RESUMO
Recent studies show that AC133-a hematopoietic stem cell antigen, when coex-pressed with endothelial markers, identifies a population of endothelial precursor cells (EPCs) in peripheral blood that function in tumor vasculogenesis in animals. Little is known about whether EPCs contribute to human tumor vasculogenesis. We attempted to determine if, through increased peripheral expression of AC133 or endothelial markers previously associated with EPCs,VEGFR-2 and Tie-2, we could detect an EPC response in the blood of patients with breast carcinoma. Thirty patients were segregated based on their breast biopsy histology into infiltrating carcinoma, DCIS and control groups. Using Real Time PCR, we measured the expression of the aforementioned markers in reverse transcribed RNA extracts from preoperative peripheral blood specimens. The cancer patients had significantly elevated Tie-2 expression with the highest levels associated with infiltrating carcinoma. Our data suggest increased circulating EPC markers in tumor patients, but further study of this cell population is needed to better define its role in tumor vasculogenesis.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/irrigação sanguínea , Endotélio Vascular/metabolismo , Proteínas de Neoplasias/genética , Neovascularização Patológica/sangue , Antígeno AC133 , Antígenos CD , Carcinoma Ductal de Mama/irrigação sanguínea , Carcinoma Intraductal não Infiltrante/irrigação sanguínea , Primers do DNA/química , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Glicoproteínas/genética , Humanos , Peptídeos/genética , RNA Mensageiro/metabolismo , Receptor TIE-2/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genéticaRESUMO
Classic Hodgkin lymphoma (cHL) is characterized by numerical gains of the short arm of chromosome 2. The high frequency of 2p overrepresentation including REL, particularly in the nodular sclerosis subtype suggests that constitutive activation of nuclear factor kappaB/REL is a hallmark of Reed-Sternberg (RS) cells. The aim of this study was to investigate c-Rel protein expression patterns in cHL and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) cases by immunohistochemical analysis. A total of 79 cases of HL were analyzed, which included 59 cases of cHL (49 nodular sclerosis; 8 mixed cellularity; 2 lymphocyte-rich) and 20 cases of NLPHL. Positive staining was defined in this study as a reaction seen in the nuclei or nuclei and cytoplasm of RS or lymphocytic and histiocytic (L&H) cells in cHL and NLPHL cases, respectively. The percent positivity of c-REL staining of RS cells in cHL was seen in 51 of 59 cases (86.4%). No significant difference in c-REL expression was seen between nodular sclerosis (42 of 49, 85.7%) and mixed cellularity subtypes (7 of 8 cases, 87.5%; P = 1). In comparison, positive c-REL protein expression in L&H cells was seen in 5 of 20 NLPHL cases (25.0%). Therefore, significantly higher positivity of RS cells in cHL was seen compared with positivity of L&H cells in NLPHL; 86.4% vs. 25.0%; P = 0). Expression of Epstein-Barr virus latent membrane protein was seen in 6 of 30 cases (19.0%; 25 cHL, 5 NLPHL) and EBER1 in 5 of 27 cases (18.5%; 24 cHL, 3 NLPHL). The presence of Epstein-Barr virus did not correlate with c-REL protein expression (P = 1). Our results demonstrate that there is differential c-REL protein expression in cHL in comparison with NLPHL and suggest that c-REL may play a role in the pathogenesis of classic Hodgkin lymphoma.