Is downregulation of MHC class I antigen expression in human non-small cell lung cancer associated with prolonged survival?
Is downregulation of MHC class I antigen expression in human non-small cell lung cancer associated with prolonged survival?
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DOI：
10.1007/s00262-005-0085-7
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发表时间：
2006-08-01
影响因子：
5.8
通讯作者：
Ferrone, S
中科院分区：
文献类型：
--
作者：
Ramnath, N;Tan, D;Ferrone, S
目的：研究HLA I类抗原在非小细胞肺癌（NSCLC）病变中的表达特征，并探讨这些分子下调的临床意义。方法：用HLAⅰ类重链特异性单抗HC-10对190例初代福尔马林固定石蜡包埋的NSCLC病变进行染色。结果以染色肿瘤细胞的百分比进行评分，并分为3组：0-24%（阴性），25-75%（异质性）和> 75%（阳性）。HLA I类抗原表达与进展时间和生存的临床和病理预测因子相关，并使用卡方检验进行分析。在控制混杂因素的情况下，使用Cox回归模型评估HLA I类抗原表达与生存之间的关系。结果：原发性NSCLC病变中HLA I类抗原表达阴性153例，异质表达25例，阳性12例。与生存率显著相关的独立变量包括肿瘤分期、PS和体重减轻。HLA I类抗原表达阴性、异质性和阳性患者的中位生存时间分别为40.6个月、44.0个月和17.9个月。结论：HLA I类抗原缺陷在非小细胞肺癌病变中发生率较高（93.6%）。HLA I类抗原下调与生存率的提高相关，尽管这种关联没有统计学意义。这些结果与葡萄膜黑色素瘤和乳腺癌的相似发现相似，提高了NK细胞可能在控制非小细胞肺癌肿瘤中发挥作用的可能性。
Purpose: To characterize HLA class I antigen expression in non-small cell lung cancer (NSCLC) lesions, and to assess the clinical significance of these molecules' downregulation. Methods: One hundred and ninety primary formalin fixed, paraffin embedded NSCLC lesions were stained with HLA class I heavy chain-specific mAb HC-10. Results were scored as percentage of stained tumor cells and categorized into three groups: 0-24% (negative), 25-75% (heterogeneous) and > 75% (positive). HLA class I antigen expression was correlated with clinical and pathologic predictors of time to progression and survival and analyzed using the chi-square test. Association between HLA class I antigen expression and survival was assessed using Cox regression models, while controlling for confounders. Results: HLA class I antigen expression was negative, heterogeneous and positive in 153, 25 and 12 primary NSCLC lesions, respectively. Independent variables significantly associated with survival included tumor stage, PS and weight loss. The median survival times were 40.6, 44.0 and 17.9 months for patients with a HLA class I antigen expression scored as negative, heterogeneous and positive, respectively. Conclusion: HLA class I antigen defects were found with high frequency (93.6%) in NSCLC lesions. HLA class I antigen downregulation was associated with improved survival, although this association was not statistically significant. These results, which parallel similar findings in uveal melanoma and in breast carcinoma, raise the possibility that NK cells may play a role in the control of NSCLC tumors.