Loss of p16 in recurrent malignant mixed mullerian tumors of the uterus

Abstract

Uterine malignant mixed müllerian tumors (MMMTs) are rare and highly aggressive malignancies with poor clinical prognoses. We examined for differences in the oncoprotein profiles of primary versus recurrent MMMTs. Five cases of recurrent uterine MMMT were examined by paraffin immunohistochemistry for the expression of p53, p16, P-cadherin, and Cerb-B2. P16, p53, and P-cadherin were each expressed in 100%, 80%, and 60% of the primary cases, respectively. Three cases expressed all three oncoproteins. All five cases were negative for Cerb-B2. No difference in antigen expression was seen in the epithelial versus sarcomatous components. Primary and recurrent tumors were concordant for p53, P-cadherin, and Cerb-B2. However, three cases of recurrent tumors were negative for p16 expression. P53, p16, and P-cadherin are common tumor suppressor genes expressed in uterine MMMT. Interestingly, p16 protein expression was lost in some cases of MMMTs when they recurred. This suggests that the oncoprotein and possibly genetic profile of p16 changes over time. We did not observe any difference in antigen expression between areas of epithelial or sarcomatous differentiation, which would support a single pluripotential malignant clone in the histogenesis of these tumors.