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


METHODS
23 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.


RESULTS
Histopathological 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.


CONCLUSIONS
Our 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.
Kanthan
Rani
R
Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, SK, Canada. rani.kanthan@saskatoonhealthregion.ca
Senger
Jenna-Lynn B
JL
Diudea
Dana
D
D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D018200:Mixed Tumor, Mullerian / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins