patients with MP and 35 patients with nonmultiple primary malignant neoplasms, were analyzed. Those in the nonmultiple primary malignant neoplasm group had longer than 3 years' follow-up to ascertain the absence of MP.

Results: Tumor overexpression of cyclin D1 was significantly associated with the development of MP (P<.01). Tumor overexpression of p53 was also frequent in patients with MP although statistical significance was not achieved. The combination of these 2 parameters was an even greater predictor of MP (P<.001).

Conclusions: Overexpression of cyclin D1 and p53 proteins was highly correlated with the development of MP. Additional studies are necessary to confirm this finding. Immunohistochemical evaluation of primary squamous cell carcinomas for cyclin D1 and p53 overexpression may become an important fact of surgical pathologic reporting for primary upper aerodigestive tract squamous cell carcinomas.

MeSH terms

  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cyclin D1 / genetics*
  • Cyclin D1 / metabolism
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Hypopharyngeal Neoplasms / genetics*
  • Hypopharyngeal Neoplasms / metabolism
  • Hypopharyngeal Neoplasms / pathology
  • Neoplasms, Multiple Primary / genetics*
  • Neoplasms, Multiple Primary / metabolism
  • Neoplasms, Multiple Primary / pathology
  • Predictive Value of Tests
  • Prognosis
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Tumor Suppressor Protein p53
  • Cyclin D1