Molecular assessment of histopathological staging in squamous-cell carcinoma of the head and neck.
BACKGROUND
Surgical oncologists rely heavily on the histopathological assessment of surgical margins to ensure total excision of the tumor in patients with head and neck cancer. However, current techniques may not detect small numbers of cancer cells at the margins of resection or in cervical lymph nodes.


METHODS
We used molecular techniques to determine whether clonal populations of infiltrating tumor cells harboring mutations of the p53 gene could be detected in histopathologically negative surgical margins and cervical lymph nodes of patients with squamous-cell carcinoma of the head and neck.


RESULTS
We identified 25 patients with primary squamous-cell carcinoma of the head and neck containing a p53 mutation who appeared to have had complete tumor resection on the basis of a negative histopathological assessment. In 13 of these 25 patients, molecular analysis was positive for a p53 mutation in at least one tumor margin. In 5 of 13 patients with positive margins by this method (38 percent), the carcinoma has recurred locally, as compared with none of 12 patients with negative margins (P = 0.02 by the log-rank test). Furthermore, molecular analysis identified neoplastic cells in 6 of 28 lymph nodes (21 percent) that were initially negative by histopathological assessment.


CONCLUSIONS
Among specimens initially believed to be negative by light microscopy, a substantial percentage of the surgical margins and lymph nodes from patients with squamous-cell carcinoma of the head and neck contained p53 mutations specific for the primary tumor. Patients with these positive margins appear to have a substantially increased risk of local recurrence. Molecular analysis of surgical margins and lymph nodes can augment standard histopathological assessment and may improve the prediction of local tumor recurrence.
Brennan
J A
JA
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2195.
Mao
L
L
Hruban
R H
RH
Boyle
J O
JO
Eby
Y J
YJ
Koch
W M
WM
Goodman
S N
SN
Sidransky
D
D
D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D016158:Genes, p53; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015580:Mohs Surgery; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D009367:Neoplasm Staging; D011336:Probability; D016896:Treatment Outcome
D004273:DNA, Neoplasm