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肿瘤相关的微血管生成和淋巴管生成是否可作为 Xp11.2 易位性肾细胞癌患者的新型预后因素?

Are tumor-associated micro-angiogenesis and lymphangiogenesis considered as the novel prognostic factors for patients with Xp11.2 translocation renal cell carcinoma?

机构信息

Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, Jiangsu Province, People's Republic of China, 210008.

Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.

出版信息

BMC Cancer. 2020 Dec 2;20(1):1182. doi: 10.1186/s12885-020-07696-2.

DOI:10.1186/s12885-020-07696-2
PMID:33267784
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7709278/
Abstract

BACKGROUND

Tumor micro-angiogenesis and lymphangiogenesis are effective prognostic predictors in many solid malignancies. However, its role on Xp11.2 translocation RCC has not been fully elucidated. Herein, we purposed to explore the correlation between quantitative parameters of tumor-related micro-angiogenesis or lymphangiogenesis and the prognosis of Xp11.2 translocation renal cell carcinoma (Xp11.2 translocation RCC).

METHODS

Tissue samples were obtained from 34 Xp11.2 translocation RCC and 77 clear cell renal cell carcinoma (ccRCC) between January 2007 and December 2018. Micro-angiogenesis was detected using CD34 antibody and quantified with microvessel density (MVD) and microvessel area (MVA), while the lymphangiogenesis in RCC was immunostained with D2-40 antibody and assessed using lymphatic vessel density (LVD) and lymphatic vessel area (LVA). The Kaplan-Meier method of survival analysis was used to estimate prognosis, and both univariate and multivariate analysis was performing using the Cox proportional hazards.

RESULTS

The MVD and MVA of Xp11.2 translocation RCC in two detected areas (intratumoral and peritumoral area) were not significantly different from that of ccRCC (all P > 0.05). Notably, D2-40-positive lymphatic vessels of Xp11.2 translocation RCC were highly detected in the peritumoral area compared to the intratumoral area. Interestingly, the peritumoral LVD and LVA of Xp11.2 translocation RCC were higher than that of ccRCC (all P < 0.05). Furthermore, both intratumoral MVD or MVA and peritumoral LVD or LVA were significantly associated with pT stage, pN stage, cM stage, AJCC stage, and WHO/ISUP grade (all P < 0.05). Univariate analysis of Cancer-specific survival (CSS) revealed that CSS was substantially longer in patients with low intratumoral MVD or MVA than in patients with high intratumoral MVD or MVA (P = 0.005 and P = 0.001, respectively). Lastly, the Cox proportional hazards model in CSS demonstrated that both intratumoral MVD or MVA and peritumoral LVD or LVA were not independent prognostic parameters (all P > 0.05).

CONCLUSIONS

This study outlines that Xp11.2 translocation RCC is a highly vascularized solid RCC, characterized by rich lymph vessels in the peritumoral area. Quantitative parameters of micro-angiogenesis and lymphangiogenesis could not be considered as novel prognostic factors for patients with xp11.2 translocation RCC.

摘要

背景

肿瘤微血管生成和淋巴管生成是许多实体恶性肿瘤有效的预后预测指标。然而,其在 Xp11.2 易位肾细胞癌(Xp11.2 易位 RCC)中的作用尚未完全阐明。在此,我们旨在探讨肿瘤相关微血管生成或淋巴管生成的定量参数与 Xp11.2 易位肾细胞癌(Xp11.2 易位 RCC)预后之间的相关性。

方法

本研究纳入了 2007 年 1 月至 2018 年 12 月期间的 34 例 Xp11.2 易位 RCC 和 77 例透明细胞肾细胞癌(ccRCC)患者的组织样本。使用 CD34 抗体检测微血管生成,并通过微血管密度(MVD)和微血管面积(MVA)进行定量,同时使用 D2-40 抗体对 RCC 中的淋巴管生成进行免疫染色,并通过淋巴管密度(LVD)和淋巴管面积(LVA)进行评估。采用 Kaplan-Meier 生存分析法估计预后,采用单因素和多因素 Cox 比例风险模型进行分析。

结果

Xp11.2 易位 RCC 在两个检测区域(肿瘤内和肿瘤旁区域)的 MVD 和 MVA 与 ccRCC 无显著差异(均 P>0.05)。值得注意的是,Xp11.2 易位 RCC 的 D2-40 阳性淋巴管在肿瘤旁区域的检出率明显高于肿瘤内区域。有趣的是,Xp11.2 易位 RCC 的肿瘤旁 LVD 和 LVA 高于 ccRCC(均 P<0.05)。此外,肿瘤内 MVD 或 MVA 以及肿瘤旁 LVD 或 LVA 均与 pT 分期、pN 分期、cM 分期、AJCC 分期和 WHO/ISUP 分级显著相关(均 P<0.05)。肿瘤特异性生存(CSS)的单因素分析显示,肿瘤内 MVD 或 MVA 低的患者 CSS 明显长于肿瘤内 MVD 或 MVA 高的患者(P=0.005 和 P=0.001)。最后,CSS 的 Cox 比例风险模型显示,肿瘤内 MVD 或 MVA 以及肿瘤旁 LVD 或 LVA 均不是独立的预后参数(均 P>0.05)。

结论

本研究表明,Xp11.2 易位 RCC 是一种高度血管化的实体瘤,其特点是肿瘤旁区域富含淋巴管。微血管生成和淋巴管生成的定量参数不能作为 Xp11.2 易位 RCC 患者的新型预后因素。

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