Comparison of oncogene mutation detection and telomerase activity for the molecular staging of non-small cell lung cancer.
Comparison of oncogene mutation detection and telomerase activity for the molecular staging of non-small cell lung cancer.
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发表时间：
1997-07
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通讯作者：
S. Ahrendt;Stephen C. Yang;Li Wu;W. Westra;Jin Jen;J. Califano;D. Sidransky
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作者：
S. Ahrendt;Stephen C. Yang;Li Wu;W. Westra;Jin Jen;J. Califano;D. Sidransky
新型癌基因突变检测技术已经证明，标准组织病理学检查可能无法检测出具有临床意义的转移性癌细胞。最近，在大多数永生细胞系和人类肿瘤中检测到端粒酶活性，这可能提供一种新的诊断标记物。我们将标准组织病理学检查与端粒重复扩增方案测定以及 p53 斑块杂交或 K-ras 突变连接测定在 12 例可手术切除的非小细胞肺癌患者的淋巴结中进行比较。在 10 个可评估肿瘤中的 10 个 (100%) 中检测到端粒酶活性。 9 个组织病理学阳性淋巴结中的 8 个（89%）端粒酶阳性，48 个组织病理学阴性淋巴结中的 26 个（54%）端粒酶阳性。相比之下，寡核苷酸噬斑杂交在所有 3 个组织病理学阳性节点和 27 个组织病理学阴性节点中的 3 个中检测到转移。同样，K-ras 突变连接试验在所有 6 个组织病理学阳性淋巴结中检测到转移，在 21 个组织病理学阴性淋巴结中检测到 1 个转移。因此，端粒酶测定的大多数“阳性”节点并不含有与原发肿瘤具有相同遗传改变的隐匿性肿瘤细胞。与端粒重复扩增方案检测相关的高假阳性率限制了其在非小细胞肺癌患者淋巴结分期中的作用。
Novel oncogene mutation detection techniques have demonstrated that standard histopathological examination may fail to detect clinically significant metastatic cancer cells. Recently, telomerase activity has been detected in most immortal cell lines and human tumors, potentially providing a novel diagnostic marker. We compared standard histopathological examination with the telomeric repeat amplification protocol assay and either a p53 plaque hybridization or a K-ras mutation ligation assay in the lymph nodes of 12 patents with surgically resectable non-small cell lung cancer. Telomerase activity was detected in 10 of 10 (100%) evaluable tumors. Eight of 9 (89%) histopathologically positive lymph nodes were telomerase positive, and 26 of 48 (54%) histopathologically negative lymph nodes were telomerase positive. In comparison, oligonucleotide plaque hybridization detected metastases in all 3 histopathologically positive nodes and in 3 of 27 histopathologically negative nodes. Similarly, the K-ras mutation ligation assay detected metastases in all 6 histopathologically positive lymph nodes examined and in 1 of 21 histopathologically negative lymph nodes. Thus, most of the "positive" nodes by telomerase assay did not harbor occult neoplastic cells that shared the same genetic alteration as the primary tumor. The high rate of false positives associated with the telomeric repeat amplification protocol assay limits its role in staging lymph nodes in patients with non-small cell lung cancer.