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Immunohistochemical staining patterns of p53 can serve as a surrogate marker for TP53 mutations in ovarian carcinoma: an immunohistochemical and nucleotide sequencing analysis
Ist Teil von
Modern pathology, 2011-09, Vol.24 (9), p.1248-1253
Ort / Verlag
New York: Nature Publishing Group US
Erscheinungsjahr
2011
Quelle
MEDLINE
Beschreibungen/Notizen
Immunohistochemical staining for p53 is used as a surrogate for mutational analysis in the diagnostic workup of carcinomas of multiple sites including ovarian cancers. Strong and diffuse immunoexpression of p53 is generally interpreted as likely indicating a
TP53
gene mutation. The immunoprofile that correlates with wild-type
TP53
, however, is not as clear. In particular, the significance of completely negative immunostaining is controversial. The aim of this study was to clarify the relationship of the immunohistochemical expression of p53 with the mutational status of the
TP53
gene in ovarian cancer. A total of 57 ovarian carcinomas (43 high-grade serous ovarian/peritoneal carcinomas, 2 malignant mesodermal mixed tumors (carcinosarcomas), 2 low-grade serous carcinomas, 4 clear cell carcinomas, 1 well-differentiated endometrioid carcinoma, and 5 carcinomas with mixed epithelial differentiation) were analyzed for
TP53
mutations by nucleotide sequencing (exons 4–9), and subjected to immunohistochemical analysis of p53 expression. Thirty six tumors contained functional mutations and 13 had wild type
TP53.
Five tumors were found to harbor known
TP53
polymorphism and changes in the intron region were detected in three. Tumors with wild-type
TP53
displayed a wide range of immunolabeling patterns, with the most common pattern showing ≤10% of positive cells in 6 cases (46%). Mutant
TP53
was associated with 60–100% positive cells in 23 cases (64% of cases). This pattern of staining was also seen in three cases with wild-type
TP53.
Tumors that were completely negative (0% cells staining) had a mutation of
TP53
in 65% of cases and wild-type
TP53
in 11%. Combining two immunohistochemical labeling patterns associated with
TP53
mutations (0% and 60–100% positive cells), correctly identified a mutation in 94% of cases (
P
<0.001). Immunohistochemical analysis can be used as a robust method for inferring the presence of a
TP53
mutation in ovarian carcinomas. In addition to a strong and diffuse pattern of p53 expression (in greater than 60% of cells), complete absence of p53 immunoexpression is commonly associated with a
TP53
mutation. Accordingly, this latter pattern, unlike low-level expression (10–50% cells), should not be construed as indicative of wild-type
TP53
.