Frick Glen S, Pitari Giovanni M, Weinberg David S, Hyslop Terry, Schulz Stephanie, Waldman Scott A
Respiratory & Inflammation Centre of Excellence for Drug Discovery, Discovery Medicine, GlaxoSmithKline, PA, USA.
Expert Rev Mol Diagn. 2005 Sep;5(5):701-13. doi: 10.1586/14737159.5.5.701.
Staging patients with colorectal cancer defines their prognosis and therapeutic management. Unfortunately, histopathology, the current standard for staging, is relatively insensitive for detecting occult micrometastases and a significant fraction of patients are understaged and, consequently, undertreated. Similarly, current approaches to postoperative surveillance of patients with colorectal cancer detect disease recurrence at a point when interventions have little impact on survival. The detection of rare cells in tissue, for accurately staging patients, and in blood, for detecting disease recurrence, could be facilitated by employing sensitive and specific markers of disease. Guanylyl cyclase C (GCC), the receptor for the diarrheagenic bacterial heat-stable enterotoxin, is expressed selectively by cells derived from intestinal mucosa, including normal intestinal cells and colorectal tumor cells, but not by extragastrointestinal tissues and tumors. The nearly uniform expression of relatively high levels by metastatic colorectal tumors suggests that GCC may be a sensitive and specific molecular marker for metastatic colorectal cancer cells. Employing GCC reverse transcriptase PCR, occult colorectal cancer micrometastases were detected in lymph nodes that escaped detection by histopathology. Moreover, marker expression correlated with the risk of disease recurrence. Similarly, GCC reverse transcriptase PCR revealed the presence of tumor cells in blood of all patients examined with metastatic colorectal cancer and, in some studies, was associated with an increased risk of disease recurrence and mortality. These observations suggest that GCC reverse transcriptase PCR is a sensitive and specific technique for identifying tumor cells in extraintestinal sites and may be useful for staging and postoperative surveillance of patients with colorectal cancer.
对结直肠癌患者进行分期可明确其预后并指导治疗管理。遗憾的是，作为当前分期标准的组织病理学在检测隐匿性微转移方面相对不敏感，相当一部分患者分期过低，因此治疗不足。同样，目前结直肠癌患者术后监测方法在疾病复发时才能检测到，而此时干预对生存率影响甚微。通过使用敏感且特异的疾病标志物，有助于在组织中准确对患者进行分期以检测罕见细胞，以及在血液中检测疾病复发。鸟苷酸环化酶C（GCC）是致腹泻性细菌热稳定肠毒素的受体，由包括正常肠细胞和结直肠肿瘤细胞在内的肠黏膜来源细胞选择性表达，但胃肠道外组织和肿瘤不表达。转移性结直肠癌中相对高水平的几乎一致表达表明，GCC可能是转移性结直肠癌细胞的敏感且特异的分子标志物。采用GCC逆转录聚合酶链反应（PCR），在组织病理学未能检测到的淋巴结中发现了隐匿性结直肠癌微转移。此外，标志物表达与疾病复发风险相关。同样，GCC逆转录PCR揭示了所有接受检查的转移性结直肠癌患者血液中存在肿瘤细胞，并且在一些研究中，与疾病复发和死亡风险增加相关。这些观察结果表明，GCC逆转录PCR是一种用于识别肠外部位肿瘤细胞的敏感且特异的技术，可能有助于结直肠癌患者的分期和术后监测。
