Abstract
In the present study we evaluated the expression of E-Cadherin, beta-catenin and TOP IIa proteins in a series of 71 liposarcoma, 19 leiomyosarcoma and 6 rabdomyosarcoma cases and investigated potential associations of these molecules with clinical outcome Expression of E-cadherin, beta-catenin and topoisomerase II alpha was examined immunohistochemically on formalin-fixed paraffin-embedded tissue specimens from the patients. All of them were diagnosed with primary, non-metastatic disease who underwent surgical treatment in two major cancer reference centers between 1990 and 2000. No other treatment was given to the patients before surgery. Weak and moderate expression of b-catenin protein was detected in 15 cases (21.1%). Similarly weak expression of TOP2α was detected in 14 (19.7%) cases. However, two of them had TOP2a expression in more than 20% of tumor cells. E-cadherin was not detected in the studied cohort of liposarcomas. No correlation was found between expression of beta-caten ...
In the present study we evaluated the expression of E-Cadherin, beta-catenin and TOP IIa proteins in a series of 71 liposarcoma, 19 leiomyosarcoma and 6 rabdomyosarcoma cases and investigated potential associations of these molecules with clinical outcome Expression of E-cadherin, beta-catenin and topoisomerase II alpha was examined immunohistochemically on formalin-fixed paraffin-embedded tissue specimens from the patients. All of them were diagnosed with primary, non-metastatic disease who underwent surgical treatment in two major cancer reference centers between 1990 and 2000. No other treatment was given to the patients before surgery. Weak and moderate expression of b-catenin protein was detected in 15 cases (21.1%). Similarly weak expression of TOP2α was detected in 14 (19.7%) cases. However, two of them had TOP2a expression in more than 20% of tumor cells. E-cadherin was not detected in the studied cohort of liposarcomas. No correlation was found between expression of beta-catenin or TOP2α and pathological parameters, such as tumor grade and histological subtype. Beta-catenin (either membranous or nuclear expression) was not associated with local recurrences (p=0.67), metastases (p=0.47) or death (p=0.47). Similarly, TOP2α was not associated with clinical outcome (p values of 0.52, 0.57 and 0.78 for local recurrences, metastases and death, respectively). None of the examined LMSs exhibited E-cadherin expression. Similarly, none of the LMSs showed positive nuclear b-catenin expression. Cytoplasmic b-catenin expression was seen in 11cases (57.9%). Ten patients had positive cytoplasmic b-catenin expression ranging from 80% to100% of tumor cells. Topoisomerase IIa was expressed in all but 2 LMS. In seven cases this expression was slight (ranging from 1% to 20%), while in 10 patients there was moderate to strong expression ranging from 30% to 100%. Among the examined clinical parameters only tumor size was a statistically significant factor associated with recurrence free survival. The hazard ratio was 1.15 [95% Confidence intervals: 1.03-1.28] (p =0.01). None of the examined RMSs showed E-cadherin expression. Similarly, none of them had positive nuclear b-catenin expression. Cytoplasmic b-catenin expression was seen in 2 patients. Both of them had strong expression of cytoplamsic b-catenin of 40% and 100%, respectively. Topoisomerase IIa was expressed in all but one RMS. All but one patient had strong expression (ranging from 50% to 90%). The two patients that had positive b-catenin staining had also high topoisomerase II expression. To our knowledge, this is the largest study that investigated E-cadherin, beta-catenin and topoisomerase II alpha expression in liposarcomas. Liposarcomas do not express E-cadherin, which reflects the absence of epithelioid differentiation in this sarcoma subtype. Low TOP2α expression, justifies in some extend their resistance to anthracycline-based chemotherapy. A major finding in our study was the predominately membranous localization of beta-catenin Given that degradation of membranous beta-catenin is linked to the invasiveness of several cancers, it can be inferred that to some extent membranous expression of beta-catenin in liposarcomas may associate with low metastatic potential of the majority of these tumors. As far as LMS were concerned the absence of E-cadherin expression in all our cases suggests that E-cadherin protein may not be correlated with the establishment and maintenance of cellular architecture in LMS. Also,given that the vast majority of LMSs expressed Topoisomerase IIa, probably implying the aggressive behavior of this type of tumors. Decreased E-cadherin expression can indicate either no involvement of this molecule in the constitution of RMS architecture, or reflect the aggressive behaviour of these neoplasms. On the other hand, the positive expression of b-catenin might be related to tumour proliferation and therefore poor prognosis. This could not be confirmed from our results (where only 2 out of 6 RMS had strong b-catenin expression), maybe due to the extremely limited sample size. Our literature search did not recognise any published data reporting on b-catenin expression in RMS. In our study five out of six samples showed high levels of positive topoisomerase IIa expression, although no definite associations with prognosis could be made. Further, larger studies are needed in order to confirm our results and to provide additional information about the possible role of these molucular markers expression in the treatment and disease progression of patients with SSTs.
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