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血管生成和宿主免疫反应有助于解释肾移植受者中非黑素瘤皮肤癌的侵袭性特征。

Angiogenesis and host immune response contribute to the aggressive character of non-melanoma skin cancers in renal transplant recipients.

机构信息

Angiogenesis and Cancer Research Group, University of Otago Christchurch, Christchurch, New Zealand.

出版信息

Histopathology. 2011 May;58(6):875-85. doi: 10.1111/j.1365-2559.2011.03845.x.

Abstract

AIMS

The aim of this study was to determine the contribution of tumour angiogenesis to the aggressive growth of non-melanoma skin cancers (NMSCs) in renal transplant recipients (RTRs).

METHODS AND RESULTS

The study cohort included RTRs (n = 38) with formalin-fixed paraffin-embedded tumour samples available from first post-transplant NMSC (NMSC1) surgically excised at Christchurch Hospital, New Zealand, from 1997 to 2007. Comparable samples excised from immunocompetent individuals (ICIs) (n = 36) were selected to accommodate confounding factors. Markers of tumour angiogenesis were evaluated by immunohistochemistry, and analysed for associations with clinicopathological variables. As compared with ICIs, RTRs had a higher proportion of tumours with high microvessel density (P = 0.008), high proliferating capillary index (P < 0.0001) and low microvessel pericyte coverage index (P < 0.0001), and RTRs had a shorter cumulative second NMSC (NMSC2)-free interval (P < 0.0001). ICIs had a higher proportion of tumours with a 'marked' number of vascular endothelial growth factor (VEGF)-A-positive leukocytes than RTRs (P = 0.04), and RTRs with a 'moderate/marked' number of VEGF-A-positive leukocytes had longer cumulative NMSC2-free intervals than those with a 'minimum' number (P = 0.02).

CONCLUSIONS

This study demonstrates increased tumour angiogenesis in NMSC in RTRs, and suggests a role for VEGF-A-positive peritumoural leukocytes in suppressing NMSC development.

摘要

目的

本研究旨在确定肿瘤血管生成对肾移植受者(RTR)中非黑素瘤皮肤癌(NMSC)侵袭性生长的贡献。

方法和结果

该研究队列包括 38 例 RTR,他们在新西兰克赖斯特彻奇医院接受了首次移植后 NMSC(NMSC1)的手术切除,可获得福尔马林固定石蜡包埋的肿瘤样本,时间为 1997 年至 2007 年。选择了来自免疫功能正常个体(ICIs)的可比样本(n=36)以适应混杂因素。通过免疫组织化学评估肿瘤血管生成标志物,并分析其与临床病理变量的关系。与 ICIs 相比,RTR 中具有高微血管密度(P=0.008)、高增殖毛细血管指数(P<0.0001)和低微血管周细胞覆盖率指数(P<0.0001)的肿瘤比例更高,并且 RTR 的累积第二次 NMSC(NMSC2)无间隔时间更短(P<0.0001)。ICIs 中具有“大量”血管内皮生长因子(VEGF)-A 阳性白细胞的肿瘤比例高于 RTR(P=0.04),具有“中度/大量”VEGF-A 阳性白细胞的 RTR 具有比具有“最小”数量的更长的累积 NMSC2 无间隔时间(P=0.02)。

结论

本研究表明 RTR 中 NMSC 的肿瘤血管生成增加,并表明肿瘤周围 VEGF-A 阳性白细胞在抑制 NMSC 发展中起作用。

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