Kakolyris S, Giatromanolaki A, Koukourakis M, Kaklamanis L, Kouroussis C H, Bozionelou V, Georgoulias V, Gatter K C, Harris A L
Department of Clinical Oncology, University Hospital, Heraklion, Crete, Greece.
Anticancer Res. 2001 Nov-Dec;21(6B):4311-6.
LH39, is a monoclonal antibody recognizing an epitope located at the lamina lucida of mature small veins and capillaries but not in newly- formed vessels of several pathological conditions including cancer. We examined the ratio of mature/immature vessels in 50 breast and 81 lung carcinomas and correlated the vascular maturation index (VMI) to different clinicopathological variables including angiogenesis. Mature vessels were defined by staining with antibodies to both LH39 and CD31, using double immunohistochemistry, whereas immature vessels stained only for CD31. VMI was defined as the percentage fraction of mature vessels (LH39 positive)/total number of vessels (CD31 positive). VMI in breast carcinomas ranged from 0-47% (median 8.75%), which was significantly lower than that observed in the normal breast cases (range 54%-70%; median 68%). The median VMI in the non-small cell lung carcinomas was 46% (range 15%-90%). There was a significant inverse correlation between high tumor VMI and absence of nodal involvement in both breast and lung tumors examined (p=0.01). Thymidine phosphorylase (TP) expression, but not vascular endothelial growth factor (VEGF) expression, was related to a low VMI showing an intense vascular remodeling in TP expressing cases. Thus, assessment of vessel maturation might be complementary to microvessel number to aid the identification of patients who might benefit from specific antiangiogenic therapies or vascular targeting treatment.
LH39是一种单克隆抗体,可识别位于成熟小静脉和毛细血管透明板的一个表位,但在包括癌症在内的几种病理状况的新生血管中不表达。我们检测了50例乳腺癌和81例肺癌中成熟/不成熟血管的比例,并将血管成熟指数(VMI)与包括血管生成在内的不同临床病理变量相关联。使用双重免疫组织化学法,通过用抗LH39和抗CD31抗体染色来定义成熟血管,而不成熟血管仅对CD31染色呈阳性。VMI定义为成熟血管(LH39阳性)占血管总数(CD31阳性)的百分比。乳腺癌中的VMI范围为0 - 47%(中位数8.75%),显著低于正常乳腺病例(范围54% - 70%;中位数68%)。非小细胞肺癌中的VMI中位数为46%(范围15% - 90%)。在所检测的乳腺癌和肺癌中,高肿瘤VMI与无淋巴结转移之间存在显著负相关(p = 0.01)。胸苷磷酸化酶(TP)表达而非血管内皮生长因子(VEGF)表达与低VMI相关,在表达TP的病例中显示出强烈的血管重塑。因此,评估血管成熟可能是微血管数量评估的补充,有助于识别可能从特定抗血管生成疗法或血管靶向治疗中获益的患者。