RESUMO
BACKGROUND: The Wnt/ß-catenin signaling pathway is a major target of p53. ß-Catenin/p53 coexpression predicts poorer survival in carcinoma patients. Conversely, CD99 inhibits tumor metastasis through the Wnt/ß-catenin pathway. We therefore assessed p53, ß-catenin, and CD99 by immunohistochemistry. PATIENTS AND METHODS: We studied 45 patients with systemic anaplastic large-cell lymphoma (ALCL), including 20 anaplastic lymphoma kinase (ALK)-positive and 25 ALK-negative ALCL. ß-Catenin expression was analyzed using phospho-ß-catenin-S552 antibody because its nuclear localization indicates Wnt signaling. RESULTS: In this cohort, p53 expression was associated with ALK-negative ALCL. Furthermore, p53 or ß-catenin expression alone or ß-catenin/p53 double expression showed poorer overall survival and disease-free survival in patients with ALCL overall and in patients with ALK-negative ALCL. CD99 expression was more frequent in ALK-positive ALCL but had no prognostic significance. CONCLUSION: This is the first study to evaluate phospho-ß-catenin-S552 expression in ALCL. The results of this study, although limited by small patient size, suggest that ß-catenin and p53 may play a role in pathogenesis and may be helpful in risk stratification of ALCL patients.
Assuntos
Expressão Gênica , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/mortalidade , Proteína Supressora de Tumor p53/genética , beta Catenina/genética , Adolescente , Adulto , Idoso , Quinase do Linfoma Anaplásico/genética , Quinase do Linfoma Anaplásico/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Linfoma Anaplásico de Células Grandes/metabolismo , Linfoma Anaplásico de Células Grandes/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Adulto JovemRESUMO
p53 expression and MYC extra copies (MYC-EC) have been reported to serve as independent adverse prognostic markers in patients with diffuse large B-cell lymphoma (DLBCL). However, the impact of p53 expression in MYC-EC lymphomas has not been delineated. Conversely, CD99 expression has been shown to have a positive impact on survival in patients with germinal center-type DLBCL, yet nothing is reported about the impact of CD99 expression and MYC status. This is the first study to evaluate p53 expression in MYC-EC lymphomas and CD99 expression in relation to MYC status. We identified 122 patients diagnosed as having large B-cell lymphoma (44, MYC-negative; 29, MYC-EC; 23, MYC rearrangement; 22, MYC and BCL2 rearrangements; 4, MYC, BCL2, and BCL6 rearrangements). p53 expression significantly correlated with DLBCL with abnormal MYC status (MYC-EC, MYC rearrangement, and MYC overexpression), but adverse p53 prognostic effect was only seen with MYC-rearranged lymphoma. CD99 expression was significantly associated with MYC-negative DLBCL and had better prognostic impact on lymphoma-specific survival (LSS), but not on relapse-free survival and overall survival. Overall, patients with MYC-EC lymphoma had significantly worse relapse-free survival and LSS than did patients with MYC-negative lymphoma, yet better overall survival and LSS than did the patients with MYC-rearranged lymphoma. Thus, patients with MYC-EC lymphomas had prognostic features that were intermediate between MYC-negative and MYC-rearranged lymphomas. Lastly, high-intensity chemotherapy (either dose-adjusted rituximab and etoposide-prednisone-vincristine-cyclophosphamide-doxorubicin or rituximab and hyperfractionated cyclophosphamide-vincristine-doxorubicin-dexamethasone treatment) did not improve survival in patients with MYC-EC and MYC-rearranged lymphoma when compared with rituximab-cyclophosphamide-hydroxydaunomycin-vincristine-prednisone therapy.
