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.

Uterine Carcinosarcomas (Malignant Mixed Müllerian Tumours): A Review with Special Emphasis on the Controversies in Management

“…5-year survival rates in early uterine carcinosarcomas (FIGO Stages I/II) are between 30%–46%, and 0%–10% in advanced cancers (FIGO Stages III/IV) [19]. The median survival in patients with uterine carcinosarcoma ranges between 16 and 40 months [11] with death usually occurring within 1-2 years of the initial diagnosis [71]. The prognosis of uterine carcinosarcoma is worse than that of endometrial carcinoma with adjustment for known adverse prognostic factors [25, 72].…”

“…Tumour characteristics of molecular markers such as expression of p53 in older women are associated with a shorter mean survival, while p53 negative tumours occurring in younger women have a longer survival [24, 38]. Immunohistochemical tumour expression of other cell cycle and apoptotic regulatory proteins such as p16 and Mcl-1 are also associated with longer survivals [24, 38, 71]. Trends observed in such individual series are difficult to generalize due to small sample sizes and need to be validated as predictive and/or prognostic markers with further research in larger tumour populations.…”

Malignant mixed Mullerian tumors of the uterus: histopathological evaluation of cell cycle and apoptotic regulatory proteins

“…Malignant mixed Mullerian tumors (MMMT) of the uterus are rare, high-grade neoplasms comprising only 1-2% of uterine cancers [1] and 3-5% of all uterine malignancies [2]. They are the most common variety of mixed epithelial and non-epithelial endometrial tumors, with a clinically aggressive course [3,4].…”

F-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in a Rare Case of Recurrent Malignant Mixed Mullerian Tumor

“…[1] They occur in postmenopausal women and comprise only 1-2% of uterine cancers and 3-5% of all uterine malignancies. [2] Clinical presentation usually consists of abdominal pain, distension, and atypical bleeding. Though common in the uterus, these tumors may also arise in the ovaries, fallopian tubes and vagina.…”

“…Though common in the uterus, these tumors may also arise in the ovaries, fallopian tubes and vagina. [12345] MMMT is composed of both epithelial (carcinoma) and mesenchymal (sarcoma) elements but the component responsible for its aggressive biological behavior remains unclear. [67] Survival rates for Stages I-III are dismal ranging from 33% to 39%, respectively.…”