Differentiation between endometrial stromal sarcomas (ESSs) and clean muscle tumors of

Differentiation between endometrial stromal sarcomas (ESSs) and clean muscle tumors of the uterus can be challenging. CD10 was positive in most ESSs. Transgelin appears to be a specific marker of easy muscle differentiation in the uterus with 100% sensitivity and specificity and may be useful for distinguishing LMS from ESS. It could be used as ATP2A2 an additional marker useful for decision making especially in those tumors with questionable histology. Keywords: Transgelin endometrial stromal sarcoma leiomyosarcoma I. Introduction Uterine sarcomas are rare mesenchymal neoplasms that comprise about 7% of all soft tissue tumors Miglustat HCl Miglustat HCl and up to 3% of uterine malignancies.1 2 Excluding carcinosarcomas (Malignant Mixed Müllerian Tumors) endometrial stromal sarcoma (ESS) and leiomyosarcoma (LMS) represent the majority of this group of tumors.2 3 Traditionally ESS has been categorized into low and high grade tumors based on mitotic activity and the morphologic resemblance of the tumor to endometrial stroma.3-5 Currently the World Health Organization (WHO) classifies these tumors into low grade and undifferentiated sarcomas.3 Low grade ESSs are composed of neoplastic cells that still resemble the normal benign proliferative endometrium but with definite evidence of myometrial invasion in the characteristic “finger-like” infiltrative pattern.6 7 They are also known to frequently have lympho-vascular invasion.6 7 In contrast undifferentiated ESSs lack evidence of endometrial stromal differentiation and are clinically more aggressive.3 Recent studies have shown that some of the undifferentiated ESSs have an immunohistochemical and molecular profile that overlaps with that of low grade ESS.8-10 The authors of these studies argue the need for the reclassification of ESS into the current low grade ESS and the splitting of undifferentiated ESS into high grade ESS because of evidence of lower grade component in the tumor and the truly undifferentiated ESS. The morphologic distinction between ESS and LMS is not straightforward and at times has been shown to be challenging with poor reproducibility. The use of immunohistochemistry with a battery of markers including easy muscle actin (SMA) desmin actin h-caldesmon and CD10 have been proposed to be of value.10-15 However the current immunohistochemical (IHC) panel has been shown to be not entirely specific and less helpful in this regard.12-14 16 17 Transgelin a 22 kDa actin-binding protein of the calponin family is a novel marker that recently has been shown to correlate with clean muscle differentiation.18-21 The promoter of the gene is the target of the transcriptional activator serum response factor of which myocardin acts as a cofactor.21 By using gene expression profiling studies have shown that transgelin was one of the most promising markers for the leiomyosarcomatous differentiation. A Miglustat HCl recent gene expression signature study exhibited an overexpression of several genes including transgelin in LMS as compared to ESS confirming molecular differences between uterine ESS and LMS.22 The goal of this study was to determine if transgelin a easy muscle-specific marker could accurately distinguish ESS from uterine easy muscle tumors and LMS from other body sites. II. Methods This retrospective study was approved by the institutional review committee at the University of Kansas Medical Center. A total of 37 patients diagnosed between 2002 and 2012 were Miglustat HCl studied. These are composed of 13 ESSs 1 uterine leiomyoma 8 uterine LMSs and 15 extra uterine soft tissue LMSs. All tumors were graded using the WHO grading system. At diagnosis tissue blocks containing the most representative and well-preserved tumor areas were selected for IHC analysis. Immunohistochemistry was performed on tissue fixed with 10% neutral buffered formalin. IHC analyses for transgelin (Anti-SM22 alpha antibody (ab14106); pre-treatment: citrate antigen retrieval in the Biocare pressure cooker; dilution: 1:3000; source: abcam Cambridge Massachusetts) CD10 (clone 56C6; pre-treatment: CC1 prediluted; source: Cell Marque Rocklin California) and SMA (clone: 1A4; pre-treatment: CC1; prediluted; source: Cell Marque Rocklin California) were performed. Positive IHC reactions were defined as dark brown reaction.