Expression and genomic status of EGFR and ErbB-2 in alveolar and embryonal rhabdomyosarcoma

Abstract

Both epidermal growth factor receptor (EGFR) and ErbB-2 play an important role in cancer biology and constitute promising molecular targets of therapy. EGFR and ErbB-2 expression has been observed in rhabdomyosarcoma cell lines but not analyzed systematically in rhabdomyosarcoma tumors. Tissue microarray sections representing 66 rhabdomyosarcoma tumors (34 embryonal rhabdomyosarcoma, 32 alveolar rhabdomyosarcoma) were surveyed by immunohistochemistry using antibodies specific for EGFR and ErbB-2. Immunostains were assessed for intensity (0: no immunostaining; 1: weak; 2: moderate; 3: strong) and percentage of at least 500 neoplastic cells exhibiting membranous or membranous and cytoplasmic immunostaining. EGFR and ErbB-2 expression was considered positive if the product of intensity and percentage was greater than 10. Patients had a median age of 5.7 years (range 8 months-19.1 years), and of 65/ 66 patients, 38 were males and 27 were females. Expression of ErbB-2 was identified in 22/66 (33%) cases and tended to be more frequent in the alveolar subtype (13/32, 41%, vs 9/34, 26%, P ¼ 0.30). Expression of EGFR was identified in 31/66 (47%) cases and correlated with the embryonal subtype (26/34, 76%, vs 5/32, 16%, Po0.0001) independent of stage, age, and gender. Coexpression of EGFR and ErbB-2 was identified in eight tumors, of which six were embryonal rhabdomyosarcoma. None of the cases exhibited EGFR or ErbB-2 gene amplification, as assessed using fluorescence in situ hybridization. Furthermore, analysis of 11 additional rhabdomyosarcoma tumors (six alveolar; five embryonal) revealed no evidence of mutations in EGFR exons 18, 19, 20, and 21. In summary, expression of EGFR and/or ErbB-2 is detected in a sizeable subset of rhabdomyosarcoma tumors without evidence of EGFR or ErbB-2 amplification or mutations in the EGFR tyrosine kinase domain. Notably, expression of EGFR correlates with the embryonal subtype, which is also more likely to coexpress EGFR and ErbB-2.

Prognostic significance of HER2 expression in neuroblastic tumors

“…29 In our survey of 79 tumors, we analyzed both membranous and cytoplasmic labeling, according to the phenomenon that in pediatric tumors, HER2 expression is frequently cytoplasmic. 13,16,26 Sixteen cases were HER2 immunonegative, 34 showed low and 29 high expression. Performed FISH analysis disclosed no evidence of HER2 amplification in the studied group.…”

EGFR and gastrointestinal stromal tumor: an immunohistochemical and FISH study of 82 cases

“…The role of EGFR has been studied in several types of human sarcomas, [22][23][24][25][26][27][28][29][30] mainly in synovial sarcomas. 14,23,29 On the other hand, very few reports about the relationship between GIST and EGFR have been published so far.…”

Recent advances in the molecular pathology of soft tissue sarcoma: Implications for diagnosis, patient prognosis, and molecular target therapy in the future

“…(26) This result indicates the benefits of treatment with biospecific inhibitors for EGFR in STS patients, as recently demonstrated in several kinds of carcinoma patients. Frequent immunohistochemical expression of EGFR without gene amplification has been reported in embryonal-type rhabdomyosarcoma (63) and SS18-SSX1-type synovial sarcoma, (64) compared with alveolar-type rhabdomyosarcoma and SS18-SSX2 synovial sarcoma, respectively. Moreover, the combination of EGFR blockage and conventional chemotherapy has been reported to inhibit the growth of STS cells in vitro and in vivo.…”