Estrogen and progesterone receptor expression in patients with uterine smooth muscle tumors

OBJECTIVE: To investigate the expression of estrogen and progesterone receptor in uterine leiomyomas, smooth muscle tumors of uncertain malignant potential (STUMP), and leiomyosarcomas (LMS), and to assess the correlation between steroid receptor expression and clinicopathologic parameters in LMS. DESIGN: Estrogen/progesterone receptor expression was investigated by immunohistochemistry. SETTING: Department of Gynecology and Obstetrics of the University Hospital of Vienna. PATIENT(S): Twenty-six women with leiomyoma, 24 with STUMP, and 21 with LMS of the uterus. INTERVENTION(S): Formalin-fixed, paraffin-embedded tissues were sectioned and stained. MAIN OUTCOME MEASURE(S): Number of tumor cells stained. RESULT(S): Significant differences regarding the frequency of estrogen receptor expression were observed between LMS and leiomyoma and STUMP and leiomyoma (P<.05). The progesterone receptor expression did significantly differ between LMS and STUMP (P=.05), and LMS and leiomyoma (P<.05). In uterine LMS, the relationship between estrogen/progesterone receptor expression and clinicopathologic parameters did not reach statistical significance (P>.05), and neither of the markers studied revealed prognostic significance (P>.05). CONCLUSION(S): The present study observed significant differences of steroid receptor expression between uterine leiomyoma, STUMP, and LMS. Our data indicate that the progesterone receptor may be an especially useful marker to distinguish cases of malignant smooth muscle tumors in which histological features are ambiguous or borderline.     

Expression of matrix metalloproteinases in patients with uterine smooth muscle tumors: an immunohistochemical analysis of MMP-1 and MMP-2 protein expression in leiomyoma, uterine smooth muscle tumor of uncertain malignant potential, and leiomyosarcoma

OBJECTIVE: Matrix metalloproteinases (MMPs) have been suggested to play an important role in tumor invasion and metastasis. We compared the expression of MMP-1 and MMP-2 protein in patients with leiomyoma, uterine smooth muscle tumor of uncertain malignant potential (STUMP), and leiomyosarcoma (LMS). METHODS: MMP-1 and MMP-2 expression was investigated by immunohistochemistry from paraffin-embedded tissue in 26 patients with leiomyoma, in 24 patients with STUMP, and in 21 patients with LMS. RESULTS: MMP-1 was expressed in 92% of leiomyomas, in 83% of STUMP, and in 86% of LMS, whereas MMP-2 was expressed in 12% of leiomyomas, in 17% of STUMP, and in 48% of LMS. A statistically significant difference regarding the frequency of MMP-2 expression was observed between LMS and STUMP (P =.025) as well as between LMS and leiomyoma (P =.006), but not between STUMP and leiomyoma (P >.05). Likewise, the staining intensity did significantly differ between LMS and leiomyoma (P =.025), but no statistical significant difference was observed between LMS and STUMP (P >.05) and between STUMP and leiomyoma (P >.05). CONCLUSION: The stronger MMP-2 expression in patients with LMS compared with STUMP and leiomyoma indicates that this protein might be a marker for tumor invasion or metastasis in patients with uterine LMS. Furthermore, MMP-2 seems to be a useful immunohistochemical parameter to distinguish cases of smooth muscle tumors in which histologic features are ambiguous or borderline. Further studies including larger numbers of patients are necessary to establish MMP-2 as a routine marker for tumor invasion and progression.     

Ki-67 expression in patients with uterine leiomyomas, uterine smooth muscle tumors of uncertain malignant potential (STUMP) and uterine leiomyosarcomas (LMS)

BACKGROUND: The aim of the current study was to evaluate the expression of Ki-67 in uterine smooth muscle tumors, comparing leiomyomas, uterine smooth muscle tumors of uncertain malignant potential (STUMP) and uterine leiomyosarcomas (LMS) and to prove the accuracy of a Ki-67 expression as a useful parameter in the diagnosis of LMS. METHODS: Ki-67 was assessed using immunohistochemistry from paraffin-embedded tissue in 20 patients with uterine LMS, 22 cases of STUMP and 25 cases of leiomyomas. RESULTS: Ki-67 was present in 10/20 (50%) LMS, in 0/22 (0%) STUMP and in 2/25 (8%) leiomyomas. Significant differences regarding the frequency of Ki-67 expression were observed between LMS and STUMP (p = 0.0001) as well as between LMS and leiomyomas (p = 0.002), but not between STUMP and leiomyomas (p = 0.491). Likewise, the staining intensity differed significantly between LMS and leiomyomas (p = 0.018) as well as between LMS and STUMP (p = 0.002), but not between STUMP and leiomyomas (p = 0.368). CONCLUSIONS: Our results demonstrate that the significantly elevated Ki-67 antigen expression in LMS, which correlates well with the rapid growth of these malignant tumors, may be a useful immunohistochemical parameter to distinguish between cases of malignant smooth muscle tumors and those of uncertain or borderline histology.     

Expression of p16 protein in patients with uterine smooth muscle tumors: an immunohistochemical analysis

OBJECTIVE: The loss of cell cycle control is a critical step in the development of neoplasia. The p16 protein has been identified as a tumor suppressor protein, which binds specifically to the cyclin-dependent kinase CDK-4, inhibiting the catalytic activity of the CDK4-cyclin D complex, and thereby acts as a negative cell cycle regulator. In the present study, we compared the expression of p16 protein in cases with leiomyoma, uterine smooth muscle tumor of uncertain malignant potential (STUMP), and leiomyosarcoma (LMS). METHODS: P16 expression was investigated by immunohistochemistry from paraffin-embedded tissue in 26 patients with leiomyoma, in 24 patients with STUMP, and in 21 patients with LMS. RESULTS: P16 was expressed in 12% of leiomyomas, in 21% of STUMP, and in 57% of LMS. A statistically significant difference regarding the frequency of p16 protein expression was observed between LMS and STUMP (P < 0.05) as well as between LMS and leiomyoma (P < 0.05), but not between STUMP and leiomyoma (P > 0.05). Likewise, the staining intensity did significantly differ between LMS and leiomyoma and between LMS and STUMP (P < 0.05), but no statistical significant difference was observed between STUMP and leiomyoma (P > 0.05). No statistically significant correlation between p16 expression and clinical stage, age, vascular space involvement, and recurrence disease could be found in patients with LMS (P > 0.05). Additionally, the overall survival did not significantly differ between p16-positive and p16-negative cases (P > 0.05). CONCLUSIONS: We found that p16 was more frequently and more strongly expressed in LMS compared to STUMP and leiomyoma. We therefore concluded that p16 might play an important role in sarcomagenesis. Furthermore, p16 might be a useful immunohistochemical marker, which could help to distinguish cases of smooth muscle tumors in which histologic features are ambiguous or borderline, but the use of p16 in a diagnostic setting should await further clinical studies and clarification of the mechanisms.     

Expression of thrombospondin 1 (TSP 1) in patients with uterine smooth muscle tumors: an immunohistochemical study

OBJECTIVE: Angiogenesis is an essential component for tumor development regulated by both proangiogenic and antiangiogenic factors. Thrombospondin 1 (TSP 1) suppresses angiogenesis by inhibiting endothelial cell proliferation and inducing endothelial cell apoptosis. The aim of this study was to compare the expression of TSP 1 in cases with leiomyoma, uterine smooth muscle tumor of uncertain malignant potential (STUMP) and leiomyosarcoma (LMS). Furthermore, we evaluated the prognostic relevance of TSP 1 in uterine LMS. METHODS: TSP 1 expression was investigated by immunohistochemistry from paraffin-embedded tissue in 26 patients with leiomyoma, in 24 patients with STUMP and in 21 patients with LMS. Standard immunohistochemical techniques were used to study the expression of TSP 1 in 5-mum-thick tumor sections. TSP 1 expression was correlated with survival using the Kaplan-Meier method and log-rank test for univariate analysis. RESULTS: TSP 1 was expressed in 77% of leiomyomas, in 13% of STUMP and in 24% of LMS. A statistically significant difference regarding the frequency of TSP 1 expression was observed between leiomyoma and LMS (P < 0.05) as well as between leiomyoma and STUMP (P < 0.05), but not between LMS and STUMP (P > 0.05). Furthermore, a statistically significant correlation between vascular space involvement and TSP 1 expression was observed in patients with uterine LMS, with patients without vascular space involvement having more frequently TSP 1 positive tumors (P = 0.04). No statistically significant correlation between TSP 1 and clinical stage, age and recurrence disease could be detected (P > 0.05). CONCLUSIONS: We found that TSP 1 was more frequently expressed in leiomyoma compared to STUMP and LMS. Additionally, the statistically significant negative correlation between vascular space involvement and TSP 1 expression in patients with uterine LMS shows that TSP 1 might work as a predictive factor in patients with LMS. Further clinical studies are necessary to prove our results and to clarify the role of TSP 1 in uterine smooth muscle tumors.     

Diagnostic criteria for uterine smooth muscle tumors: leiomyoma variants associated with malignant behavior

OBJECTIVE: To determine the prognostic accuracy of current diagnostic criteria for uterine smooth muscle tumors. STUDY DESIGN: Cases of uterine leiomyosarcoma (LMS) treated from 1976 to 1999 were analyzed retrospectively. Uterine LMS specimens were reevaluated using current criteria by a pathologist specializing in gynecologic diseases. Kaplan-Meier survival curves were evaluated. RESULTS: Specimens were available from 67 patients diagnosed with uterine LMS. On rereview, only 47 specimens were thought to represent uterine LMS. The 20 other patients were deemed to have leiomyomas or leiomyoma variants, including 13 cellular leiomyomas, 5 atypical leiomyomas and 2 leiomyomas. Median survival for patients with uterine LMS was 2.1 years. (Ninety-seven percent of disease-specific deaths occurred within 6 years after the diagnosis.) With leiomyoma variants, median survival was > 25 years. Among these 18 women were 3 disease-specific deaths (all > 6 years after diagnosis). CONCLUSION: Diagnostic criteria for uterine smooth muscle tumors require continued refinement. A small but significant number of patients diagnosed with leiomyoma variants will die of the disease. In contrast to the aggressive behavior of uterine LMS, disease-specific deaths attributed to leiomyoma variants occurred later. With this potential for delayed recurrence, these patients warrant close clinical surveillance.     

p21~(WAF1/CIP1)和P53蛋白在子宫平滑肌肿瘤的表达和意义

目的 :探讨p2 1WAF1/CIP1和P5 3蛋白在子宫平滑肌肿瘤 (USMTs)的表达和意义。方法 :应用免疫组织化学法检测 2 0例普通型子宫平滑肌瘤 (UL) ,18例子宫平滑肌肉瘤 (LMS)及 70例交界性子宫平滑肌瘤 (BLM) :包括 4 0例富于细胞型子宫平滑肌瘤 (CL)、13例奇异型子宫平滑肌瘤 (BL)、4例核分裂活跃型子宫平滑肌瘤 (ML)、10例不典型子宫平滑肌瘤 (AL)及 3例恶性潜能未定型子宫平滑肌瘤 (STUMP)的p2 1WAF1/CIP1和P5 3蛋白的表达。结果 :LMS组p2 1WAF1/CIP1蛋白表达阳性率明显高于UL组 (P <0 .0 1)和BLM组 (P<0 .0 1) ;LMS组P5 3蛋白表达阳性率显著高于UL组 (P <0 .0 1)和BLM组 (P <0 .0 1)。结论 :LMS的发病机制涉及P5 3基因功能的丧失 ;p2 1WAF1/CIP1在USMT细胞的增殖和灭活中可能起到不同的作用     

Apoptotic and cell cycle regulatory markers in uterine leiomyosarcoma

OBJECTIVES: The primary aim of this study was to investigate the expression of apoptotic and cell cycle regulators p53, p21, p27, bax, and bcl-2 in uterine leiomyosarcoma in order to identify molecular pathways that possibly could be important in the development of leiomyosarcoma. A secondary aim was to examine if the apoptotic and cell cycle regulatory protein expression profile of uterine leiomyosarcoma is potentially useful for clinical prognostic purposes. METHODS: A tissue microarray representing 36 uterine leiomyosarcomas and 19 uterine leiomyomas was created with 3 representative cores from each tumor. Immunohistochemical staining was performed for bcl-2, bax, p21, p27, and p53 using standard techniques. Staining was scored 0-12 for each marker, 0-3 being negative and 4-12 positive. Outcome analyses were performed only for leiomyosarcomas. First recurrence was determined from the time of initial diagnosis. Survival was determined from the time of initial diagnosis to last follow-up. RESULTS: Associations were found between disease type (leiomyosarcoma vs. leiomyoma) and the positivity status of p21 (43% vs. 0%, P < 0.001), p53 (54% vs. 0%, P < 0.001), and bax (34% vs. 94%, P < 0.001). bcl-2-positive leiomyosarcoma was associated with a longer time to recurrence (P = 0.02) in a univariate analysis. In a multivariate analysis, tumor stage was the only independent significant prognostic factor (P = 0.002). CONCLUSION: The significant differential expression of apoptotic and cell cycle regulatory proteins in uterine leiomyosarcoma as compared to benign smooth muscle tumors suggests that pathways involving these proteins may be important in the development of malignant disease and, therefore, could be potential targets for molecular therapies.     

MMP-1 and MMP-2 expression in uterine leiomyosarcoma and correlation with different clinicopathologic parameters

OBJECTIVE: Matrix metalloproteinases (MMPs) have been suggested to play an important role in tumor invasion and metastasis because they degrade a wide range of components of the extracellular matrix. In the present study, we analyzed the expression of MMP-1 and MMP-2 proteins in patients with uterine leiomyosarcoma. METHODS: MMP-1 and MMP-2 expression was investigated by immunohistochemistry from paraffin-embedded tissue sections in 21 patients with uterine leiomyosarcoma (LMS). The immunohistochemical findings were correlated with different clinicopathologic characteristics of the patients. RESULTS: MMP-1 was expressed in 86% and MMP-2 was expressed in 48% of uterine LMS. There was a statistically significant positive correlation between vascular space involvement and MMP-2 expression (P =.05) and between age and MMP-2 expression, with patients over 50 years old having significantly more frequent MMP-2-positive tumors than patients younger than 50 years (P =.006). The relationship between MMP-2 expression and tumor stage and recurrence disease did not reach statistical significance. A trend towards prolonged disease-free survival was observed in women with MMP-2-negative LMS compared with patients with MMP-2-positive LMS (P =.09). Furthermore, a univariate analysis revealed that early tumor stage (P =.0001), age at diagnosis less than 50 years (P =.02), and the absence of vascular space involvement (P =.04) were associated with longer overall survival. CONCLUSION: The statistically significant positive correlation between MMP-2 expression and vascular space involvement as well as the prolonged disease-free survival rate in patients with MMP-2 negative uterine LMS suggest that MMP-2 plays an important role in tumor invasion and metastasis. Further clinical studies with larger numbers of cases need to be performed to verify these findings.     

Differential expression of P16 and P21 in benign and malignant uterine smooth muscle tumors

Purpose  

The diagnosis of benign and malignant uterine smooth muscle tumors depends on morphologic criteria such as nuclear atypia, coagulative tumor cell necrosis and mitotic activity. Most of these tumors are readily classifiable into benign or malignant categories using these criteria. However, the distinction between leiomyomas and leiomyosarcomas may at times be problematic. Hence, it would be useful to have additional markers which could help to distinguish these tumors. The aim of the study was to evaluate p16 and p21 expressions in uterine smooth muscle tumors and determine whether p16 and p21 have a potential value in the differential diagnosis of problematic cases. In addition, we evaluated whether the differential expression of p16 and p21 in uterine leiomyosarcomas correlated with tumor recurrence and patient survival.     

Unexpected uterine smooth muscle tumor of uncertain malignant potential and sarcoma: A single center cohort study in South Korea

ObjectiveTo evaluate the risk of encountering unexpected uterine smooth muscle tumors of uncertain malignant potential (STUMPs) or sarcomas during surgical treatment of mesenchymal tumors of the uterus using morcellation.Material and methodsData were collected retrospectively from subjects who were pathologically diagnosed with uterine leiomyoma or its variants, STUMP or other premalignant mesenchymal tumors of uterus, or sarcoma during surgical treatment between July 2014 and June 2017.ResultsA total of 3785 women were investigated; 2824 laparoscopic procedures (74.6%) were performed, and an electronic power morcellator was used in 1636 patients (43.2%). Sixteen women (0.42%) were diagnosed with STUMP and 14 (0.37%) were diagnosed with uterine sarcoma. The incidence rate of unexpected STUMP or uterine sarcoma was 0.61% (23 of 3785 women); unexpected STUMP in 13 (0.34%), and unexpected sarcoma was in 10 (0.26%). Moreover, the unexpected leiomyosarcoma rate was 0.08% (3 in 3785). The rate of unintended morcellation of STUMPs was relatively high at 0.26% (10 in 3785), however, that for uterine sarcomas was 0.05% (2 in 3785).ConclusionThe risks of unintended morcellation were very low for sarcomas and STUMPs, although the risk of the latter was approximately 5-fold that of the former. To reduce the unintended dissemination of tumors, patients suspected of having malignancies should be provided adequate information regarding their treatment options as well as their associated risks. Meanwhile, improved preoperative screening methods for STUMP and sarcoma should be established.     

Expression of chemokines CCL5 and CCL11 by smooth muscle tumor cells of the uterus and its possible role in the recruitment of mast cells

OBJECTIVE: Smooth muscle tumors of uterus have been reported to contain considerable number of mast cells, especially cellular leiomyoma. However, to our knowledge the mechanism by which mast cells increased in them is not known. The purpose of this study was to reveal the different mast cell subsets in smooth muscle tumors of uterus and to investigate the mechanism of local increase of mast cells. METHODS: Tissue sections from 85 uterine smooth muscle tumors were studied using immunohistochemical double labeling techniques, including 40 cases of ordinary leiomyomas, 30 cases of cellular leiomyomas and 15 cases of leiomyosarcomas. The sections were double immunostained for mast cell tryptase and chymase, mast cell tryptase and ki-67, mast cell tryptase and chemokines (i.e., CCL2, CCL5, CCL11, TGFbeta), as well as tryptase and CCR3. RESULTS: MC(TC)-type of mast cells was the predominant type in ordinary leiomyoma and cellular leiomyoma, whereas MC(T)-type was seldom found in them. There was no MC(C) in smooth muscle tumors. The total intratumoral number of mast cells in cellular leiomyoma group was significantly higher than that in both leiomyosarcoma and ordinary leiomyoma (P<0.01). Mast cells proliferation was rarely detected in smooth muscle tumors, as revealed by constant negative labeling of the proliferation marker Ki-67 in mast cells. Almost all mast cells (tryptase positive) in smooth muscle tumors were also CCL2, CCL5, CCL11 and TGFbeta positive. Expressions of CCL5 and CCL11 in tumor cells in cellular leiomyoma were all significantly higher than that in both ordinary leiomyoma and leiomyosarcoma (P<0.01). While the expression of TGFbeta in tumor cells in cellular leiomyoma was not significantly different from that in ordinary leiomyoma, expression of CCL2 was not observed in smooth muscle tumor cells. There were positive correlations between CCL5 and the number of mast cells (r(s)=0.801, P<0.01) and between CCL11 and the number of mast cells (r(s)=0.744, P<0.01) in smooth muscle tumors as well. The vast majority of the mast cells in cellular leiomyoma were CCR3 positive. CONCLUSIONS: Using the monoclonal anti-mast cell tryptase antibody could detect all mast cells in smooth muscle tumor. The increased intratumoral mast cell counts in cellular leiomyoma might be the result of mast cells recruitment from the peripheral blood rather than local mast cells proliferation. CCL5 and CCL11, which are expressed by smooth muscle tumor cells, are possibly responsible for the recruitment of mast cells in uterine cellular leiomyoma. Whether they combine to CCR3 expressed by mast cells need further study.     

A retrospective analysis of the clinicopathologic characteristics of uterine cellular leiomyomas in China

ObjectiveTo investigate the clinicopathologic features of uterine cellular leiomyomas (CLs) by comparing them with those of uterine leiomyosarcomas (LMSs).MethodsA case–control study comparing 78 cases of CL with 10 cases of LMS was conducted. The patients’ records were reviewed to abstract information on tumors features and treatment, immunohistochemical findings, and disease prognosis.ResultsThe mean age at diagnosis was 45.3 ± 8.41 years in the CL group. The main clinical CL manifestations were menstrual abnormalities (56.4%), abdominal pain or distension (14.1%), and pelvic pressure (8.9%). Abdominal pain or distension was significantly more common in the LMS than in the CL group (P < 0.05). Generally, CL tumors were smaller in diameter than LMS tumors (P < 0.05). Moreover, lower levels of Ki-67 and PCNA expression were measured in CL than in LMS tumors (P < 0.05). There were no cases of malignant transformation or metastasis in 41 patients with CL who adhered to long-tern follow-up.ConclusionNo symptoms were found to be specifically associated with CL, and management of CL does not need to differ from that of ordinary leiomyoma. In contrast to malignant disease, CL has a favorable long-term prognosis. However, given its “borderline” pathologic nature, patients with CL require clinical surveillance.     

Immunohistochemical analysis of p16 expression in uterine smooth muscle tumors

The expression of p16 as a tumor suppressor protein was evaluated in a retrospective analysis of paraffin-embedded tissue specimens of leiomyosarcoma (LMS), leiomyoma (LM) and normal myometrium. In this study, we investigated by immunohistochemistry p16 expression in 15 LMSs, 15 LMs and ten normal myometrium. Strong expression of p16 was found in 12 of the 15 LMSs and in three cases weak expression; three LMs had focal and weak p16 staining but none of the normal myometrium. A statistically significant difference regarding the frequency of p16 protein expression was observed between LMS and LM (p: 0.0001). We concluded that the results of this study confirm the overexpression of p16 in LMS. Therefore, the present study suggests that p16 might be a useful immunohistochemical marker which could help in distinguishing uterine LMS from LM and its benign variants.     

A comparative study of the effect of raloxifene and gosereline on uterine leiomyoma volume changes and estrogen receptor, progesterone receptor, bcl-2 and p53 expression immunohistochemically in premenopausal women

OBJECTIVE: To compare the mechanism of action of raloxifene and gosereline induced shrinkage of leiomyomas via estrogen receptor, progesterone receptor, bcl-2 and p53 expression immunohistochemically. STUDY DESIGN: Thirty-two premenopausal women affected by uterine leiomyomas were randomized into two equal groups. Group A was treated with gosereline (3.6 mg subcutaneous injection monthly) and group B was treated with raloxifene (60 mg daily per os) for 3 months before undergoing surgery. At entry and at the end of the treatment the leiomyoma volume was measured ultrasonografically and the volume change was calculated. Immunohistochemical detection of estrogen receptor (ER), progesterone receptor (PR), bcl-2 and p53 were performed on leiomyoma tissue samples from group A, group B and the matched-control group. H-scores for ER, PR, bcl-2 and p53 were calculated. The mean volume changes of leiomyomas and immunohistochemical H-score differences of ER, PR, bcl-2 and p53 were compared between groups. RESULTS: The leiomyoma volume decreased significantly after treatment in gosereline group from baseline of 65 cm(3) to 35 cm(3), and in raloxifene group from 68 cm(3) to 50 cm(3), p<0.05. The difference between the before and after treatment leiomyoma volumes between the two treatments was not statistically significant. H-score of ER expression was significantly lower in gosereline group compared to control group (54.4 versus 113.2, p = 0.001), whereas H-score of PR expression was significantly lower with both gosereline and raloxifene groups compared to control group (64.8 for gosereline versus 94.6 for control, 73.6 for raloxifene versus 94.6 for control, p = 0.001). The bcl-2 expression was higher in both gosereline and raloxifene groups compared to control group (173.7 for gosereline versus 94.7 for control, 179.7 for raloxifene versus 94.7 for control, p = 0.001). The p53 expression was only lower with gosereline than the control group (169.4 versus 205.6, p = 0.001), whereas there was no significant change between the raloxifene group and the control group (201.9 versus 205.6) (p>0.05). CONCLUSION: Raloxifene was as effective as gosereline in reducing leiomyoma volumes. Decreased PR expression may be a mechanism for tumor growth reduction in raloxifene treatment. In both treatment modalities, the mechanism of shrinkage of leiomyomas could not be increased apoptosis mediated by bcl-2 and p53 expression and should be investigated by further studies.     

Fertility and uterine size among Asian women undergoing hysterectomy for leiomyomas

OBJECTIVE: To ascertain whether an epidemiological relationship exists between fertility and uterine leiomyomas, and whether uterine size is associated with fertility among Asian women undergoing hysterectomy for leiomyomas. METHODS: The study was conducted in Sapporo, Japan. 91 women undergoing hysterectomy for myomas were compared with age-matched controls with respect to reproductive factors. Further comparisons were made of these factors in women with large myomas and those with small ones. RESULTS: Women with leiomyomas were more likely to be nulliparous than controls (P < .01), and the risk of leiomyoma increased as the number of births decreased (P < .01). Time since last birth was associated with increased risk in women with large myomas (P < .05). Women with fewer births undergoing hysterectomy for leiomyomas tended to have greater uterine weight. CONCLUSION: Fewer births may be a cause of larger leiomyomas.     

Differential diagnosis of smooth muscle tumors utilizing p53, pTEN and Ki-67 expression with estrogen and progesterone receptors

BACKGROUND/AIM: To investigate the expression and value for diagnosis of the genes, p53 and pTEN, the protein, Ki-67, and the receptors, estrogen and progesterone, in differentiating smooth muscle tumors of the uterus. MATERIAL AND METHOD: Seventeen samples of leiomyosarcoma, 2 smooth muscle tumors with uncertain malignant potential (STUMP), 9 atypical myomas and 15 leiomyomas were stained immunohistochemically. The chi(2) test was used for the statistical analysis of the data. RESULTS: The malignant side of the spectrum was strongly stained for Ki-67 and p53 while uniformly decreasing toward the benign tumors. The results were found to be statistically significant (p < 0.0001). The staining for progesterone receptor was also statistically significant, but the tumors that were considered benign, such as leiomyoma and atypical myoma, were the ones strongly stained (p = 0.005). The expression of estrogen receptor was significant in these tumors, but the p value was very close to the cut-off value (p = 0.07). As the degree of differentiation of the tumor increased, the trend showed stronger staining for estrogen receptor. However, no difference was detected in the staining properties of the tumors for pTEN (p = 0.2457). CONCLUSION: The expression of Ki-67, p53 and progesterone receptors is promising in immunodifferentiation of smooth muscle tumors of the uterus with malignant potential.     

Ki-67 and vascular endothelial growth factor expression in uterine leiomyosarcoma

OBJECTIVE: Uterine leiomyosarcomas (LMS) are rare female neoplasms of high malignant potential. The importance of different prognostic parameters in these malignancies remains controversial. The aim of the present study was to evaluate the prognostic value of Ki-67 and vascular endothelial growth factor (VEGF) in uterine LMS. METHODS: Ki-67 and VEGF expression was assessed using immunohistochemistry from paraffin-embedded tissue in 20 patients with uterine LMS. RESULTS: Ki-67 was expressed in 10 of 20 cases (50%) of uterine LMS. A statistically significant positive correlation was observed between vascular space involvement and Ki-67 expression (P = 0.05). There was no statistically significant relationship between Ki-67 expression and clinical stage (P = 0.38), recurrent disease (P = 0.86), and age (P = 1.0). An expression of VEGF could be observed in 1 of 20 (5%) cases. The median disease-free survival was 13 months (range: 3-23 months). Eleven (55%) patients died of the disease with a median overall survival of 47.4 months (range: 1-227 months), resulting in a 5-year-overall survival rate of 45%. In a univariate analysis a statistically significant shortened disease-free survival in patients with Ki-67 positive tumors could be observed (P = 0.01). CONCLUSIONS: Our results suggest that the significant expression of Ki-67 in uterine LMS, correlating with vascular space involvement and being associated with a shortened disease-free survival, may be an indicator of the biological aggressiveness of these rare tumors.     

Positron emission tomography and leiomyomas: clinicopathologic analysis of 3 cases of PET scan-positive leiomyomas and literature review

INTRODUCTION: Studies have suggested that PET scans can differentiate between leiomyomas and leiomyosarcomas. Our experience, however, shows that PET scan-positive smooth muscle tumors are not necessarily malignant. CASE REPORTS: Three patients with cancer underwent PET imaging. In all three, the most worrisome finding was a PET scan-positive uterine tumor. After surgical extirpation, all three uterine tumors were found to be benign smooth muscle neoplasms. DISCUSSION: To explore the potential reason these tumors were positive on PET imaging, we performed a detailed histopathologic and immunohistochemical study of all specimens. Pathologic evaluation revealed a leiomyoma, a cellular leiomyoma, and a stromomyoma. There was no association between an increased Ki67 (proliferative) index and positivity on PET imaging. Increased vascularity, however, appeared to be a feature common to the leiomyomas that were PET-positive.