Yip T T, Lau W H, Chan J K, Ngan R K, Poon Y F, Lung C W, Lo T Y, Ho J H
Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong.
Cancer. 1998 Dec 1;83(11):2284-92.
Nasopharyngeal carcinoma (NPC) is a prevalent malignant tumor among Southern Chinese. Previously, the authors described the prognostic significance of a serum antibody assay to a recombinant Epstein-Barr virus Bam HI-Z replication activator protein (ZEBRA) in NPC patients with long term follow-up. In this study, the authors further reported the use of DNA flow cytometry (DNA-FCM) as an additional technique for determining the prognosis of NPC patients in the same series.
One hundred and forty-three archival biopsies from 110 NPC patients were deparaffinized and subjected to DNA-FCM analysis. DNA ploidy state and various proliferative indices (PI) of the tumors were correlated with patient survival and frequency of recurrence.
Among the biopsies analyzed, 119 were histologically positive NPC and 24 were negative. Fifty-one tumor biopsies that fulfilled the guideline criteria of the DNA Cytometry Consensus Conference were correlated with the clinical manifestations of the patients. Among them, 43 tumors (84%) were DNA diploid and 8 (16%) were aneuploid. Two PI, S-phase fraction (SPF) and proliferation fraction (PF), appear to be potentially useful prognostic indicators. For example, PF in patients who developed locoregional recurrence (15.1%) and distant recurrence (16.4%) after radiation therapy both were significantly higher than PF in patients who were in complete remission (8.2%) (P = 0.0005 and P = 0.004, respectively). Significant differences in SPF between patients with distant recurrence (10.6%) and those in remission (5.7%) also was found (P = 0.005). Using Kaplan-Meier analysis, patients with high PF, high SPF, and aneuploid tumors had significantly poorer 12-year survival rates (35%, 26%, and 28%, respectively) than those patients with low PF, low SPF, and diploid tumors (77%, 67%, and 59%, respectively) (P < 0.0009, P < 0.004, and P < 0.01, respectively).
Determination of tumor PI and DNA ploidy state by DNA-FCM at diagnosis of NPC can be potentially useful in selecting a poor prognostic subgroup of NPC patients. These parameters may enable oncologists to plan for more stringent treatment strategies such as hyperfractionated and accelerated radiation therapy or concomitant chemoradiotherapy for these patients.
鼻咽癌(NPC)是中国南方常见的恶性肿瘤。此前,作者描述了重组EB病毒Bam HI-Z复制激活蛋白(ZEBRA)血清抗体检测在长期随访的NPC患者中的预后意义。在本研究中,作者进一步报告了使用DNA流式细胞术(DNA-FCM)作为同一队列中确定NPC患者预后的另一项技术。
对110例NPC患者的143份存档活检标本进行脱石蜡处理,并进行DNA-FCM分析。肿瘤的DNA倍体状态和各种增殖指数(PI)与患者生存率和复发频率相关。
在分析的活检标本中,119份组织学检查为NPC阳性,24份为阴性。51份符合DNA细胞术共识会议指南标准的肿瘤活检标本与患者的临床表现相关。其中,43个肿瘤(84%)为DNA二倍体,8个(16%)为非整倍体。两个PI,即S期分数(SPF)和增殖分数(PF),似乎是潜在有用的预后指标。例如,放疗后出现局部区域复发(15.1%)和远处复发(16.4%)的患者的PF均显著高于完全缓解患者的PF(8.2%)(分别为P = 0.0005和P = 0.004)。远处复发患者(10.6%)与缓解患者(5.7%)之间的SPF也存在显著差异(P = 0.005)。使用Kaplan-Meier分析,PF高、SPF高和肿瘤为非整倍体的患者12年生存率(分别为35%、26%和28%)明显低于PF低、SPF低和肿瘤为二倍体的患者(分别为77%、67%和59%)(分别为P < 0.0009、P < 0.004和P < 0.01)。
在NPC诊断时通过DNA-FCM测定肿瘤PI和DNA倍体状态可能有助于选择预后不良的NPC患者亚组。这些参数可能使肿瘤学家能够为这些患者制定更严格的治疗策略,如超分割和加速放疗或同步放化疗。