Differential expression of P16 and P21 in benign and malignant uterine smooth muscle tumors.
OBJECTIVE
The diagnosis of benign and malignant uterine smooth muscle tumors depends on morphologic criteria such as nuclear atypia, coagulative tumor cell necrosis and mitotic activity. Most of these tumors are readily classifiable into benign or malignant categories using these criteria. However, the distinction between leiomyomas and leiomyosarcomas may at times be problematic. Hence, it would be useful to have additional markers which could help to distinguish these tumors. The aim of the study was to evaluate p16 and p21 expressions in uterine smooth muscle tumors and determine whether p16 and p21 have a potential value in the differential diagnosis of problematic cases. In addition, we evaluated whether the differential expression of p16 and p21 in uterine leiomyosarcomas correlated with tumor recurrence and patient survival.


METHODS
p16 and p21 expressions were investigated by immunohistochemistry from paraffin-embedded tissues in 53 cases of uterine smooth muscle tumors consisting of 15 cases of leiomyoma, 14 cases of atypical leiomyoma (leiomyoma with bizarre nuclei), 3 cases of smooth muscle tumor of uncertain malignant potential (STUMP) and 21 cases of leiomyosarcoma. Cases were evaluated with respect to both staining percentage and intensity.


RESULTS
There was a statistically significant difference in p16 and p21 staining percentage and intensity between leiomyosarcomas and the other groups. There was no difference in p16 and p21 expressions between leiomyomas, atypical leiomyomas (leiomyoma with bizarre nuclei) and STUMPs. Multivariate analysis showed that the tumor stage was the only independent significant prognostic factor for overall survival in leiomyosarcomas. Neither p16 nor p21 was correlated with disease-free or overall survival.


CONCLUSIONS
Our findings suggested that p16 and p21 may be of value as an adjunct to conventional morphologic criteria in the assessment of problematic uterine smooth muscle tumors.
Ünver
Nurcan Uluskan
NU
Department of Pathology, Osmangazi University Medical Faculty, Eskişehir, Turkey.
Acikalin
Mustafa Fuat
MF
Öner
Ülkü
Ü
Ciftci
Evrim
E
Ozalp
S Sinan
SS
Colak
Ertugrul
E
D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D003937:Diagnosis, Differential; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018235:Smooth Muscle Tumor / Q000378:metabolism* / Q000473:pathology; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology
C493956:CDKN1A protein, human; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009363:Neoplasm Proteins