title: Relationship of endothelial area with VEGF-A, COX-2, maspin, c-KIT, and DOG-1 immunoreactivity in liposarcomas versus non-lipomatous soft tissue tumors.
abstract: Soft tissue tumors are rare tumors that show a heterogeneous structure; thus far, their molecular behavior has not been elucidated. The aim of our study was to define the relationship between microvessel density (MVD), evaluated with CD31, and other immunohistochemical markers, such as vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), CD34, maspin, DOG-1, and c-KIT. Immunostains were done in 55 cases consisting of benign and malignant tumors, such as liposarcomas, dermatofibrosarcomas, and tumors with histiocytic differentiation. Renal tubes were used as external control for VEGF, maspin, and DOG-1. Although DOG-1 is considered a specific marker for gastrointestinal tumors (GISTs), its positivity, correlated with c-KIT and VEGF immunoexpression, was also shown by dermatofibrosarcomas and tumors with histiocytic and lipomatous differentiation, suggesting its possible pro-angiogenic role. Maspin expression was observed in adipose tissue tumors only. Regarding angiogenesis, 31 of the 55 cases were VEGF-positive, such positivity being directly correlated with COX-2 and CD34 positivity as evaluated in the tumor cells and also with MVD. Although no significant differences in angiogenic activity were found between benign and malignant non-lipomatous tumors, the MVD was directly correlated with the histological type/grade of liposarcomas. Based on these aspects, we conclude that VEGF/COX-2-induced angiogenesis is specific for non-lipomatous tumors, whereas liposarcomas are dependent on the VEGF/maspin angiogenic pathway. The DOG-1/c-KIT/VEGF target may be used for further personalized therapy of soft tissue sarcomas. No data about DOG-1 and maspin positivity in liposarcomas have been published to date.
authors.affiliation: Department of Pathology, University of Medicine and Pharmacy Tirgu-Mures, Romania.
authors.forename: Ioan
authors.initials: I
authors.lastname: Jung
authors.affiliation: Department of Pathology, University of Medicine and Pharmacy Tirgu-Mures, Romania.
authors.forename: Simona
authors.initials: S
authors.lastname: Gurzu
authors.affiliation: Department of Pathology, University of Medicine and Pharmacy Tirgu-Mures, Romania.
authors.forename: Sabin
authors.initials: S
authors.lastname: Turdean
authors.affiliation: Department of Pathology, University of Medicine and Pharmacy Tirgu-Mures, Romania.
authors.forename: Diana
authors.initials: D
authors.lastname: Ciortea
authors.affiliation: Department of Pathology, University of Medicine and Pharmacy Tirgu-Mures, Romania.
authors.forename: Danut Ioan
authors.initials: DI
authors.lastname: Sahlean
authors.affiliation: Department of Pathology, University of Medicine and Pharmacy Tirgu-Mures, Romania.
authors.forename: Mircea
authors.initials: M
authors.lastname: Golea
authors.affiliation: Department of Surgery, University of Medicine and Pharmacy Tirgu-Mures, Romania.
authors.forename: Tivadar
authors.initials: T
authors.lastname: Bara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000075369:Anoctamin-1; D018118:Chloride Channels / Q000032:analysis*; D051546:Cyclooxygenase 2 / Q000032:analysis*; D042783:Endothelial Cells / Q000737:chemistry* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008080:Liposarcoma / Q000098:blood supply / Q000737:chemistry* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009389:Neovascularization, Pathologic; D011237:Predictive Value of Tests; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis*; D015843:Serpins / Q000032:analysis*; D012983:Soft Tissue Neoplasms / Q000098:blood supply / Q000737:chemistry* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*
chemical_list: C476213:ANO1 protein, human; D000075369:Anoctamin-1; D018118:Chloride Channels; D009363:Neoplasm Proteins; C085344:SERPIN-B5; D015843:Serpins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019009:Proto-Oncogene Proteins c-kit
keywords: COX-2; DOG-1; Soft tissue; angiogenesis; c-KIT; maspin