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[喉癌与血管生成]

[Laryngeal cancer and angiogenesis].

作者信息

Beatrice F, Valente G, Cammarota R, Bisciari T, Ragona R, Giusti U, Bussolino F, Sartoris A

机构信息

Dipartimento di Fisiopatologia Clinica, Università di Torino.

出版信息

Acta Otorhinolaryngol Ital. 1996 Aug;16(4):355-62.

PMID:9082830
Abstract

Angiogenesis is required for the growth of solid tumors which, in avascular condition, are limited to 2-3 mm3 volume. The switch to the angiogenic phenotype allows new vessels to converge upon the tumor, growth to proceed at an exponential rate and metastasis diffusion. The evaluation of tumoral angiogenesis has been proposed to be an independent prognostic marker of behaviour of some solid tumors: it has been demonstrated that, in some types of carcinoma (breast, prostate, lung, etc...), an intense vascular proliferation correlates with the aggressiveness of the disease. However in malignant melanomas and colorectal carcinomas, there are conflicting results on the correlation between angiogenesis and the progression of the cancer. There are also conflicting data on the role of microvessels count (MC) in the management of head and neck cancer. Despite a large number of studies, at the present, there are not biological or molecular markers available to predict consistently the outcome of the patients with laryngeal squamous cell carcinoma (LSCC). In fact the prognosis of this tumor has been mainly based, up to now, on a number of clinico-pathological parameters, especially localization, tumor extent and nodal involvement. The aim of this study has been to compare MC inside LSCC with disease free survival, grading, pT, pN and pathological stage. We investigated the relevance of the number of microvessels in the peritumoral stroma of 68 LSCC (only Caucasian males, age 35-70 years), classified according to UICC/1987 randomly selected (33 classified in clinical stage I e II and 35 in clinical stage III-IV). All patients have been surgically treated and pN + cases have been also submitted to radiotherapy. The follow-up was 60-84 months. The vascular density was assessed according to Horak et Al. with an immunohistochemical method using JC70 monoclonal antibody (CD31; Dako, Astrup, Denmark). Univariate analysis showed that MC, pT, pN, Pathological Stage and grading were correlated with the disease-free survival. A MC < 120/mm2 was predictive for a high survival index; in contrast a MC > 150 mm2 were associated with relapse. Furthermore, multivariate analysis demonstrated that MC was the only independent predictor for the disease free survival. Our findings demonstrate that in LSCC, MC is the first measurable biological parameter which is significant for evaluating the disease free-survival. Therefore, MC in LSCC is crucial in the prognosis and in the choice of a more aggressive management of the disease, including the possible treatment with antiangiogenic compound.

摘要

实体瘤的生长需要血管生成,在无血管状态下,实体瘤体积限于2 - 3立方毫米。向血管生成表型的转变使新血管向肿瘤汇聚,肿瘤得以呈指数级生长并发生转移扩散。肿瘤血管生成的评估已被认为是一些实体瘤行为的独立预后标志物:已证实,在某些类型的癌(乳腺癌、前列腺癌、肺癌等)中,强烈的血管增殖与疾病的侵袭性相关。然而,在恶性黑色素瘤和结直肠癌中,血管生成与癌症进展之间的相关性存在相互矛盾的结果。关于微血管计数(MC)在头颈部癌治疗中的作用也存在相互矛盾的数据。尽管进行了大量研究,但目前尚无生物学或分子标志物可始终如一地预测喉鳞状细胞癌(LSCC)患者的预后。事实上,到目前为止,该肿瘤的预后主要基于一些临床病理参数,尤其是肿瘤定位、范围和淋巴结受累情况。本研究的目的是比较LSCC内部的MC与无病生存期、分级、pT、pN和病理分期。我们调查了68例LSCC(仅白种男性,年龄35 - 70岁)瘤周基质中微血管数量的相关性,这些病例根据UICC/1987随机分类(33例为临床I期和II期,35例为临床III - IV期)。所有患者均接受了手术治疗,pN + 病例还接受了放疗。随访时间为60 - 84个月。根据霍拉克等人的方法,使用JC�0单克隆抗体(CD31;丹麦达科公司阿斯楚普产品)通过免疫组织化学方法评估血管密度。单因素分析表明,MC、pT、pN、病理分期和分级与无病生存期相关。MC < 120/mm²可预测高生存指数;相反,MC > 150/mm²与复发相关。此外,多因素分析表明,MC是无病生存期的唯一独立预测因子。我们的研究结果表明,在LSCC中,MC是第一个可测量的对评估无病生存期有意义的生物学参数。因此,LSCC中的MC对预后以及选择更积极的疾病治疗方案(包括可能使用抗血管生成化合物进行治疗)至关重要。

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