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肾移植和免疫功能正常人群中非黑色素瘤皮肤癌的独特免疫组织化学表型。

Distinct immunohistochemical phenotype of nonmelanoma skin cancers between renal transplant and immunocompetent populations.

机构信息

Department of Nephrology and Renal Transplantation, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain.

出版信息

Transplantation. 2010 Nov 15;90(9):986-92. doi: 10.1097/TP.0b013e3181f6a0a1.

Abstract

BACKGROUND

Nonmelanoma skin cancers (NMSCs), the most common malignancy in kidney transplant recipients (KTRs), are more frequent and aggressive in KTR than in the general population. These phenomena could be caused by immunosuppressive treatments, both by decreasing immunosurveillance and by a direct oncogenic potential.

METHODS

To assess the possible mechanisms involved in the clinical behavior of NMSC in KTR, we compared the tumoral expression of several molecule markers between 106 NMSC (basal cell carcinoma [BCC]; n=55, squamous cell carcinoma [SCC]; n=51) collected from 37 KTR and 51 control patients (CPs) from the general population. Immunohistochemical expression of transforming growth factor beta 1, epidermal growth factor receptor, protein 53 (p53), phospho-p70-S6-kinase, mammalian target of rapamycin (mTOR), and phospho-mTOR (Ser2448) were compared between KTR and CP and were also correlated with immunosuppressive therapy.

RESULTS

p53 expression and transforming growth factor beta intensity were greater in SCC from KTR than from CP. In contrast, phospho-mTOR and phospho-p70S6K (Thr421Ser424) expressions were higher in SCC from CP. p53 and phospho-p70S6K (Thr389) expression were higher in BCC from KTR than from CP. Expression of the other biological markers showed no statistically significant differences between SCC and BCC from KTR treated with or without calcineurin inhibitors.

CONCLUSIONS

Several prooncogenic markers showed distinct patterns of expression in NMSC from KTR. These differential characteristics could be responsible for the clinical behavior of posttransplantation NMSC. Furthermore, these markers may constitute possible targets for future therapeutic approaches to NMSC in KTR and could help to guide immunosuppressive therapy.

摘要

背景

非黑色素瘤皮肤癌(NMSC)是肾移植受者(KTR)中最常见的恶性肿瘤,其在 KTR 中的发生频率和侵袭性均高于普通人群。这些现象可能是由免疫抑制治疗引起的,既降低了免疫监视,又具有直接致癌潜能。

方法

为了评估 KTR 中 NMSC 临床行为中涉及的可能机制,我们比较了 37 例 KTR 和 51 例来自普通人群的对照患者(CP)中 106 例 NMSC(基底细胞癌 [BCC];n=55,鳞状细胞癌 [SCC];n=51)的几种分子标志物的肿瘤表达。比较了 KTR 和 CP 之间转化生长因子β 1、表皮生长因子受体、蛋白 53(p53)、磷酸化 p70-S6-激酶、哺乳动物雷帕霉素靶蛋白(mTOR)和磷酸化 mTOR(Ser2448)的免疫组织化学表达,并与免疫抑制治疗进行了相关性分析。

结果

与 CP 相比,KTR 中 SCC 的 p53 表达和转化生长因子β强度更高。相比之下,CP 中 SCC 的磷酸化 mTOR 和磷酸化 p70S6K(Thr421Ser424)表达更高。KTR 中 BCC 的 p53 和磷酸化 p70S6K(Thr389)表达高于 CP。在未接受钙调神经磷酸酶抑制剂治疗或接受钙调神经磷酸酶抑制剂治疗的 KTR 中,SCC 和 BCC 的其他生物标志物表达无统计学差异。

结论

KTR 中 NMSC 的几种促癌标志物表现出不同的表达模式。这些差异特征可能是移植后 NMSC 临床行为的原因。此外,这些标志物可能成为未来 KTR 中 NMSC 治疗方法的潜在靶点,并有助于指导免疫抑制治疗。

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