Komaki R, Fujii T, Perkins P, Ro J Y, Allen P K, Mason K A, Mountain C F, Milas L
Department of Radiotherapy, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Int J Radiat Oncol Biol Phys. 1996 Oct 1;36(3):601-5. doi: 10.1016/s0360-3016(96)00351-3.
This study aimed to established whether spontaneous apoptosis or mitosis has prognostic value among patients with pathologically staged N1 nonsmall cell lung carcinoma (NSCLC) treated with surgical resection with or without adjuvant therapy.
Material from 173 patients who had resections between 1970 and 1988 was analyzed for apoptosis and mitosis. There were 128 men and 45 women, with a median age of 61 years. There were 86 squamous cell carcinomas (SQ), 73 adenocarcinomas (AC), 3 large-cell carcinomas (LC), 6 SQ-AC, and 5 unclassified. Patients were observed from 2 to 209 months (median 27). Actuarial methods were used to assess survival and freedom from distant metastasis.
In NSCLC, apoptosis was found to range from 0.2% to 2.8% (median 1.0%) and mitosis from 0 to 1.8% (median 0.4%). Tumors having higher levels of apoptosis also had higher levels of mitosis (p = 0.001). The values of neither apoptosis nor mitosis depended on size, location, differentiation of tumors, age, performance status, or weight loss of patients. However, the values of apoptosis depended on tumor histology in that high values (greater than or equal to the median) were more frequent in SQ (49%) than in AC/LC (29%) (p = 0.01). The overall survival for NSCLC patients, which was 33% at 5 years, did not depend on the level of either apoptosis or mitosis. The 5-year survival of patients having SQ was higher (43%) than that of patients having AC/LC (21%) (p = 0.03). Patients with high apoptosis showed significantly better 5-year overall (p = 0.008) and DMF (p = 0.0012) survivals in the SQ group compared to the AC/LC group. High mitosis compared to low mitosis was a significantly better predictor for 5-year survival (62% vs. 29%, respectively) (p = 0.035) in the SQ. However, high mitosis was a significantly worse 5-year DMF survival predictor compared to low mitosis: 13% vs. 56%, respectively (p = 0.05) in AC/LC. In the multivariate models for AC/LC, mitosis remained a significant predictor of 5-year distant metastasis (p = 0.025) controlling for treatment groups (p = 0.042), whereas apoptosis was an independently significant predictor of 5-year distant metastasis (p = 0.010).
Squamous cell histology predicted significantly better 5-year overall and DMF survivals compared to AC/LC. Apoptosis was correlated with mitosis. Although apoptosis or mitosis did not predict survival or DM, high apoptosis or mitosis predicted significantly better survival in SQ and significantly worse survival in AC/LC with regard to overall and DMF survivals. In the multivariate models for AC/LC, apoptosis alone or mitosis with variable treatment was a significant predictor of 5-year distant metastasis. Thus, pretreatment levels of apoptosis or mitosis might be useful for predicting treatment outcome of SQ and AC/LC subsets of NSCLC when analyzed separately and for predicting metastatic incidence of AC/LC.
本研究旨在确定在接受手术切除联合或不联合辅助治疗的病理分期为N1的非小细胞肺癌（NSCLC）患者中，自发凋亡或有丝分裂是否具有预后价值。
分析了1970年至1988年间173例接受手术切除患者的材料中的凋亡和有丝分裂情况。其中男性128例，女性45例，中位年龄61岁。有86例鳞状细胞癌（SQ）、73例腺癌（AC）、3例大细胞癌（LC）、6例SQ-AC和5例未分类肿瘤。对患者进行了2至209个月（中位27个月）的观察。采用精算方法评估生存率和无远处转移情况。
在NSCLC中，凋亡率为0.2%至2.8%（中位值1.0%），有丝分裂率为0至1.8%（中位值0.4%）。凋亡水平较高的肿瘤，其有丝分裂水平也较高（p = 0.001）。凋亡和有丝分裂的值均不取决于肿瘤的大小、位置、分化程度、患者年龄、体能状态或体重减轻情况。然而，凋亡值取决于肿瘤组织学类型，即高值（大于或等于中位值）在SQ中更常见（49%），而在AC/LC中为29%（p = 0.01）。NSCLC患者的总生存率在5年时为33%，不取决于凋亡或有丝分裂水平。SQ患者的5年生存率较高（43%），高于AC/LC患者（21%）（p = 0.03）。与AC/LC组相比，高凋亡的SQ组患者5年总生存率（p = 0.008）和无远处转移生存率（DMF，p = 0.0012）显著更好。在SQ中，高有丝分裂与低有丝分裂相比，是5年生存率的显著更好预测指标（分别为62%和29%）（p = 0.035）。然而，在AC/LC中，高有丝分裂与低有丝分裂相比，是5年DMF生存率的显著更差预测指标：分别为13%和56%（p = 0.05）。在AC/LC的多变量模型中，有丝分裂仍然是5年远处转移的显著预测指标（p = 0.025），同时控制了治疗组（p = 0.042），而凋亡是5年远处转移的独立显著预测指标（p = 0.010）。
与AC/LC相比，鳞状细胞组织学类型预测的5年总生存率和DMF生存率显著更好。凋亡与有丝分裂相关。虽然凋亡或有丝分裂不能预测生存率或远处转移，但就总生存率和DMF生存率而言，高凋亡或有丝分裂在SQ中预测生存率显著更好，在AC/LC中预测生存率显著更差。在AC/LC的多变量模型中，单独的凋亡或有丝分裂与不同治疗方法一起是5年远处转移的显著预测指标。因此，凋亡或有丝分裂的预处理水平在分别分析时可能有助于预测NSCLC的SQ和AC/LC亚组的治疗结果，以及预测AC/LC的转移发生率。
