The molecular analysis of the t(11;22) rearrangement involving EWS/FLI-1 genes is likely to be of diagnostic value in Ewing sarcoma (ES) and primitive neuroectodermal tumors (PNET). The objective of the current study was to analyze the immunohistochemical expression of the EWS and FLI-1 proteins in a group of small round-cell tumors (SRCT) to determine their specificity and relevance in their differential diagnosis. Forty-eight cases-10 conventional ES, 4 large-cell ES, 5 PNET, 9 neuroblastomas (NB), 6 undifferentiated synovial sarcomas (SS), 5 rhabdomyosarcomas (RB), 5 non-Hodgkin lymphomas (NHL), 1 round-cell liposarcoma, and 3 mesenchymal chondrosarcomas-were analyzed. Immunocytochemistry was performed on paraffin sections after the LSAB method and antigen retrieval using ethylenediaminetetraacetic acid buffer (pH 6). Primary antibodies included FLI-1 (C-19), EWS (N-18), EWS (C-19), and CD99 (MIC-2). As expected, CD-99 expression was found in 100% of ES/PNET cases, in 2 cases of RB, 2 SS, and 1 NHL. FLI-1 protein was observed as nuclear staining in 16 cases of ES/PNET (84%) and in 4 cases of NHL, 2 NB, and 3 SS. Normal endothelial cells and lymphocytes also were positive. EWS expression (both proteins N-18 and C-19) was detected not only in 95% of ES/PNET cases but also in more than 50% of cases from the other tumoral types (4 of 9 and 7 of 9 NB, 5 of 6 and 6 of 6 SS, 3 of 5 and 5 of 5 RB, and 2 of 5 and 3 of 5 NHL, respectively). Whereas EWS expression does not appear specific for ES/PNET, analysis of FLI-1 expression together with CD-99 is a powerful marker for ES/PNET and important factors in the differential diagnosis of SRCT.

Background: Aromatase (CYP19A1) regulates estrogen biosynthesis. Polymorphisms inCYP19A1have been related to the pathogenesis of breast cancer (BC). Inhibition of aromatase with letrozole constitutes the best option for treating estrogen-dependent BC in postmenopausal women. We evaluate a series of polymorphisms ofCYP19A1and their effect on response to neoadjuvant letrozole in early BC.Methods: We analyzed 95 consecutive postmenopausal women with stage II-III ER/PgR [+] BC treated with neoadjuvant letrozole. Response to treatment was measured by radiology at 4^thmonth by World Health Organization (WHO) criteria. Three polymorphisms ofCYP19A1, one in exon 7 (rs700519) and two in the 3'-UTR region (rs10046 and rs4646) were evaluated on DNA obtained from peripheral blood.Results: Thirty-five women (36.8%) achieved a radiological response to letrozole. The histopathological and immunohistochemical parameters, including hormonal receptor status, were not associated with the response to letrozole. Only the genetic variants (AC/AA) of the rs4646 polymorphism were associated with poor response to letrozole (p = 0.03). Eighteen patients (18.9%) reported a progression of the disease. Those patients carrying the genetic variants (AC/AA) of rs4646 presented a lower progression-free survival than the patients homozygous for the reference variant (p = 0.0686). This effect was especially significant in the group of elderly patients not operated after letrozole induction (p = 0.009).Conclusions: Our study reveals that the rs4646 polymorphism identifies a subgroup of stage II-III ER/PgR [+] BC patients with poor response to neoadjuvant letrozole and poor prognosis. Testing for the rs4646 polymorphism could be a useful tool in order to orientate the treatment in elderly BC patients.