Pigment Cell Center, Iyengar Farm, New Delhi, 110037, India.
Pathol Oncol Res. 2011 Sep;17(3):569-77. doi: 10.1007/s12253-010-9350-y. Epub 2011 Jan 4.
The relationship of vasculogenic mimicry to pigment in nodular vertical growth phase [VGP] cutaneous melanomas is assessed in this study. 10 nodules each from 27 tumors, 15 pigmented and 12 amelanotic were sampled in proportion to the pigment level. Serial frozen and paraffin sections subjected to HE, Reticulin, PAS to assess the vascular pattern; Dopa Oxidase and Immunopositivity for HMB45, LN5 [laminin 5] & integrin[α(5)β(1)], and EM [electron microscopy] to identify Weibel-Palade bodies within endothelial cells. The vascular pattern, pigment and the immunopositivity was mapped to assess the percentage VM [vasculogenic sinusoids] vs INC [incorporated microvasculature]. In pigmented melanomas, INC from pre-existing stromal vessels is predominant. Amelanotic melanomas show embryonic vasculogenic mimicry, a self-propagating system of spaces within the sheets of tumors cells. Both INC and VM co-exist in tumors with both amelanotic and melanotic nodules. In areas with VM, loci of LN5 and α(5)β(1) integrin positive cells appear within the proliferating columns, positivity in these cells suggesting a switch to a more aggressive form. Irregular spaces appear lined by tumor cells, with initial hemopoeitic activity, coalesce and interlink into tubular networks. Spaces lined by tumor cells extend into an intricate network which then connects with the angiogenetic system. The tumor cells lining the vasculogenic spaces are positive for LN5, α(5)β(1) integrin. Statistically, INC is significantly higher in pigmented melanomas, whereas amelanotic melanomas show significantly higher VM. Pigmentation is correlated positively with INC and negatively with VM. INC and VM are negatively correlated with each other.
本研究评估了血管生成拟态与结节性垂直生长期(VGP)皮肤黑色素瘤中色素的关系。根据色素水平,从 27 个肿瘤的每个肿瘤中各取 10 个结节,其中 15 个为色素性,12 个为无色素性。对连续的冷冻和石蜡切片进行 HE、网状纤维、PAS 染色以评估血管模式;多巴氧化酶和 HMB45、LN5(层粘连蛋白 5)和整合素[α(5)β(1)]免疫染色以识别内皮细胞中的 Weibel-Palade 小体;通过 EM(电子显微镜)识别内皮细胞中的 Weibel-Palade 小体。绘制血管模式、色素和免疫染色图,以评估血管生成窦(VM)与内皮层整合的微血管(INC)的百分比。在色素性黑色素瘤中,INC 主要来源于预先存在的基质血管。无色素性黑色素瘤显示出胚胎血管生成拟态,即肿瘤细胞片内的自我增殖的空间系统。无色素性和色素性结节均存在的肿瘤中同时存在 INC 和 VM。在 VM 存在的区域,LN5 和α(5)β(1)整合素阳性细胞位于增殖柱内,这些细胞的阳性表达提示向更具侵袭性的形式转变。不规则的空间被肿瘤细胞排列,最初具有造血活性,融合并相互连接形成管状网络。肿瘤细胞排列的空间延伸到复杂的网络,然后与血管生成系统相连。血管生成空间的肿瘤细胞呈 LN5、α(5)β(1)整合素阳性。统计分析显示,色素性黑色素瘤中 INC 显著更高,而无色素性黑色素瘤中 VM 显著更高。色素沉着与 INC 呈正相关,与 VM 呈负相关。INC 和 VM 之间呈负相关。