p53 protein accumulation and p53 gene mutation in esophageal carcinoma. A molecular and immunohistochemical study with clinicopathologic correlations.
BACKGROUND
p53 gene mutation and p53 protein accumulation are common in human cancer. However, their clinical significance is controversial and p53 accumulation may not correlate with gene mutation. The current study investigates the occurrence of p53 alterations in esophageal carcinoma, the correlation between the analyses at the gene and protein level, and their prognostic significance.


METHODS
A series of 74 esophageal carcinomas (46 squamous cell carcinomas, 21 Barrett's adenocarcinomas, and 7 undifferentiated carcinomas) was studied by single strand conformation polymorphism (SSCP) analysis and immunohistochemistry (IHC) to detect p53 mutation and accumulation, respectively.


RESULTS
p53 mutations in exons 5-8 were detected in 53% of the carcinomas whereas p53 accumulation was observed in 57% of cases. Comparing SSCP and IHC, there were 27 discordant cases (38%). Overall, only 20 tumors (27%) did not display p53 mutation and/or p53 accumulation. No associations were found between p53 aberrations and clinicopathologic parameters, including patients age and gender tumor type, stage, and grade. p53 protein accumulation and p53 gene mutation were not related to patient survival by univariate or multivariate analysis in esophageal carcinomas.


CONCLUSIONS
p53 aberrations are very common in esophageal carcinomas. However, p53 gene mutation and p53 protein accumulation have a significant discordance, suggesting that p53 function may be inactivated by mechanisms other than mutation. p53 aberrations do not independently predict prognosis in esophageal tumors.
Coggi
G
G
Department of Pathology II, Ospedale S. Paolo, Milan, Italy.
Bosari
S
S
Roncalli
M
M
Graziani
D
D
Bossi
P
P
Viale
G
G
Buffa
R
R
Ferrero
S
S
Piazza
M
M
Blandamura
S
S
Segalin
A
A
Bonavina
L
L
Peracchia
A
A
D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics; D001471:Barrett Esophagus / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000235:genetics; D015342:DNA Probes; D004938:Esophageal Neoplasms / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D015342:DNA Probes; D016159:Tumor Suppressor Protein p53