Potential Value of YAP Staining in Rhabdomyosarcoma

Abstract

Rhabdomyosarcoma (RMS) is a common malignancy of soft tissue, subclassified as alveolar (ARMS), pleomorphic (PRMS), spindle cell/sclerosing (SRMS), and embryonal (ERMS) types. The Yes-associated protein (YAP) is a member of the Hippo pathway and a transcriptional regulator that controls cell proliferation. We have studied the immunohistochemical expression of YAP in different RMSs, arranged in tissue microarray (TMA) and whole slide formats. Pertinent clinical data including patient age, gender, tumor location, and clinical stage were collected. Out of 96 TMA cases, 30 cases (31%) were pleomorphic, 27 (28%) were embryonal, 24 (25%) alveolar, and 15 (16%) spindle cell. Positive nuclear YAP staining was seen in the PRMS (17/30, 56.7%), SRMS (7/15, 46.7%), ERMS (19/27 or 70%), and less in ARMS (37.5%). YAP nuclear staining was significantly more prevalent in ERMS than ARMS ( p=0.02). Of the 41 whole slide cases, nuclear staining was detected in all ARMS but was restricted in distribution to <30% of the cells, in contrast to ERMS and SRMS, which had diffuse or >30% staining. These results highlight the role of YAP in RMS tumorigenesis, a fact that can be useful in engineering targeted therapy. Restricted nuclear YAP staining (<30% of cells) may be of value in the diagnosis of ARMS.

Establishment and Characterization of a Cell Line (S-RMS1) Derived from an Infantile Spindle Cell Rhabdomyosarcoma with SRF-NCOA2 Fusion Transcript

“…An increased expression of YAP has been described in many human adult and pediatric cancers, and its expression is associated with an advanced clinical stage and short overall survival in different tumors [ 28 ]. Several studies have revealed that nuclear YAP is more prevalent in ERMS and SRMS than in ARMS, even if its role in RMS has not been clarified yet [ 29 , 30 ]. Furthermore, at a transcriptional level, S-RMS1 showed a higher level of the neovascularization markers endoglin [ 22 ] and GATA-6 [ 31 ] while TGFβ1R was downregulated.…”

A rare case in an 11-year old child with bilateral primary orbital rhabdomyosarcoma with rapid onset of bilateral proptosis and temporal lobe abscess secondary to chronic suppurative otitis media

“…3 Yes-associated protein (YAP) is associated with sarcoma genesis in RMS patients and is more prevalent in ERMS than ARMS, thus differentiating the two. 13 The differential diagnosis of orbital RMS includes proptosis secondary to inflammatory, infectious, vascular, and neoplastic conditions, and thus careful histological examination is required to differentiate such lesions. 14 In our case, the marked pleomorphism noted was critical for differentiating RMS from Ewing's sarcoma.…”