Proliferation, ploidy and prognosis in uterine smooth muscle tumours

Abstract

DNA ploidy, mitotic rate (per 10 high power fields), mitotic index (per 1000 tumour nuclei), Ki-67 labelling index and S phase fraction were measured in 23 uterine leiomyosarcomas and 10 tumours of uncertain malignant potential. Correlations were calculated by Spearmann rank correlation. Univariate survival analysis was performed by log rank analysis and multivariate analysis performed by the Cox linear regression method. Ki-67 index and S phase fraction were significantly higher in leiomyosarcomas than in tumours of uncertain malignant potential. There was significant correlation between mitotic rate, mitotic index, Ki-67 index and S phase fraction in cases of leiomyosarcoma. Fifteen of 22 leiomyosarcomas and one of 10 tumours of uncertain malignant potential were DNA aneuploid. On univariate analysis of all the smooth muscle tumours, DNA ploidy, presence of significant nuclear atypia and presence of coagulative tumour cell necrosis were associated with outcome. Only DNA ploidy was associated with outcome in the group of leiomyosarcomas. On multivariate analysis of all of the smooth muscle tumours, DNA ploidy, age and grade of atypia were independently associated with outcome. No single factor was independently predictive of outcome in the group of leiomyosarcomas. Alternative indices of cell proliferation correlate with mitotic rate in uterine leiomyosarcoma and do not provide additional useful prognostic information. DNA ploidy, age and grade of atypia are independently associated with outcome in uterine smooth muscle tumours and measurement of DNA ploidy may be useful in identification of cases with an adverse prognosis.

Clinicopathologic markers of uterine leiomyosarcoma originating from smooth muscle tumors of low malignancy

“…However, none of the tests revealed a difference between both groups, and we were unable to identify a single prognostic marker. From clinical point of view, previous studies demonstrated that the average age of LMS (54-58 years) is higher when compared to SMTLM (46 year) [2,13]. However, the current observation that older women with SMTLM are more likely to recur when compared to younger women was not reported before.…”

“…Table 3 Summary of immunohistochemical stainings on tumors that did not relapse (1,2,3), primary tumors that did relapse (4,5), and their recurrences (4R, 5R) The cell cycle drives cellular division and is regulated by several important protein families. Two main pathways in a cell cycle can be discerned: the p53 pathway, regulated by p53, MDM2, and p21(WAF); and the retinoblastomacyclin D pathway, controlled by Rb, p16, and cyclin D. Cyclins are a group of proteins periodically expressed during the cell cycle, which form complexes with cyclindependent kinases (cdk).…”

“…In LMS, different chromosomal abnormalities are described, among these are chromosome 1 instability (loss on p-arm, gain on q-arm), monosomy 6, alterations in p53, t(10-17),..., but the specificity and the significance of these alterations in the tumorigenesis have still to be assayed [11,12]. Although 15-20% of SMTLM relapse [2,4,9,13,14], we are currently unable to identify patients at risk.…”

“…The low prevalence of SMTLM, previously called STUMP (smooth muscle tumor of unknown malignant potential), adds to a paucity of data on a molecular level that have been reported. Studies on various ancillary techniques to improve diagnostic accuracy and to predict the clinical behavior of uterine smooth muscle tumors suggested possible roles for estrogen receptor (ER), progesterone receptor (PR), α-SMA and WT-1 expression, and proliferation makers including Ki-67, p53, p16, p21, Rb, cyclin A, cyclin E and cyclin D, and vascular endothelial growth factor (VEGF) [2][3][4][5][6][7][8][9][10]. Malignant transformation generally is believed to be associated with changes in expression of a number of genes.…”

Analysis of Allelic Loss as an Adjuvant Tool in Evaluation of Malignancy in Uterine Smooth Muscle Tumors

“…33 Despite some worrisome histologic findings and the overall uncertain prognosis in STUMPs, the few published studies that reported outcome in these patients indicate that the majority are clinically benign. 14,22 Nevertheless, the unpredictable behavior of STUMPs makes clinical management of patients difficult, especially when the diagnosis is made on a myomectomy specimen in a woman who wants to preserve her uterus.…”