CAJ | 학술논문

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 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.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.
목적:초보탐토선형정서성배사(linearly patterned programmed cell necrosis,LPPCN)여흑색소류혈관생성적관계,병분석기림상병리의의,위항종류혈관생성치료심조신적사로급파점.방법:관찰68례인체흑색소류표본중LPPCN적형태학특점급분포특정;응용면역조직화학방법검측조직중CD105급TGFβ1단백적표체정황;동시진행CD31화PAS쌍중염색이관찰혈관생성의태(Vasculo genic mimicry,VM)적분포.결과:1)LPPCN재HE경하형태위일족포질농축、포핵심염적종류세포,정선형혹망상분포,68례환자중LPPCN양성솔위55.89%(38/68).2)혈관생성의태밀도(VMD)급CD105표기적미혈관밀도(microvessel density,MVD)재LPPCN양성조고우LPPCN음성조(P<0.05);차이자여LPPCN적밀도균정정상관.TGFβ1단백적양성표체솔재LPPCN양성조고우음성조,동시기재발생LPPCN적종류세포중적표체명현고우주위세포,차이균구유통계학의의(P<0.05);차TGFβ1양성표체지수여CD105표기적MVD정정상관.3)LPPCN여성별、년령、발생부위、유무류전、림파결전이급원처전이무관(P>0.05);이여종류대소、핵분렬상수목、Breslow후도밀절상관(P<0.05).Kaplan-Meier생존분석현시LPPCN양성조적생존솔저우LPPCN음성조,차이유통계학의의(P<0.05).결론:흑색소류중존재LPPCN차여혈관생성관계밀절,부분종류세포발생LPPCN가능위종류실질중VM급신생혈관적형성제공공간기출;연구LPPCN대판단환자적예후유일정적삼고개치.
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 expres-sion 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 tu-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 sig-nificant differences (P<0.05). VMD and MVD were positively-correlated with the density of LPPCN. The posi-tive expression of TGFβ1 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 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 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.