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Overexpression of p53 in Tumor-distant Epithelia of Head and Neck Cancer Patients Is Associated with an Increased Incidence of Second Primary Carcinoma
Second primary carcinoma is a peculiar feature of head and neck cancer and represents a form of treatment failure distinct from the recurrence of the primary tumor. Whether altered p53 expression in tumor-distant epithelia at the time of diagnosis is of clinical value as a biomarker for second prima...
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Published in: | Clinical cancer research 2001-02, Vol.7 (2), p.290-296 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
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Summary: | Second primary carcinoma is a peculiar feature of head and neck cancer
and represents a form of treatment failure distinct from the recurrence
of the primary tumor. Whether altered p53 expression in tumor-distant
epithelia at the time of diagnosis is of clinical value as a biomarker
for second primary carcinoma development has not been rigorously
answered because of the lack of long-term follow-up studies involving a
sufficiently large patient cohort. In this prospective study, we have
investigated p53 expression in tumor-distant epithelia and in the
corresponding primary tumors of 105 head and neck cancer patients by
immunohistochemistry on frozen sections. After a median follow-up of 55
months, the clinical course of disease parameters, i.e.,
local recurrences, lymph node and distant metastasis, incidence of
second primary carcinoma, and survival, was evaluated. Overexpression
of p53 in tumor-distant epithelia was found in 49 patients (46.7%),
and it was independent of the p53 protein status of the primary tumor
and of the tumor site, size, stage, and grading. Mucosal p53
overexpression was not associated with local primary recurrences, lymph
node or distant metastases, or overall survival. Importantly, mucosal
p53 overexpression, but not overexpression in the primary tumors, was
significantly associated with an increased incidence of second primary
carcinomas ( P = 0.0001; Fisher’s exact test). When
the times to second primary tumor occurrence were analyzed by the
Kaplan-Meier method, the difference remained significant
( P = 0.005; log rank test). We conclude that IHC
staining for p53 overexpression in tumor-distant epithelia provides a
simple and rapid tool to identify head and neck cancer patients at
increased risk of developing second primary tumors. Because p53
overexpression in these epithelia in our patient cohort was
specifically associated with second primary cancer but not with
recurrences, at least a fraction of the second primary cancers appears
to have resulted from genetic events in the mucosa (“field
cancerization”). |
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ISSN: | 1078-0432 1557-3265 |