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

Kanthan R, Senger JL, Diudea D - World J Surg Oncol (2010)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, SK, Canada. rani.kanthan@saskatoonhealthregion.ca

ABSTRACT

Aim: 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.

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Related in: MedlinePlus

Demographic and Clinical Data in Relation to 2 Year Survival Data. X-axis displays: age, postmenopausal bleeding, homologous elements, stage III/IV, depth of invasion, and metastasis. Y-axis displays: survival outcome data-including overall survival (purple bars), two-year survival (maroon bars), and less than two-year survival (yellow bars). * p < 0.05 based on Fisher's Exact Test.
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Figure 2: Demographic and Clinical Data in Relation to 2 Year Survival Data. X-axis displays: age, postmenopausal bleeding, homologous elements, stage III/IV, depth of invasion, and metastasis. Y-axis displays: survival outcome data-including overall survival (purple bars), two-year survival (maroon bars), and less than two-year survival (yellow bars). * p < 0.05 based on Fisher's Exact Test.

Mentions: Table 2 and Figure 2 list the various demographic and clinico-pathological data of 23 patients with uterine MMMT. The majority of patients (39.1%) were 71-80 years old, followed by 61-70 years (26.1%). 18 patients (78.3%) presented with postmenopausal bleeding. Histologically, 11 patients (47.8%) had homologous elements, while 10 (43.5%) had heterologous elements. 10 patients (43.5%) were Stage I, two (8.7%) Stage II, three (13.0%) Stage III and seven (30.4%) Stage IV. Myometrial depth of invasion was superficial in 43.5% of patients, and deep in 30.4%. Metastases were present in 43.5% of patients at presentation in the liver, ovaries, fallopian tube, abdomen, peritoneum, ommentum, bladder, and iliac lymph nodes. Five cases (21.7%) exhibited pelvic metastasis. Lung and cervical metastasis were present in 2 patients (8.7%). Management protocols included surgery (20 patients, 87.0%), chemotherapy, (2 patients, 8.7%) and radiation therapy (14 patients, 60.9%).


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

Kanthan R, Senger JL, Diudea D - World J Surg Oncol (2010)

Demographic and Clinical Data in Relation to 2 Year Survival Data. X-axis displays: age, postmenopausal bleeding, homologous elements, stage III/IV, depth of invasion, and metastasis. Y-axis displays: survival outcome data-including overall survival (purple bars), two-year survival (maroon bars), and less than two-year survival (yellow bars). * p < 0.05 based on Fisher's Exact Test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2913917&req=5

Figure 2: Demographic and Clinical Data in Relation to 2 Year Survival Data. X-axis displays: age, postmenopausal bleeding, homologous elements, stage III/IV, depth of invasion, and metastasis. Y-axis displays: survival outcome data-including overall survival (purple bars), two-year survival (maroon bars), and less than two-year survival (yellow bars). * p < 0.05 based on Fisher's Exact Test.
Mentions: Table 2 and Figure 2 list the various demographic and clinico-pathological data of 23 patients with uterine MMMT. The majority of patients (39.1%) were 71-80 years old, followed by 61-70 years (26.1%). 18 patients (78.3%) presented with postmenopausal bleeding. Histologically, 11 patients (47.8%) had homologous elements, while 10 (43.5%) had heterologous elements. 10 patients (43.5%) were Stage I, two (8.7%) Stage II, three (13.0%) Stage III and seven (30.4%) Stage IV. Myometrial depth of invasion was superficial in 43.5% of patients, and deep in 30.4%. Metastases were present in 43.5% of patients at presentation in the liver, ovaries, fallopian tube, abdomen, peritoneum, ommentum, bladder, and iliac lymph nodes. Five cases (21.7%) exhibited pelvic metastasis. Lung and cervical metastasis were present in 2 patients (8.7%). Management protocols included surgery (20 patients, 87.0%), chemotherapy, (2 patients, 8.7%) and radiation therapy (14 patients, 60.9%).

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, SK, Canada. rani.kanthan@saskatoonhealthregion.ca

ABSTRACT

Aim: 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.

Show MeSH
Related in: MedlinePlus