Alveolar soft part sarcoma: a bimarker diagnostic strategy using TFE3 immunoassay and ASPL-TFE3 fusion transcripts in paraffin-embedded tumor tissues.

Alveolar soft part sarcoma (ASPS) is a malignancy with low incidence, but with poor prognosis if misdiagnosed. Immunohistochemical assay using TFE3 antibody has been shown to be a sensitive technique for ASPS diagnosis. A specific chromosomal translocation, t(X;17)(p11.2;q25), results in the ASPL-TFE3 fusion gene: it is detectable using reverse-transcription polymerase chain reaction (RT-PCR) in frozen tumor tissues of ASPS. However, the diagnostic usefulness of these markers has not been investigated in Chinese ASPS patients. Here, we report the first systematic study applying TFE3 immunoassay and ASPL-TFE3 fusion transcript detection to archival paraffin-embedded tissues in a large Chinese ASPS patient population. Sixteen patients had been diagnosed with ASPS (age, 3 to 58 y; 3 male patients and 13 female patients). Their tumors presented predominantly in the extremities (8/16), and were often located in the region of the orbit when affecting infants and children (3/16). Others had tumors in the chest wall, breast, and right pubis, respectively. One patient exhibited a tumor in the renal hilum, a location that had not been previously reported. Two patients had tumor metastases in the lung and the brain. ASPS tumors showed the best immunoreactivity to the TFE3 antibody (16/16). However, their immunoreactivity to other antibodies, including myoglobin (13/16), actin (10/16), desmin (2/16), and vimentin (2/16), was of various degrees. Positive staining was observed for the neural markers, NSE (9/16) and CgA (7/16), respectively. Using a strategy of RT-PCR, followed by a nested PCR with a different primer set, we were able to detect the expression of the chimeric ASPL-TFE3 mRNA in 11 of the 16 ASPS tumors. Of these 11, 7 were type 1 ASPL-TFE3 and 4 were type 2 ASPL-TFE3, including the tumor located in the renal hilum. No expression of ASPL-TFE3 fusion transcripts was detectable in all 38 control tumors. Our results demonstrate that the "bimarker strategy," a combination of TFE3 immunostaining and ASPL-TFE3 chimeric transcript detection, might have sufficient sensitivity and specificity in diagnosing most of the ASPSs. As both diagnostic techniques can be applied to widely available archival paraffin-embedded tissues, the usefulness of the strategy is largely implicated in routine pathology laboratories.