目的:初步探讨线形程序性坏死(linearly patterned 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TGFβ1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 genie 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。TGFβ1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TGFβ1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。
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 malignant melanoma specimens were analyzed to observe the distribution of LPPCN and to examine the expression of CD105 and TGFβ1 using immunohistochemistry. The distribution of vasculogenic mimicry (VM) was observed by immunohistochemical and histochemical double staining of CD31 and PAS. Results: (1) The tumor cells undergoing LPPCN were darkly stained in the H&E-stained sections and distributed in patterns of lines and networks. Of the 68 cases 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 CD105 in LPPCN-positive group were higher than those in LPPCN-negative group, with significant differences (P〈0.05). VMD and MVD were positively correlated with the density of LPPCN The positive expression of TGFβ1 in LPPCN-positive group was higher than that in LPPCN-negative group and its expression in the regions of LPPCN was obviously higher than that in circumambient tumor cells, with a significant difference (P〈0.05). The expression of TGFβ1 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 indicated poor prognosis. Conclusion: LPPCN exists in malignant melanoma and is associated with VM and angiogenesis. Some tumor cells undergoing LPPCN have a spacial foundation for VM and angiogenesis. LPPCN can