Title

Grb2-associated binding protein-1 as a biomarker in bone and soft tissue sarcomas.

Document Type

Article

Publication Date

10-2019

Identifier

DOI: 10.1016/j.pathol.2019.05.003

Abstract

The Grb2-associated binding proteins are a family of platform proteins involved in signalling transduction pathways. A major family member, Gab1, modulates the effect of growth factor receptors and intracellular signalling pathways, including the phosphatidylinositol 3-kinase and AKT/mTOR signalling pathways. We have studied the immunohistochemical staining of Gab1 in four separate tissue microarray slides containing Ewing sarcoma, rhabdomyosarcoma, osteosarcoma and synovial sarcoma. The expression of Gab1 was correlated with age, gender, tumour location and clinical stage. Positive staining was identified in 18/32 (56.25%) of Ewing sarcoma, 46/96 (48%) of rhabdomyosarcoma, 18/50 (36%) of synovial sarcoma, and 10/40 (25%) osteosarcoma. Of the 46 positive rhabdomyosarcoma cases, the staining was more prevalent in conventional embryonal (15/27 cases) and pleomorphic (21/30) subtypes than spindle cell (2/15) and alveolar types (8/24). For rhabdomyosarcoma and synovial sarcoma, positive Gab1 staining was significantly more prevalent in tumours of high clinical stage disease (stages III and IV) than low stages (I and II), (p=0.0042 and p=0.0024, respectively). Similarly, Gab1 staining in Ewing sarcoma revealed a significant association with advanced clinical stages (p=0.0189). In conclusion, Gab1 expression in Ewing sarcoma, rhabdomyosarcoma and synovial sarcoma may have prognostic significance and should be further exploited for potential benefit from targeted therapy. These findings are to be confirmed by larger studies with better represented patient populations.

Journal Title

Pathology

Volume

51

Issue

6

First Page

610

Last Page

614

MeSH Keywords

Adaptor Proteins, Signal Transducing; Adolescent; Adult; Age Factors; Biomarkers, Tumor; Bone Neoplasms; Child; Child, Preschool; Female; Humans; Immunohistochemistry; Infant; Male; Neoplasm Staging; Prognosis; Sarcoma; Sex Factors; Soft Tissue Neoplasms; Young Adult

Keywords

Ewing sarcoma; Gab1; biomarker; immunohistochemistry; rhabdomyosarcoma; synovial sarcoma; tissue microarray

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