Abstract
AimThe aim of our study was to evaluate survival outcomes in malignant mixed Mullerian tumors (MMMT) of the uterus with respect to the role of cell cycle and apoptotic regulatory proteins in the carcinomatous and sarcomatous components.Methods23 cases of uterine MMMT identified from the Saskatchewan Cancer Agency (1970-1999) were evaluated. Immunohistochemical expression of Bad, Mcl-1, bcl-x, bak, mdm2, bax, p16, p21, p53, p27, EMA, Bcl-2, Ki67 and PCNA was correlated with clinico-pathological data including survival outcomes.ResultsHistopathological examination confirmed malignant epithelial component with homologous (12 cases) and heterologous (11 cases) sarcomatous elements. P53 was strongly expressed (70-95%) in 15 cases and negative in 5 cases. The average survival in the p53+ve cases was 3.56 years as opposed to 8.94 years in p53-ve cases. Overexpression of p16 and Mcl-1 were observed in patients with longer survival outcomes (> 2 years). P16 and p21 were overexpressed in the carcinomatous and sarcomatous elements respectively. Cyclin-D1 was focally expressed only in the carcinomatous elements.ConclusionsOur study supports that a) cell cycle and apoptotic regulatory protein dysregulation is an important pathway for tumorigenesis and b) p53 is an important immunoprognostic marker in MMMT of the uterus.
Highlights
Malignant mixed Mullerian tumors (MMMT) of the uterus are rare, high-grade neoplasms comprising only 12% of uterine cancers [1] and 3-5% of all uterine malignancies [2]
The aim of this study is to evaluate the role of cell cycle and apoptotic regulatory proteins in the carcinomatous and sarcomatous components of uterine MMMT in relation to clinicopathological data including survival outcomes
Our study supports that cell cycle and apoptotic regulatory protein dysregulation is an important pathway for tumorigenesis
Summary
Malignant mixed Mullerian tumors (MMMT) of the uterus are rare, high-grade neoplasms comprising only 12% 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]. Stage of the disease and the depth of myometrial invasion are recognized as important prognostic factors [5,6,7]. This tumor may arise in the ovaries, fallopian tubes and vagina [5,9]. MMMT is a biphasic tumor composed of both epithelial (carcinoma) elements and mesenchymal (sarcoma) ele-
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