Vega Gabriel G, Avilés-Salas Alejandro, Chalapud J Ramón, Martinez-Paniagua Melisa, Pelayo Rosana, Mayani Héctor, Hernandez-Pando Rogelio, Martinez-Maza Otoniel, Huerta-Yepez Sara, Bonavida Benjamin, Vega Mario I
Oncology Research Unit, Oncology Hospital, Siglo XXI National Medical Center, IMSS, Mexico City, Mexico.
Facultad de Medicina Programa de Posgrado, Doctorado en Ciencias Biomédicas UNAM, México City, DF, Mexico.
BMC Cancer. 2015 Oct 16;15:722. doi: 10.1186/s12885-015-1778-8.
The p38 MAPK is constitutively activated in B-NHL cell lines and regulates chemoresistance. Accordingly, we hypothesized that activated p38 MAPK may be associated with the in vivo unresponsiveness to chemotherapy in B-NHL patients.
Tissue microarrays generated from eighty untreated patients with Diffused Large B Cell Lymphoma (DLBCL) were examined by immunohistochemistry for the expression of p38 and phospho p38 (p-p38) MAPK. In addition, both Bcl-2 and NF-κB expressions were determined. Kaplan Meier analysis was assessed.
Tumor tissues expressed p38 MAPK (82 %) and p-p38 MAPK (30 %). Both p38 and p-p38 MAPK expressions correlated with the high score performance status. A significant correlation was found between the expression p-p38 and poor response to CHOP. The five year median follow-up FFS was 81 % for p38(-) and 34 % for p38(+) and for OS was 83 % for p38(-) and 47 % for p38(+). The p-p38(+) tissues expressed Bcl-2 and 90 % of p-p38(-) where Bcl-2(-). The coexpression of p-p38 and Bcl-2 correlated with pool EFS and OS. There was no correlation between the expression of p-p38 and the expression of NF-κB.
The findings revealed, for the first time, that a subset of patients with DLBCL and whose tumors expressed high p-p38 MAPK responded poorly to CHOP therapy and had poor EFS and OS. The expression of p38, p-p38, Bcl2 and the ABC subtype are significant risk factors both p38 and p-p38 expressions remain independent prognostic factors.
p38丝裂原活化蛋白激酶（p38 MAPK）在B细胞非霍奇金淋巴瘤（B-NHL）细胞系中持续激活并调节化疗耐药性。因此，我们推测激活的p38 MAPK可能与B-NHL患者体内化疗无反应有关。
通过免疫组织化学检测80例未经治疗的弥漫性大B细胞淋巴瘤（DLBCL）患者的组织芯片中p38和磷酸化p38（p-p38）MAPK的表达。此外，还测定了Bcl-2和核因子κB（NF-κB）的表达。进行了Kaplan-Meier分析。
肿瘤组织表达p38 MAPK（82%）和p-p38 MAPK（30%）。p38和p-p38 MAPK的表达均与高评分体能状态相关。发现p-p38的表达与对CHOP方案反应不佳之间存在显著相关性。p38（-）组五年中位随访无进展生存期（FFS）为81%，p38（+）组为34%；总生存期（OS）方面，p38（-）组为83%，p38（+）组为47%。p-p38（+）组织表达Bcl-2，90%的p-p38（-）组织Bcl-2（-）。p-p38和Bcl-2的共表达与不良的无进展生存期和总生存期相关。p-p38的表达与NF-κB的表达之间无相关性。
研究结果首次揭示，一部分DLBCL患者肿瘤表达高水平p-p38 MAPK对CHOP治疗反应不佳，无进展生存期和总生存期较差。p38、p-p38、Bcl2的表达以及ABC亚型都是显著的危险因素，p38和p-p38的表达均为独立的预后因素。
