[1200] Tissue Array Analysis of Apoptotic and Cell Cycle Regulatory Markers in Benign and Malignant Uterine Smooth Muscle Tumours: A Clinicopathologic Study of 52 Cases

P Vasudev, M Farag, C Salib, D Browning, W Foster, O Boutross-Tadross. McMaster University, Hamilton, Canada

Background: This study was undertaken to investigate the expression of apoptotic and cell cycle regulatory markers in uterine smooth muscle tumors (USMTs), in order to evaluate the utility of immunohistochemistry in differentiating benign from malignant tumors, and to identify signalling pathways underlying the development of leiomyosarcoma (LMS).
Design: Fifty two cases of USMTs including LMS (n=15), undetermined malignant potential (STUMP, n=4), leiomyoma variants (LV, n=14) and benign leiomyomas (BL, n=19) were reviewed light microscopically to measure apoptotic count. Tissue arrays were created with 2 representative cores from each case. Immunohistochemical staining was performed for bcl-2, Ki-67, p53 and p16 and each case was given a value of 0% to 100% positive cells. Comparison of numerical data was performed by the Kruskal-Wallis test. Findings were correlated with pathological and clinical parameters.
Results: The mean apoptotic count was significantly higher in LMS (13/10HPF) compared to BL (<1/10HPF) (p<0.001). While the mean percentage expression of p53 (22 % vs. <1%; p=0.017), p16 (46 % vs. 2 %; p=0.002) and Ki-67 (22 % vs. 3%; p=0.001) was significantly higher in LMS than in BL; the bcl-2 expression (71 % vs. 81%; p=0.48) was not significantly different.

Table 1 : Comparative expression of cell cycle and apoptotic markers.
MarkerLMSSTUMPLVBLp-value*
P53(%)22 (0-80)22 (0-80)9 (0-30)1 (0-10)0.017
P16(%)46 (0-100)10 (0-40)3 (0-20)2 (0-20)0.002
Bcl-2(%)71 (0-100)88 (50-100)95 (70-100)81 (40-100)0.48
Apoptosis (/10HPF)13 (1-36)4 (1-8)2 (1-4)<1 (0-1)<0.001
Ki67(%)22 (0-60)14 (0-40)4 (0-20)3 (0-25)0.001
Results are expressed as mean (range). *p-value vs. LMS and BL.


Conclusions: The significantly higher apoptotic count in LMS combined with lack of significantly lower expression of bcl2 suggests that other anti/pro-apoptotic proteins may be involved in increased apoptosis in LMS. p16 positivity was found to be the most useful marker for LMS showing both nuclear and cytoplasmic positivity in up to 100% of cells. The differential expression of p53 and p16 indicates that these proteins may have a role in the pathogenesis of LMS.
Category: Gynecologic & Obstetrics

Wednesday, March 24, 2010 9:30 AM

Poster Session V # 148, Wednesday Morning

 

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