Mitsudomi T, Oyama T, Nishida K, Ogami A, Osaki T, Sugio K, Yasumoto K, Sugimachi K, Gazdar A F
Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka 812-82, Japan.
Clin Cancer Res. 1996 Jul;2(7):1185-9.
We examined 110 patients with non-small cell lung cancer who underwent consecutive pulmonary resection for loss of heterozygosity (LOH) at the short arm of chromosome 3 (3p). We performed a PCR-based microsatellite polymorphism analysis for detection of LOH. The microsatellite markers used were D3S966 (3p21.3), D3S1007 (3p21. 3-22), and D3S1228 (3p14.1-14.3). Of 98 informative cases, 3p LOH was found in 45 (46%). 3p LOH was more prevalent in squamous cell carcinoma (24/35, 69%) than in adenocarcinoma (18/52, 35%; P = 0.0019). There was no significant association between 3p LOH and sex, disease stage, or grade of differentiation. However, patients with 3p LOH tended to survive for a shorter period of time (P = 0.0631, log rank test). There was no such tendency in squamous cell carcinoma (P = 0.7513), but in adenocarcinoma, the difference of survival was significant (P = 0.0015). Cox's proportional hazards model also predicted that 3p LOH was an independent poor prognostic marker in adenocarcinoma (P = 0.0502) but not in squamous cell carcinoma or in the entire cohort (P = 0.7866 and 0.1371, respectively). LOH at 3p may help to identify non-small cell lung cancer patients with a poor prognosis, who thus need an intensive postoperative follow-up protocol or who are suitable for novel investigational therapeutic approaches. It is also suggested that the putative tumor suppressor gene at 3p may have a different role in squamous cell carcinoma and adenocarcinoma of the lung.
我们对110例接受连续性肺切除术的非小细胞肺癌患者进行了研究，检测其3号染色体短臂（3p）的杂合性缺失（LOH）。我们采用基于聚合酶链反应（PCR）的微卫星多态性分析来检测LOH。所使用的微卫星标记为D3S966（3p21.3）、D3S1007（3p21.3 - 22）和D3S1228（3p14.1 - 14.3）。在98例信息充分的病例中，45例（46%）发现有3p LOH。3p LOH在鳞状细胞癌中（24/35，69%）比在腺癌中（18/52，35%）更常见（P = 0.0019）。3p LOH与性别、疾病分期或分化程度之间无显著关联。然而，有3p LOH的患者生存时间往往较短（P = 0.0631，对数秩检验）。在鳞状细胞癌中无此趋势（P = 0.7513），但在腺癌中，生存差异显著（P = 0.0015）。Cox比例风险模型也预测，3p LOH在腺癌中是独立的不良预后标志物（P = 0.0502），但在鳞状细胞癌或整个队列中并非如此（分别为P = 0.7866和0.1371）。3p处的LOH可能有助于识别预后不良的非小细胞肺癌患者，这些患者因此需要强化的术后随访方案或适合新的研究性治疗方法。还提示3p处假定的肿瘤抑制基因在肺鳞状细胞癌和腺癌中可能具有不同作用。
