The up-regulation profiles of p21WAF1/CIP1 and RUNX1/AML1 correlate with myometrial infiltration in endometrioid endometrial carcinoma.

We have recently described RUNX1/AML1 up-regulation in endometrioid endometrial carcinoma (EEC), proposing that it could play a role during the initial steps of myometrial infiltration. Some cell cycle regulators, including the cyclin-dependent kinase inhibitor p21WAF1/CIP1, have been described as targets of RUNX1/AML1. In this study, we have attempted to address the question of whether RUNX1/AML1, acting both as a gene transcription activator and a repressor, depending on the context, can be correlated with the expression of p21WAF1/CIP1 in gynecologic malignancies, in particular in EEC, where the role of p21(WAF1/CIP1) remains controversial. Toward this end, we analyzed p21WAF1/CIP1 expression in a large panel of EEC samples using real-time quantitative polymerase chain reaction and tissue microarray immunohistochemistry, and evaluated the extent to which RUNX1/AML1 and p21WAF1/CIP1 interacted in the EEC samples. The strong correlation found between RUNX1/AML1 and p21WAF1/CIP1 suggested cooperation between the 2 genes in EEC, especially in those tumor samples corresponding to stage IC carcinomas, infiltrating more than 50% of the myometrium. We hypothesize that p21WAF1/CIP1 and RUNX1/AML1 interact during the initial steps of tumor dissemination in EEC, and we discuss mechanisms that could underlie myometrial infiltration and/or the promotion of an invasive phenotype.