ABSTRACT
OBJECTIVE: To investigate the clinical significance of p16 expression, a product of the cyclin dependent kinase inhibitor CDKN2 (also known as MTS1, multiple tumor suppressor 1) and assess its relationship with retinoblastoma protein expression in the pathogenesis of endometrial cancer. METHOD: p16 and pRb expression were histochemically evaluated, using p16 and RB polyclonal antibodies on paraffin sections of 27 primary endometrial adenocarcinomas with no therapy prior to surgery, through the streptavidin peroxydase conjugated method. Further analyses were carried out using the polymerase chain reaction for exon 1 gene amplification to investigate the mechanism of abnormal p16 expression. RESULT: p16 expression was detected in 100% of normal endometriums and in 74.04% of endometrial carcinomas (p < 0.05). This was significantly associated with tumor cell grade (p < 0.05). PCR analysis of exon 1 in five cases with no detectable p16 expression revealed four homozygous deletions. Additionally, the inverse correlation between RB and p16 expression was confirmed in this study, with 71.42% of tumors demonstrating inverse expression of p16 and RB (p < .005). CONCLUSION: p16 expression decrease is a significant event in endometrial carcinoma pathogenesis, and it is inversely correlated to tumor cell grade. Exon 1 homozygous deletion might be one of the mechanisms of loss of p16 expression. The p16/pRb growth suppressor pathway is targeted in human endometrial carcinoma.
