Elsevier

American Journal of Otolaryngology

Volume 25, Issue 4, July–August 2004, Pages 231-239
American Journal of Otolaryngology

Prognostic significance of p53 and FHIT in advanced oropharyngeal carcinoma

Presented at the Annual Meeting of the American Radium Society, San Diego, CA, April 25–29, 2001.
https://doi.org/10.1016/j.amjoto.2004.01.001Get rights and content

Abstract

Objective

To determine the prognostic significance of p53 and fragile histidine triad (FHIT) expression in advanced oropharyngeal squamous cell carcinoma.

Study design

A retrospective collection of clinical data was correlated with the protein expression.

Method

The expression of p53 and FHIT in specimens from patients with previously untreated advanced squamous cell carcinoma of the oropharynx was determined by immunohistochemistry. The expression of p53 and FHIT was statistically correlated with survival outcome. The primary endpoints were overall survival and disease-free survival.

Results

Thirty-four patients were analyzed in this study. Overexpression of p53 was observed in 41.2% (14/34) of tumors and was associated with a trend toward an improved overall survival using univariate (P = .1088, risk ratio [RR] = 0.503) and multivariate (P = .1533, RR = 0.470) analyses. Marked reduction or complete absence of FHIT expression was observed in 57.6% (19/33) of tumors. Patients with tumors showing no reduction in FHIT expression had a lower overall survival using univariate (P = .04, RR = 2.27) and multivariate (P = .013, RR = 4.41) analyses.

Conclusion

Overexpression of p53 predicted a trend toward an improved prognosis, whereas no reduction in FHIT expression predicted a significantly poorer outcome in patients with advanced oropharyngeal cancer.

Section snippets

Clinical data

Between 1983 to 1994, a retrospective clinical review of 40 patients who underwent first-time treatment for advanced oropharyngeal carcinoma was performed. Three patients were eliminated from the study because of insufficient tumor sample for p53 and FHIT immunohistochemical analysis. One more patient was eliminated from the FHIT group because of insufficient tumor sample. Two patients did not have sufficient follow-up data. One additional patient was eliminated from the final analysis because

Clinical data

Thirty-four patients were analyzed in this study. Seven of the patients were women, and 27 were men. The patient’s age at the time of diagnosis ranged from 37 to 77 years, with a mean age of 56 years. All 34 patients were smokers and also had a history of frequent ethanol consumption. The range of follow-up for patients was 2 to 161 months with primary endpoints of overall and disease-free survival. All patients had a minimum follow-up of 2 years, except for patients who reached clinical

Discussion

The study of molecular markers in malignant tumors enables us to understand the events that are occurring at the subcellular level and their association with oncogenesis. These events may have a correlation with tumor biologic behavior and clinical prognosis. Poor survival is associated with advanced squamous cell carcinoma of the oropharynx despite newer multimodality treatment regimens. Many patients present with bulky, infiltrating tumors with associated metastatic disease. Molecular

Conclusion

In this initial study of patients with advanced carcinoma of the oropharynx, increased expression of p53 predicted a trend toward an improved prognosis. Contrary to previous published studies, patients with no reduction of expression of FHIT had a significantly poorer survival outcome. In the future, prospective clinical trials must be performed before these molecular markers can be used in treatment decisions.

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    Also, a microsatellite locus on FHIT is found to play a role in familial prostate carcinomas [19]. There are many studies which point to relationships between the decrease in FHIT expression and the clinical course and prognosis of different malignancies [12,14,22,23,28]. In addition to these, there are different studies, which give valuable information on FHIT expression in normal tissues [5,27].

  • Oropharyngeal Squamous Cell Carcinoma Treated With Radiotherapy or Radiochemotherapy: Prognostic Role of TP53 and HPV Status

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    In the case of SCC, however, some researchers have found that p53 expression is not associated with either a favorable or unfavorable outcome in HNSCC (16), pharyngeal SCC (17), or oral SCC and OPSCC (18–20). Still other authors (21–25) have claimed to have observed a significant correlation between low p53 expression and poor survival in HNSCC, whereas yet others (26, 27) observed a positive correlation in OPSCC patients treated primarily with surgery. Specifically, these investigators found an increased survival in patients with p53 overexpression (27) and a higher risk of recurrence in patients with lower p53 expression.

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Supported by the American Cancer Society, Atlanta, GA (CRTG-99-246-01-CCE).

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