p53 mutation as a prognostic marker in advanced laryngeal carcinoma. Department of Veterans Affairs Laryngeal Cancer Cooperative Study Group.
OBJECTIVE
To determine the relationship of p53 mutations in advanced laryngeal carcinomas to p53 immunohistochemistry, organ preservation, and patient survival.


METHODS
Paraffin-embedded tumor specimens were obtained from patients enrolled in the Department of Veterans Affairs Laryngeal Cancer Cooperative Study, a multi-institutional randomized clinical trial comparing induction chemotherapy (cisplatin and fluorouracil) plus radiation therapy surgery plus postoperative radiation therapy. Tumor specimens were analyzed for p53 mutations in exons 5 through 8 by using single-strand conformational polymorphism (SSCP) analysis followed by DNA sequencing of all variants. Five-year follow-up data were available for all patients studied.


METHODS
Forty-four patients enrolled in the Department of Veterans Affairs Laryngeal Cancer Cooperative Study from whom paraffin-embedded tumor specimens were readily available.


RESULTS
p53 immunostaining did not correlate with p53 SSCP and DNA sequencing results. More than half (62% [16/26]) of the tumors that overexpressed p53 immunohistochemically did not have a detectable p53 gene mutation. Similarly, 39% (7/18) of tumors that did not overexpress p53 did have a p53 gene mutation. p53 mutations were present in 39% of tumors tested. Mutations within exon 5 made up 41% of p53 gene mutations in laryngeal carcinomas. Transitions were the most common type of mutation in this study (92% of mutations).


CONCLUSIONS
The presence of a p53 mutation as detected by SSCP is associated with decreased patient survival. Further study is required to confirm this relationship and to determine whether specific p53 mutations predict organ preservation.
Bradford
C R
CR
Department of Otolaryngology/Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, USA.
Zhu
S
S
Poore
J
J
Fisher
S G
SG
Beals
T F
TF
Thoraval
D
D
Hanash
S M
SM
Carey
T E
TE
Wolf
G T
GT
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D003131:Combined Modality Therapy; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D017422:Sequence Analysis, DNA; D015996:Survival Rate