Molecular diagnosis of surgical margins and local recurrence in head and neck cancer patients: a prospective study.
OBJECTIVE
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.


METHODS
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.
van Houten
Viola M M
VM
Departments of Otolaryngology/Head-Neck Surgery, Pathology, and Clinical Epidemiology and Biostatistics, Vrije Universiteit Medical Center, Amsterdam, the Netherlands.
Leemans
C René
CR
Kummer
J Alain
JA
Dijkstra
Janny
J
Kuik
Dirk J
DJ
van den Brekel
Michiel W M
MW
Snow
Gordon B
GB
Brakenhoff
Ruud H
RH
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D005260:Female; D016158:Genes, p53; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D018365:Neoplasm, Residual; D011446:Prospective Studies; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D012008:Recurrence; D012306:Risk; D013997:Time Factors
D012313:RNA; D004247:DNA