Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
Eur J Cancer. 2010 Sep;46(13):2506-12. doi: 10.1016/j.ejca.2010.06.014. Epub 2010 Jul 12.
Tumour-infiltrating mast cells (MCs) can remodel tumour microenvironment and growth by suppressing immune responses and potentiating angiogenesis. Furthermore, accumulation of MCs in follicular lymphoma (FL) correlates with unfavourable prognosis after immunochemotherapy. Here we investigated whether tumour vascularity is associated with MC content and outcome in FL patients treated with immunochemotherapy.
Microvessel density (MVD) and MC content were determined immunohistochemically from pretreatment samples of 95 FL patients using CD31, CD34 and mast cell tryptase antibodies. Gene expression data from a separate set of 24 FL patients were analysed for comparison. All patients were treated with the combination of rituximab (R) and cyclophoshamide-doxorubicin-vincristine-prednisone (CHOP) chemotherapy.
Increased CD31+ MVD correlated positively with the number of tumour infiltrating MCs and CD34+ vessels, and negatively with the outcome. Overall survival and progression-free survival were significantly better among patients with low CD31+ MVDs. In multivariate analyses, CD31+ MVD had prognostic value independently of Follicular Lymphoma Prognostic Index but not of MC content. Consistent with the immunohistochemical data, high CD31/PECAM1 mRNA levels were associated with adverse outcome. Conversely, a positive prognostic impact of VEGF mRNA expression on the outcome was found.
Vascularity is associated with MC content and outcome in R-CHOP-treated FL patients.
肿瘤浸润肥大细胞(MCs)可通过抑制免疫反应和促进血管生成来重塑肿瘤微环境和生长。此外,滤泡性淋巴瘤(FL)中 MC 的积累与免疫化疗后不良预后相关。在这里,我们研究了在接受免疫化疗的 FL 患者中,肿瘤血管生成是否与 MC 含量和结局相关。
使用 CD31、CD34 和肥大细胞 tryptase 抗体,从 95 例 FL 患者的预处理样本中通过免疫组织化学测定微血管密度(MVD)和 MC 含量。为了进行比较,分析了另一组 24 例 FL 患者的基因表达数据。所有患者均接受利妥昔单抗(R)和环磷酰胺-多柔比星-长春新碱-泼尼松(CHOP)化疗联合治疗。
增加的 CD31+MVD 与肿瘤浸润 MC 数量和 CD34+血管呈正相关,与结局呈负相关。CD31+MVD 低的患者总体生存率和无进展生存率显著提高。多变量分析表明,CD31+MVD 具有独立于滤泡性淋巴瘤预后指数的预后价值,但不具有 MC 含量的预后价值。与免疫组织化学数据一致,高 CD31/PECAM1 mRNA 水平与不良结局相关。相反,VEGF mRNA 表达对结局具有阳性预后影响。
在接受 R-CHOP 治疗的 FL 患者中,血管生成与 MC 含量和结局相关。