[1955] DAX-1 and ap2 beta Are Liable Markers of Translocation Positive Alveolar Rhabdomyosarcoma (ARMS)

Benedetta Di Venosa, Angelo Rosolen, Angelica Zin, Enzo Lalli, Vincenza Guzzardo, Rita Alaggio. Padua University, Padua, Italy; CNRS UMR, Valbonne, France

Background: ARMS are characterized by fusions of FOXO1 gene on chromosome 13 with PAX3 gene on chromosome 2 or PAX7 gene on chromosome 1 in 80% of case. Translocation positive ARMS have a distinctive biological signature on expression array. Among other genes ap2 beta and DAX-1 have been found to be over-expressed in translocation positive ARMS and a strong and diffuse nuclear immunostaining for ap2 beta appears to be predictive of presence of translocation.
Design: We studied a series of 45 ARMS (37 classic and 8 with areas of embryonal rhabdomyosarcoma-ERMS) and 25 ERMS to test the role of ap2 beta and DAX- 1 expression in predicting molecular status of ARMS.Immunostains for desmin, myogenin, ap2 beta and DAX-1 were performed. Ap2 beta and DAX-1 were considered positive when a strong and diffuse nuclear staining was found in the majority of cells.
Results: All tumors were desmin and myogenin positive, with staining for myogenin in more than 50% of cells in 78% of ARMS and 20% of ERMS respectively. Ap2 beta and DAX-1 pattern of expression are summarized in Table 1.

Ap2 beta and DAX-1 pattern
Diagnosis (70 cases)Ap2beta+/DAX1+Ap2beta+/DAX-1-Ap2beta-/DAX-1+Ap2beta-/DAX-1-
ARMS t+ (32)25232
Arms t- (5)0131
ERMS (25)10519
MIXED (ARMS+ERMS, t-) (8)2042
Legend: t+: translocation positive, t-: translocation negative.

Translocation positive ARMS show a characteristic ap2beta+ and DAX-1 + staining in 78% of cases, while 76% of classic ERMS are negative for both. Ap2 beta alone was positive in 2.6% of rhabdomyosarcomas lacking translocation whereas DAX-1 alone was positive in 31.5%, by contrary 9% and 6% of translocation positive ARMS were positive only for DAX-1 or Ap2beta respectively.Mixed ARMS and ARMS t- share the same phenotype as ERMS but have a higher frequency of DAX-1 expression (20% vs 53%).
Conclusions: Compared to Ap2 beta, DAX-1 is less specific but highly sensitive. Our results suggest that the combined use of ap2 beta and DAX-1 might be helpful in identifying classic ARMS with translocation.
Category: Pediatrics

Monday, March 19, 2012 1:00 PM

Poster Session II # 236, Monday Afternoon


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