黑色素瘤中线形程序性坏死与血管生成及预后关系的初步探讨*

Pilot Study on the Relationship of LPPCN with Neovascularization and Prognosis of Melanoma

    摘要
  • 摘要: 目的：初步探讨线形程序性坏死（linearly patterne d programmed cell necrosis ，LPPCN ）与黑色素瘤血管生成的关系，并分析其临床病理意义，为抗肿瘤血管生成治疗寻找新的思路及靶点。方法：观察68例人体黑色素瘤标本中LPPCN 的形态学特点及分布特征；应用免疫组织化学方法检测组织中CD105 及TGF β 1 蛋白的表达情况；同时进行CD31和PAS 双重染色以观察血管生成拟态（Vasculo genic mimicry，VM）的分布。结果：1）LPPCN 在HE镜下形态为一簇胞质浓缩、胞核深染的肿瘤细胞，呈线形或网状分布，68例患者中LPPCN 阳性率为55.89%（38/68）。 2）血管生成拟态密度（VMD）及CD105 标记的微血管密度（microvessel density，MVD）在LPPCN 阳性组高于LPPCN 阴性组（P<0.05）；且二者与LPPCN 的密度均呈正相关。TGF β 1 蛋白的阳性表达率在LPPCN 阳性组高于阴性组，同时其在发生LPPCN 的肿瘤细胞中的表达明显高于周围细胞，差异均具有统计学意义（P<0.05）；且TGF β 1 阳性表达指数与CD105 标记的MVD呈正相关。3）LPPCN 与性别、年龄、发生部位、有无瘤栓、淋巴结转移及远处转移无关（P>0.05）；而与肿瘤大小、核分裂像数目、Breslow厚度密切相关（P<0.05）。 Kaplan-Meier 生存分析显示LPPCN 阳性组的生存率低于LPPCN 阴性组，差异有统计学意义（P<0.05）。 结论：黑色素瘤中存在LPPCN 且与血管生成关系密切，部分肿瘤细胞发生LPPCN 可能为肿瘤实质中VM及新生血管的形成提供空间基础；研究LPPCN 对判断患者的预后有一定的参考价值。

     

    Abstract: Objective:To study the relationship of LPPCN with neovascularization and to analyze its clini -copathologic significance, in an effort to find a new target for anti vascular therapies. Methods:Sixty-eight ma-lignant melanoma specimens were analyzed to observe the distribution of LPPCN and to examine the expression of CD 105 and TGF β 1 using immunohistochemistry. The distribution of vasculogenic mimicry (VM) was observed by immunohistochemical and histochemical double staining of CD31and PAS. Results: (1) The tu -mor cells undergoing LPPCN were darkly stained in the H&E-stained sections and distributed in patterns of lines and networks. Of the 68cases of melanoma,55.89% (38/68) were recognized as having LPPCN. (2) In malignant melanoma specimens, the rate of vasculogenic mimicry density (VMD) and microvessel density (MVD) labeled by CD 105 in LPPCN-positive group were higher than those in LPPCN-negative group, with sig-nificant differences (P<0.05). VMD and MVD were positively correlated with the density of LPPCN. The positive expression of TGF β 1 in LPPCN-positive group was higher than that in LPPCN-negative group and its ex -pression in the regions of LPPCN was obviously higher than that in circumambient tumor cells, with a signifi-cant difference (P<0.05). The expression of TGF β 1 was positively correlated with MVD labeled by CD105 . ( 3)There was no relationship between LPPCN and gender, age, site, tumor embolus, lymph node metastasis or distant metastasis ( P>0.05), but LPPCN was correlated with tumor size, mitosis figure count and Breslow depth (P<0.05). Kaplan-Meier survival analysis showed the survival rate of patients with LPPCN was lower than that of patients without LPPCN, with a statistical significance (P<0.05). The presence of LPPCN indicat-ed poor prognosis. Conclusion:LPPCN exists in malignant melanoma and is associated with VM and angio-genesis. Some tumor cells undergoing LPPCN have a spacial foundation for VM and angiogenesis. LPPCN can be an index for the evaluation of the prognosis of melanoma patients.

     

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