喉癌淋巴结转移相关因子的Logistic多元分析

背景喉癌可导致患者声音嘶哑,呼吸困难,吞咽困难,喉癌患者出现淋巴结转移后,用一般的手术治疗及生物学治疗往往难以有效,研究喉癌转移的相关因素,寻找能够准确判断喉癌转移的分子标志物以及能够抑制喉癌浸润转移的生物制剂,成为喉癌研究的关键.目的研究基质金属蛋白酶-2,基质金属蛋白酶-9,CD44v6,PCNA,nm23,血管内皮生长因子,p53,Cath-D和E-cadherin与喉癌淋巴结转移的相关性,为喉癌的临床治疗提供有益的指导.设计以病理标本为研究对象的试验研究.对象原发喉癌的标本为哈尔滨医科大学附属第四医院耳鼻喉科2002-02/2003-11住院手术的患者,免疫组化试验由中山大学附属第三医院完成.干预用免疫组化方法检测70例喉癌标本中基质金属蛋白酶-2,基质金属蛋白酶-9,CD44v6,PCNA,血管内皮生长因子,Cath-D,E-cadherin,p53和nm23等的表达.采用Logistic逐步回归的方法对9项与喉癌淋巴结转移有关的指标进行筛选.主要观察指标基质金属蛋白酶-2,基质金属蛋白酶-9,CD44v6,PCNA,血管内皮生长因子,Cath-D,E-cadherin,p53和nm23在喉癌中的表达.结果喉癌中MMP-9表达阳性者,发生淋巴结转移的机率最高(Wald=10.3501,P＜0.05);nm23和E-cadherin表达阴性或低表达者发生淋巴结转移的机率高(Wald=6.1896和6.8632,P均＜0.05).结论喉癌组织中基质金属蛋白酶-9,E-cadherin和nm23的表达情况,可作为术前预测患者淋巴结转移的有效指标,也为预后科学干预提供参考价值.

Multivariate Logistic analysis of clinicopathologic factors related to lymph node metastasis of laryngeal cancer

BACKGROUND: Laryngeal cancer can cause hoarse voice, dyspnea, and dysphagia, for which common surgical approaches or biotherapy hardly results when nodal metastases are present. Identification of the factors associated with laryngeal cancer metastases is a crucial task in the study of the malignancy, as such a revelation may help establish molecular markers for accurate assessment of metastases and develop biological agents to restrain the invasion and metastases.OBJECTIVE:To study the association of MMP-2, MMP-9, CD44v6, PCNA,nm23, VEGF, p53, Cath-D and E-cadherin with the metastasis of laryngeal cancer so as to provide evidence for clinical treatment of laryngeal cancer.DESIGN: An experimental study ofclinical specimens.PARTICIPANTS: All specimens of primary laryngeal cancer were obtained from patients receiving surgical treatment in the Department of Otolaryngology,Fourth Affiliated Hospital of Harbin Medical University from February 2002 to November 2003. Immunohistochemical examination of the specimens was conducted in the Third Affiliated Hospital of Sun Yat-sen University.INTERVENTIONS: The expressions of MMP-2, MMP-9, CD44v6, PCNA,nm23, VEGF, p53, Cath-D and E-cadherin were examined immunohistochemically in the specimens from 70 patients of laryngeal cancer. Logistic stepwise regression model was used to analyze the influence of the 9 clinicopathologic factors on lymph node metastasis.MAIN OUTCOME MEASURES: The expressions of MMP-2, MMP-9,CD44v6, PCNA, nm23, VEGF, p53, Cath-D and E-cadherin in laryngeal cancer specimens.RESULTS: Using the established equation to estimate lymph node metastasis, the frequency of lymph node metastasis was highest in patients with positive MMP-9 expression(Wald = 10. 350 1, P ＜ 0.05) . Lower E-cadherin expression was accompanied by higher frequency of lymph node metastasis, and nm23 expression in patients with lymph node metastases was significantly decreased in comparison with patients without metastases (Wald=6.189 6 and 6. 863 2, P ＜0.05).CONCLUSION: The expressions of MMP-9, E-cadherin and nm23 are useful indicators for preoperative prediction of lymph node metastasis of laryngeal cancer and provide valuable information for prognostic evaluation of the interventions.