Ohali A, Avigad S, Cohen I J, Meller I, Kollender Y, Issakov J, Gelernter I, Goshen Y, Yaniv I, Zaizov R
Department of Molecular Oncology, Felenstein Medical Research Center, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
J Clin Oncol. 2003 Oct 15;21(20):3836-43. doi: 10.1200/JCO.2003.05.059.
Telomerase is considered a molecular marker for malignancy. The aim of this study was to determine telomerase activity (TA) as a prognostic factor at diagnosis and as a marker for minimal residual disease during therapy and follow-up in nonmetastatic Ewing family of tumors (EFT).
Primary tumor specimens and 97 peripheral blood (PBL) samples from 31 EFT patients were analyzed for TA by the Telomeric Repeat Amplification Protocol (TRAP assay). The telomerase catalytic subunit (human telomerase reverse transcriptase [hTERT]) gene expression was evaluated by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and telomere length was determined by Southern blotting. The presence of the EFT chimeric transcripts was analyzed by RT-PCR. Correlations with progression-free survival were evaluated.
At diagnosis, TA in primary tumors did not correlate with outcome. During therapy and follow-up, highly significant correlation was observed between high TA in PBL samples and adverse prognosis (P <.0001). None of the patients harboring low TA progressed, with a long follow-up (median, 60 months) and a progression-free survival (PFS) of 100%. In nine patients, high TA actually could predict relapse, long before overt clinical relapse. The group of patients with high TA and positive RT-PCR had the most adverse outcome; PFS of 20% (P =.0025). TA was found to be a better prognostic factor than RT-PCR and histopathologic response at surgery.
The results suggest that TA is a significant prognostic variable, superior to the established clinical prognostic parameters during therapy and tumor surveillance. It could be used in combination with RT-PCR for a new risk classification.
端粒酶被认为是恶性肿瘤的分子标志物。本研究的目的是确定端粒酶活性（TA）作为非转移性尤因家族性肿瘤（EFT）诊断时的预后因素以及治疗和随访期间微小残留病的标志物。
采用端粒重复序列扩增法（TRAP 分析）对 31 例 EFT 患者的原发性肿瘤标本和 97 份外周血（PBL）样本进行 TA 分析。通过定量逆转录聚合酶链反应（RT-PCR）评估端粒酶催化亚基（人端粒酶逆转录酶[hTERT]）基因表达，并通过 Southern 印迹法测定端粒长度。通过 RT-PCR 分析 EFT 嵌合转录本的存在情况。评估与无进展生存期的相关性。
诊断时，原发性肿瘤中的 TA 与预后无关。在治疗和随访期间，观察到 PBL 样本中高 TA 与不良预后之间存在高度显著相关性（P <.0001）。TA 低的患者无一进展，随访时间长（中位时间，60 个月），无进展生存期（PFS）为 100%。在 9 例患者中，高 TA 实际上可在明显临床复发前很久预测复发。TA 高且 RT-PCR 阳性的患者组预后最差；PFS 为 20%（P =.0025）。发现 TA 是比 RT-PCR 和手术时的组织病理学反应更好的预后因素。
结果表明，TA 是一个重要的预后变量，在治疗和肿瘤监测期间优于既定的临床预后参数。它可与 RT-PCR 联合用于新的风险分类。
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