病理分期为N1的非小细胞肺癌的预后生物标志物研究

Prognostic biomarker study in pathologically staged N1 non-small cell lung cancer.

作者信息

Komaki R, Milas L, Ro J Y, Fujii T, Perkins P, Allen P, Sikes C R, Mountain C F, Ordonez N G

机构信息

Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.

出版信息

Int J Radiat Oncol Biol Phys. 1998 Mar 1;40(4):787-96. doi: 10.1016/s0360-3016(97)00898-5.

DOI:10.1016/s0360-3016(97)00898-5

PMID:9531362

Abstract

PURPOSE

The prognostic influence of 6 biomarkers correlated to histologic subtypes of non-small cell lung cancer (NSCLC) on loco-regional control, overall survival, disease-free survival (DFS), and distant disease control (DDC) rates, all measured at 5 years, were examined.

MATERIALS & METHODS: Cell blocks from the primary tumors of 137 patients with pathologically staged N1 NSCLC at MDACC were analyzed by 6-biomarker status correlated to histological subtypes and their outcomes.

RESULTS

The ranges of biomarker values were as follows: apoptotic index, 0.2-2.8%; mitotic index, 0-1.8%; the proportion of cells in S+G2M, 3-36%; p53 status, 0-100%; Ki-67, 0-9.3%; DNA index, 1.0-2.74. Subtypes of 137 cases from the postoperative pathology specimen showed that 74 patients had squamous carcinoma and 63 patients had adenocarcinoma. Mean and median lengths of follow-up were 4.21 years and 2.43 years, respectively. Patients with squamous cell carcinoma (SCC) had a better 5-year survival (p = 0.006), DFS (p = 0.002), and distant metastasis control (p = 0.002) than patients with adenocarcinoma (AC). Among patients with AC, the DNA index was a significant predictor of 5-year DFS (p = 0.02), DDC rate (p = 0.04), and local-regional control (p < 0.05). Higher apoptosis (p = 0.03) and mitosis indices (p = 0.03) were also univariate predictors of increased distant disease among patients with AC. Multivariate analysis of patients with AC revealed that the DNA index and Ki-67 were the only significant independent predictors of distant metastasis (p < 0.04 and p < 0.02, respectively) and DFS (p < 0.04 for both). Among patients with SCC, univariate analysis showed that S+G2M proportion (p < 0.05) and Ki-67 levels (p < 0.02) were significant predictors for local-regional control; for SC, multivariate analysis showed that only mitosis was a significant predictor in this case for overall survival (p < 0.04).

CONCLUSION

Spontaneous apoptotic index and Ki-67 were significantly higher in SC than in AC. Patients with SC had less distant metastasis better DFS and overall survival than those with AC. Multivariate analysis revealed that DNA index and Ki-67 status were significant predictors for DDC and DFS in patients with AC, but only mitotic index was a significant predictor of overall survival for patients with SCC.

摘要

目的

研究6种与非小细胞肺癌（NSCLC）组织学亚型相关的生物标志物对局部区域控制、总生存期、无病生存期（DFS）和远处疾病控制（DDC）率的预后影响，所有指标均在5年时进行测量。

材料与方法

对MDACC的137例病理分期为N1期NSCLC患者的原发肿瘤细胞块进行分析，根据与组织学亚型相关的6种生物标志物状态及其结果进行分析。

结果

生物标志物值的范围如下：凋亡指数，0.2 - 2.8%；有丝分裂指数，0 - 1.8%；S + G2M期细胞比例，3 - 36%；p53状态，0 - 100%；Ki - 67，0 - 9.3%；DNA指数，1.0 - 2.74。术后病理标本的137例病例的亚型显示，74例为鳞状细胞癌，63例为腺癌。平均随访时间和中位随访时间分别为4.21年和2.43年。鳞状细胞癌（SCC）患者的5年生存率（p = 0.006）、DFS（p = 0.002）和远处转移控制率（p = 0.002）均优于腺癌（AC）患者。在AC患者中，DNA指数是5年DFS（p = 0.02）、DDC率（p = 0.04）和局部区域控制（p < 0.05）的显著预测指标。较高的凋亡（p = 0.03）和有丝分裂指数（p = 0.03）也是AC患者远处疾病增加的单因素预测指标。对AC患者的多因素分析显示，DNA指数和Ki - 67是远处转移（分别为p < 0.04和p < 0.02）和DFS（两者均为p < 0.04）的唯一显著独立预测指标。在SCC患者中，单因素分析显示S + G2M期比例（p < 0.05）和Ki - 67水平（p < 0.02）是局部区域控制的显著预测指标；对于SCC，多因素分析显示在这种情况下只有有丝分裂是总生存期的显著预测指标（p < 0.04）。