P16 alterations increase the metastatic potential of endometrial carcinoma.
OBJECTIVE
The aim of this study was to investigate the role of p16 in tumorigenesis of endometrial carcinoma (EC).


METHODS
Expression of p16 protein was analyzed using immunohistochemistry. The methylation status of p16 promoter region was determined by methylation-specific PCR. Deletion analysis of the p16 gene was performed by PCR-analyses.


RESULTS
Aberrant protein expression of p16 was observed in 18 of 46 (39.2%) ECs and correlated significantly with p16 alterations, including gene deletions in 26 of 46 (56.5%) ECs and promoter hypermethylation in 8 of 46 (17.4%) ECs (p<0.001). A significant increase in the frequency of p16 alterations from early stage (I-II) to advanced stage (III-IV) ECs was observed (p=0.002). There was no significant correlation between p16 protein expression and the clinico-pathological features of EC. The development of metastases correlated significantly with the frequency of p16 alterations: p16 alterations were detected in 14 of 15 (93.3%) PTs with metastases and in only 18 of 31 (58.1%) PTs without metastases (p=0.018). The genetic comparison of 15 primary ECs and their paired metastases revealed that in most of the cases the deleted region of p16 gene remains the same or becomes larger during the progression from primary tumor to its corresponding metastases.


CONCLUSIONS
Our results suggest that p16 alterations and particularly p16 gene deletions in ECs are associated with increased incidence of metastases.
Ignatov
Atanas
A
Department of Obstetrics and Gynecology, Otto-von-Guericke University, Magdeburg, Germany.
Bischoff
Joachim
J
Schwarzenau
Christa
C
Krebs
Thomas
T
Kuester
Doerthe
D
Herrmann
Kerstin
K
Costa
Serban D
SD
Roessner
Albert
A
Semczuk
Andrzej
A
Schneider-Stock
Regine
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019175:DNA Methylation; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D017353:Gene Deletion; D019942:Genes, p16; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic
C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins