Immunohistochemical study and fluorescent in situ hybridization analysis of JAZF1 in 67 cases of endometrial stromal tumors collected in a tissue microarray.

Abstract

10069 Background: Endometrial stromal tumours are rare uterine lesions comprising undifferentiated endometrial sarcoma (UES), endometrial stromal sarcoma low grade (ESS) and stromal nodule (SN). Complex caryotypes and frequent 7p deletion are found in the malignant types, and a translocation t(7;17) involving two finger zinc gene JAZF1 and JJAZ1/SUZ12 has also been recently described. Methods: We performed an immunohistochemical study to evaluate the expression of oestrogen and progesterone receptors, Ki67, P16 and P53 and a in situ fluorescent hybridization (FISH) studying JAZF1(7p15) locus using formalin fixed paraffin embedded tissues of 12 SN, 41 ESS and 14 UES collected in a tissue microarray. Results: Immunohistochemical analysis of SN and ESS showed a high nuclear expression of both oestrogen receptor (OR) and progesterone receptor (PR), associated with a low nuclear expression of Ki67, P16 and P53. In opposite, UES exhibit a low expression of OR and PR and a high nuclear expression of Ki67, P16 and P53. The difference for each of the immunostainings was highly statistically significant between ESS and UES (p<0,0005), but not between SN and ESS. Among the 44 cases with available FISH status, the dissociation of JAZF1 (7p15) meaning the specific translocation was found in 25% of SN (n=2/8), 35% of ESS (n=8/23), and was absent in UES (n=0/13). Interestingly, we observed also a deletion of the second allele of the JAZF1 gene in 80% of the 10 cases with dissociation of JAZF1. Conclusions: Immunohistochemical analysis of OR, PR, P16, P53 and Ki67 could be very useful for the differential diagnosis of endometrial stromal tumours especially between ESS and UES. The absence of JAFZ1 dissociation in UES suggest different oncogenic pathways between UES and NS/ESS, that support the current World Health Organization classification of tumours. Moreover, the translocation was associated in 80% with deletion of second JAZF1 allele suggesting a loss of function of the gene. However, further study are necessary to find out the regulatory consequences of JAZF1 function's loss and translocation. No significant financial relationships to disclose.