p53 expressions: predicting recurrence and second primary tumors in head and neck squamous cell carcinoma.
BACKGROUND
The survival rate for head and neck squamous cell carcinoma remains poor despite therapeutic advances over the last two decades. For patients with disease confined to the head and neck, there are two major and biologically distinct patterns of treatment failures after definitive therapy: recurrence of primary disease and development of second primary tumors. Understanding the biological basis of patterns of treatment failure after definitive therapy is needed to guide the development of adjuvant treatment and strategies to prevent second primary tumors.


OBJECTIVE
To determine whether expression of the p53 protein has prognostic significance and/or is associated with patterns of treatment failure, we examined protein expression in primary tumor specimens of patients with head and neck squamous cell carcinoma.


METHODS
Immunohistochemical analysis with a monoclonal antibody (DO7) specific for p53 protein was used to detect expression of the protein in formalin-fixed, paraffin-embedded tumor samples from 69 head and neck cancer patients treated with definitive local therapy (surgery and/or radiotherapy) between January 1980 and October 1983 at The University of Texas M. D. Anderson Cancer Center. We quantitated p53 protein expression and assessed its association with duration of patient survival, patterns of treatment failure (recurrence of primary tumor and development of second primary tumor), and other clinical parameters. All reported P values resulted from two-sided statistical tests.


RESULTS
We found detectable levels of p53 protein expression in the tumor cell nuclei of 41 of 69 patients. Thirty-six (52%) of 69 patients whose tumors exhibited p53 protein expression in greater than or equal to 10% of the cell nuclei were grouped as p53 positive, and 33 (48%) of 69 patients whose tumors exhibited less than 10% nuclear expression were groups as p53 negative. The clinical characteristics of the patients in the p53-positive, and p53-negative groups were well balanced. Overall survival was significantly lower, and the times to tumor recurrence, to second primary tumors, and to any treatment failure were significantly shorter in the p53-positive group that in the p53-negative group (P=.0002, P=.047, P=.003, and P=.0009, respectively), mainly because the p53 positivity was associated with earlier development of tumor recurrence and second primary tumors. The rate of second primary tumor development per person per year was also significantly higher in the p53-positive group that in the p53-negative group. By use of multivariate analysis according to the Cox regression model, p53 expression status was identified as the most significant predictor of overall survival duration (P=.007), time to tumor recurrence (P=.053), time to second primary tumors (P=.035), and time to any treatment failure (P=.004).


CONCLUSIONS
The expression of p53 protein in primary head and neck squamous cell carcinoma was significantly predictive of shorter survival because of its association with earlier development of both tumor recurrence and second primary tumors. Thus, p53 expression may be a valuable marker for identifying individuals at high risk of developing a recurrence of primary disease and second primary tumors who may benefit from adjuvant therapy and chemoprevention after definitive local therapy.
Shin
D M
DM
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, 77030, USA.
Lee
J S
JS
Lippman
S M
SM
Lee
J J
JJ
Tu
Z N
ZN
Choi
G
G
Heyne
K
K
Shin
H J
HJ
Ro
J Y
JY
Goepfert
H
H
Hong
W K
WK
Hittelman
W N
WN
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000401:mortality; D005260:Female; D006258:Head and Neck Neoplasms / Q000737:chemistry* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000209:etiology*; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000209:etiology*; D015996:Survival Rate; D017211:Treatment Failure; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D016159:Tumor Suppressor Protein p53