Role of TP53 mutations in vulvar carcinomas.

TY - JOUR

T1 - Role of TP53 mutations in vulvar carcinomas.

AU - Choschzick, Matthias

AU - Hantaredja, Widianto

AU - Tennstedt, Pierre

AU - Gieseking, Frederike

AU - Wölber, Linn

AU - Simon, Ronald

PY - 2011

Y1 - 2011

N2 - Human papillomavirus (HPV)-independent development of vulvar carcinomas is common and the disruption of the TP53 pathway seems to play a key role in these tumors. Overexpression of TP53 in precursor lesions (differentiated VIN) and associated invasive carcinomas is regarded as an important diagnostic feature of this subtype of vulvar cancer. To determine the relationship of TP53 mutation status with clinicopathologic parameters, HPV status, and patient outcome, 18 squamous cell carcinomas of the vulva with TP53 overexpression along with 21 immunohistochemically TP53-negative tumors were analyzed. TP53 mutations were found in 17 (43.6%) of vulvar cancers, 18 (46.2%) tumors were HPV associated, and 8 (20.5%) carcinomas showed no relation to HPV infection or TP53 mutations. The presence of TP53 mutations was significantly linked to TP53 overexpression (P=0.002) and negative HPV status (P=0.012). The specificity of TP53 protein overexpression for the occurrence of TP53 mutations was 68.2%, with a positive predictive value of 66.7%. The most frequent mutation types were C:G ?T:A transitions (57.9%). This mutation pattern strongly indicates the important role of oxidative stress in vulvar carcinogenesis. There were no relationships between TP53 mutation status and tumor stage, grading, nodal status, depth of invasion, or patient prognosis. In summary, TP53 mutations play a crucial role in a substantial proportion of vulvar carcinomas and are probably associated to cellular oxidative stress in chronically degenerative diseases of the vulva, such as lichen sclerosus. These data support the potential utility of restoring TP53 function as a therapeutic alternative in vulvar cancer. Further studies are necessary to clarify the prognostic implications of TP53 mutations in vulvar carcinomas.

AB - Human papillomavirus (HPV)-independent development of vulvar carcinomas is common and the disruption of the TP53 pathway seems to play a key role in these tumors. Overexpression of TP53 in precursor lesions (differentiated VIN) and associated invasive carcinomas is regarded as an important diagnostic feature of this subtype of vulvar cancer. To determine the relationship of TP53 mutation status with clinicopathologic parameters, HPV status, and patient outcome, 18 squamous cell carcinomas of the vulva with TP53 overexpression along with 21 immunohistochemically TP53-negative tumors were analyzed. TP53 mutations were found in 17 (43.6%) of vulvar cancers, 18 (46.2%) tumors were HPV associated, and 8 (20.5%) carcinomas showed no relation to HPV infection or TP53 mutations. The presence of TP53 mutations was significantly linked to TP53 overexpression (P=0.002) and negative HPV status (P=0.012). The specificity of TP53 protein overexpression for the occurrence of TP53 mutations was 68.2%, with a positive predictive value of 66.7%. The most frequent mutation types were C:G ?T:A transitions (57.9%). This mutation pattern strongly indicates the important role of oxidative stress in vulvar carcinogenesis. There were no relationships between TP53 mutation status and tumor stage, grading, nodal status, depth of invasion, or patient prognosis. In summary, TP53 mutations play a crucial role in a substantial proportion of vulvar carcinomas and are probably associated to cellular oxidative stress in chronically degenerative diseases of the vulva, such as lichen sclerosus. These data support the potential utility of restoring TP53 function as a therapeutic alternative in vulvar cancer. Further studies are necessary to clarify the prognostic implications of TP53 mutations in vulvar carcinomas.

KW - Humans

KW - Female

KW - Immunohistochemistry

KW - Predictive Value of Tests

KW - Kaplan-Meier Estimate

KW - Tissue Array Analysis

KW - Mutation

KW - Carcinoma, Squamous Cell/genetics/pathology/virology

KW - Papillomavirus Infections/complications

KW - Tumor Suppressor Protein p53/genetics

KW - Vulvar Neoplasms/genetics/pathology/virology

KW - Humans

KW - Female

KW - Immunohistochemistry

KW - Predictive Value of Tests

KW - Kaplan-Meier Estimate

KW - Tissue Array Analysis

KW - Mutation

KW - Carcinoma, Squamous Cell/genetics/pathology/virology

KW - Papillomavirus Infections/complications

KW - Tumor Suppressor Protein p53/genetics

KW - Vulvar Neoplasms/genetics/pathology/virology

M3 - SCORING: Journal article

VL - 30

SP - 497

EP - 504

JO - INT J GYNECOL PATHOL

JF - INT J GYNECOL PATHOL

SN - 0277-1691

IS - 5

M1 - 5

ER -