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血管内皮生长因子表达与皮肤黑色素瘤组织病理学参数的关联

Association of vascular endothelial growth factor expression with patohistological parameters of cutaneous melanoma.

作者信息

Gacević Milomir, Jović Milena, Zolotarevski Lidija, Stanojević Ivan, Novaković Marijan, Miller Karolina, Šuljagić Vesna, Mijušković Željko, Vojvodić Danilo

出版信息

Vojnosanit Pregl. 2016 May;73(5):449-57. doi: 10.2298/vsp140804027g.

Abstract

BACKGROUND/AIM: Melanoma is the most aggresive malignant tumor of the skin. Contradictory data was published on vascular endothelial growth factor (VGEF) in tumor samples and its role in skin melanoma progression and prognosis. The aim of this study was to investigate the significance of VEGF expression as a prognostic parameter in melanoma.

METHODS

The experimental group included 81 patients with primary skin melanomas treated from 2009 to 2013 at the Military Medical Academy, Belgrade. The control group included 20 patients with dysplastic and 20 with benign naevi. Stratification was done according to gender, age, clinical and patological stage, localization, histologic type, Clark's, Breslow, mitotic count, regression and ulceration, tumor infiltrating lymphocytes and metastatic spread.Immunohistochemical staining was performed on skin biopsies using DAKO anti-VEGF antibodies (Ab), LSAB+HRP, DAB and microvawe antigen (Ag) retrieval in DAKO pH 9.0 solution. For statistical data analysis was done with ANOVA, Bonferroni, Mann Whitney and Wilcox on test.

RESULTS

The mean intensity of VEGF staining was statistically significantly higher in melanomas than in benign or dysplastic naevi. Furthermore, the highest recorded values were in Ia and IV clinical stages. The majority of melanomas with high intensity of VEGF staining were in pT1a pathological stage. Melanomas with the highest mitotic count (> 6) had a significantly higher intensity of VEGF staining than those with < 2 mitoses. The higest intensity of staining was in melanomas without significant lymphocytic infiltrate and the lowest was in those with brisk lymphocytic infiltrate, thus a statistical difference was siginifant. The mean intensity of VEGF staining was highest in melanomas with lymphovascular invasion. There was no statistically significant difference between VEGF and any other parameter.

CONCLUSION

VEGF in primary skin melanomas plays an important role in tumor progression and is linked to the absence if tumor infiltrating lymphocytes and the presence of lymphovascular invasion. More detailed studies have to be done on VEGF prognostic value in melanoma on a larger number of patients.

摘要

背景/目的:黑色素瘤是皮肤最具侵袭性的恶性肿瘤。关于肿瘤样本中的血管内皮生长因子(VGEF)及其在皮肤黑色素瘤进展和预后中的作用,已发表了相互矛盾的数据。本研究的目的是探讨VEGF表达作为黑色素瘤预后参数的意义。

方法

实验组包括2009年至2013年在贝尔格莱德军事医学院接受治疗的81例原发性皮肤黑色素瘤患者。对照组包括20例发育异常痣患者和20例良性痣患者。根据性别、年龄、临床和病理分期、部位、组织学类型、克拉克分级、布雷斯洛厚度、有丝分裂计数、消退和溃疡、肿瘤浸润淋巴细胞和转移扩散进行分层。使用DAKO抗VEGF抗体(Ab)、LSAB + HRP、DAB和在DAKO pH 9.0溶液中的微血管抗原(Ag)检索对皮肤活检组织进行免疫组织化学染色。对于统计数据分析,采用方差分析、邦费罗尼检验、曼-惠特尼检验和威尔科克森检验。

结果

黑色素瘤中VEGF染色的平均强度在统计学上显著高于良性或发育异常痣。此外,记录到的最高值出现在Ia期和IV期临床阶段。VEGF染色强度高的大多数黑色素瘤处于pT¹a病理阶段。有丝分裂计数最高(> 6)的黑色素瘤VEGF染色强度明显高于有丝分裂数< 2的黑色素瘤。染色强度最高的是无明显淋巴细胞浸润的黑色素瘤,最低的是有活跃淋巴细胞浸润的黑色素瘤,因此存在统计学差异。VEGF染色的平均强度在有淋巴管浸润的黑色素瘤中最高。VEGF与任何其他参数之间均无统计学显著差异。

结论

原发性皮肤黑色素瘤中的VEGF在肿瘤进展中起重要作用,并且与缺乏肿瘤浸润淋巴细胞和存在淋巴管浸润有关。必须对更多患者的黑色素瘤中VEGF的预后价值进行更详细的研究。

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