This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van Houten, V. M. M. Articles by Brakenhoff, R. H. Search for Related Content PubMed PubMed Citation Articles by van Houten, V. M. M. Articles by Brakenhoff, R. H.

Molecular Diagnosis of Surgical Margins and Local Recurrence in Head and Neck Cancer Patients

A Prospective Study

Departments of ¹ Otolaryngology/Head-Neck Surgery, ² Pathology, and ³ Clinical Epidemiology and Biostatistics, Vrije Universiteit Medical Center, Amsterdam, the Netherlands

ABSTRACT

Purpose: Approximately 10–30% of surgically treated head and neck cancer patients develop local recurrences while the resection margins are histologically tumor free. These recurrences may arise from cancer cells left behind but not detected by the pathologist, or they may develop from precursor lesions adjacent to the tumor that were not completely resected. We have investigated whether TP53-mutated DNA in the surgical margins is suitable to identify patients with head and neck squamous cell carcinoma at risk for local and locoregional recurrence.

Experimental Design: In a prospective cohort study of 76 patients with histologically tumor-free margins, the presence of TP53-mutated DNA was determined in the surgical margins using the phage plaque assay and correlated to clinical outcome. Immunostaining of the molecular-positive margins for mutated p53 protein was used to identify whether unresected precursor lesions or residual tumor cells were left behind.

Results: The absence of TP53-mutated DNA in surgical margins was significantly associated with remaining free of local and locoregional recurrence (P = 0.027 and P = 0.028, respectively). Moreover, the presence of TP53-mutated DNA in the surgical margins was an independent prognosticator for locoregional recurrence (relative risk = 7.1; P = 0.021; 95% confidence interval, 0.9–56). In 20% of the cases, the presence of TP53-mutated DNA in the surgical margins was found to be related to the presence of tumor-related precursor lesions.

Conclusions: This study shows the value of TP53-mutated DNA as a molecular marker to predict locally recurrent head and neck squamous cell carcinoma. The observation that all patients who were negative for TP53-mutated DNA in the surgical margins remained free of local recurrence raises hope that molecular analysis of histologically tumor-free surgical margins can be exploited to decide on postoperative radiotherapy. Furthermore, our data provide evidence that local recurrences originate mainly from tumor cells left behind but also originate, in part, from unresected precursor lesions.

This article has been cited by other articles:

				X. Huang, S. Pateromichelakis, A. Hills, M. Sherriff, A. Lyons, J. Langdon, E. Odell, P. Morgan, J. Harrison, and M. Partridge p53 Mutations in Deep Tissues Are More Strongly Associated with Recurrence than Mutation-Positive Mucosal Margins Clin. Cancer Res., October 15, 2007; 13(20): 6099 - 6106. [Abstract] [Full Text] [PDF]

				K. Gaballah, A. Hills, D. Curiel, G. Hallden, P. Harrison, and M. Partridge Lysis of Dysplastic but not Normal Oral Keratinocytes and Tissue-Engineered Epithelia with Conditionally Replicating Adenoviruses Cancer Res., August 1, 2007; 67(15): 7284 - 7294. [Abstract] [Full Text] [PDF]

				S. Zhou, S. Kachhap, W. Sun, G. Wu, A. Chuang, L. Poeta, L. Grumbine, S. K. Mithani, A. Chatterjee, W. Koch, et al. Frequency and phenotypic implications of mitochondrial DNA mutations in human squamous cell cancers of the head and neck PNAS, May 1, 2007; 104(18): 7540 - 7545. [Abstract] [Full Text] [PDF]

				W. H. Westra and D. Sidransky Fluorescence Visualization in Oral Neoplasia: Shedding Light on an Old Problem. Clin. Cancer Res., November 15, 2006; 12(22): 6594 - 6597. [Full Text] [PDF]

				C. F. Poh, L. Zhang, D. W. Anderson, J. S. Durham, P. M. Williams, R. W. Priddy, K. W. Berean, S. Ng, O. L. Tseng, C. MacAulay, et al. Fluorescence Visualization Detection of Field Alterations in Tumor Margins of Oral Cancer Patients. Clin. Cancer Res., November 15, 2006; 12(22): 6716 - 6722. [Abstract] [Full Text] [PDF]

				B Perez-Ordonez, M Beauchemin, and R C K Jordan Molecular biology of squamous cell carcinoma of the head and neck. J. Clin. Pathol., May 1, 2006; 59(5): 445 - 453. [Abstract] [Full Text] [PDF]

				B. J.M. Braakhuis, R. H. Brakenhoff, and C. R. Leemans Second Field Tumors: A New Opportunity for Cancer Prevention? Oncologist, August 1, 2005; 10(7): 493 - 500. [Abstract] [Full Text] [PDF]