(P 379) IMPACT OF EWSR1 GENE REARRANGEMENT TESTING ON DIAGNOSIS OF A WIDE RANGE OF SOLID TUMOURS

Objective: EWSR1 gene rearrangement is seen in a wide variety of tumours, Ewing sarcoma (ES) being the commonest of all. It serves as a diagnostic tool in conjunction with clinical presentation, tumour morphology and immunohistochemistry (IHC). We present our data of 143 patients who have undergone testing for EWSR1 gene rearrangement with a focus on real impact of this molecular test on diagnostic process.

Methods: This is a retrospective observational study wherein we reviewed clinical features, tumour morphology and IHC along with results of EWSR1 gene rearrangement performed by fluorescent in-situ hybridization (FISH) technique of tumours from 143 patients. Clinical and demographic data was obtained from electronic medical records.

Results: 49% of all patients were diagnosed with ES based on tumour morphology and IHC. NKX2.2 was uniformly expressed in all ES on IHC. 92% of ES had EWSR1 gene rearrangement. 27% of tumours diagnosed histologically as undifferentiated round cell tumours (RCTs) and 25% of other high grade sarcomas, not otherwise specified (NOS) demonstrated EWSR1 gene rearrangement, hence were considered as ES after molecular testing. All 4 tumours with strong and diffuse positivity for BCOR IHC were negative for EWSR1 rearrangement. All 7 patients diagnosed with hylanising clear cell carcinoma of salivary gland showed EWSR1 gene rearrangement. 6 of 10 patients with EWSR1 gene rearrangement helped distinguish clear cell sarcoma from malignant melanoma. We also found EWSR1 rearrangement in one case each of sclerosing epithelioid fibrosarcoma (SEF) and angiomatoid fibrous histiocytoma (AFH) respectively.

Conclusion: ES is characterized by EWSR1 gene rearrangement. IHC for NKX2.2 is a robust tool for definitive diagnosis of ES as seen in our results. Similarly, tumours with strong BCOR positivity on IHC lacked EWSR1 gene rearrangement. Thus it may be concluded IHC is a strong surrogate for molecular testing in these cases. However, EWSR1 gene rearrangement seen in 25% of undifferentiated round cell sarcomas highlighting its significance and also limitations of IHC. EWSR1 testing had significant impact on distinction between malignant melanoma and clear cell sarcoma and diagnosis of rare tumours such as hylanising clear cell carcinoma of salivary glands, SEF and AFH. While distinction between ES and DSRCT was not possible based on EWSR1 status, it was helpful to differentiate ES from rhabdomyosarcoma.