title: Coordinate expression of colony-stimulating factor-1 and colony-stimulating factor-1-related proteins is associated with poor prognosis in gynecological and nongynecological leiomyosarcoma.
abstract: Previously, we showed that the presence of high numbers of macrophages correlates with poor prognosis in nongynecological leiomyosarcoma (LMS). In gynecological LMS, a similar trend was noted but did not reach statistical significance. Colony-stimulating factor-1 (CSF1) is a major chemoattractant for macrophages. Here we show that in a subset of LMS cases, CSF1 is expressed by the malignant cells. Previously, we found that CSF1 is translocated and highly expressed in tenosynovial giant cell tumors (TGCTs), and this observation allowed us to identify genes that showed a coordinate expression with CSF1. Here, we evaluated the expression of CSF1 and TGCT-associated proteins in 149 cases of LMS. The coordinate expression of CSF1 and three TGCT-associated proteins (CD163, FCGR3a, and CTSL1) identified cases with poor prognosis in both gynecological LMS (P = 0.00006) and nongynecological LMS (P = 0.03). In gynecological LMS, the coordinate expression of these four markers was the only independent prognosticator in multivariate analysis (hazard ratio, 4.2; 95% CI, 1.12 to 16; P = 0.03). Our findings indicate that CSF1 may play an important role in the clinical behavior of LMS that may open a window for new therapeutic reagents.
authors.affiliation: Dept. of Pathology, L-235, Stanford University Medical Center, 300 Pasteur Dr., Stanford, CA 94305, USA.
authors.forename: Inigo
authors.initials: I
authors.lastname: Espinosa
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Beck
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Lee
authors.forename: Shirley
authors.initials: S
authors.lastname: Zhu
authors.forename: Kelli D
authors.initials: KD
authors.lastname: Montgomery
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Marinelli
authors.forename: Kristen N
authors.initials: KN
authors.lastname: Ganjoo
authors.forename: Torsten O
authors.initials: TO
authors.lastname: Nielsen
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
authors.forename: Robert B
authors.initials: RB
authors.lastname: West
authors.forename: Matt
authors.initials: M
authors.lastname: van de Rijn
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis*; D056668:Cathepsin L; D002403:Cathepsins / Q000096:biosynthesis; D003546:Cysteine Endopeptidases / Q000096:biosynthesis; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D007890:Leiomyosarcoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D011379:Prognosis; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D017452:Receptors, IgG / Q000096:biosynthesis; D046888:Tissue Array Analysis; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D014408:Biomarkers, Tumor; D000098902:CD163 Antigen; C496124:FCGR3A protein, human; D011956:Receptors, Cell Surface; D017452:Receptors, IgG; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L