Chudacek Josef, Bohanes Tomas, Klein Jiri, Benedikova Andrea, Srovnal Josef, Szkorupa Marek, Skalicky Pavel, Skarda Jozef, Hajduch Marian, Neoral Cestmir
Department of Surgery I, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic.
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2014 Jun;158(2):189-93. doi: 10.5507/bp.2013.019. Epub 2013 Apr 2.
Even after successful radical treatment of lung cancer, patients in stages I and II of the TNM system very frequently suffer recurrence, which end lethally. Detection of subclinical residual disease after surgery is thus one of the most important emerging diagnostic methods. Minimal residual disease (MRD) is defined as the presence of isolated tumor cells or circulating cells in a patient after curative primary tumor removal and at the same time, no clinical signs of cancer. Conventional methods cannot detect minimal residual disease and hence there is a need for detection using new molecular biological methods.
We searched the PubMed database for original and review articles on minimal residual disease in lung cancer. Search words were "lung cancer", "minimal residual disease" and "detection of minimal residual disease". The publications we found were compared with the results of our own studies on the detection of minimal residual disease in lung cancer and the personal experiences are described. Examination of blood samples from 98 healthy volunteers and bone marrow from 12 patients with non inflammatory and non tumour illness, were used to determine cut-off values for specific markers in the compartments. Subsequently, expression of selected markers in tumor tissue was analysed in a pilot sample of 50 patients with lung cancer and the presence of MRD was measured as expression of values of the tested markers correlated with clinico-pathological characteristics.
Recent studies on other malignancies apart from lung cancer have shown the importance of MRD detection in the determination of disease progression and prognosis. The methods of MRD diagnostics are based on detection of specific tumor markers. Of these, the most specific for lung cancer, appears to be the LunX protein. The best method for determining MRD is probably RT-PCR. Further studies should expand knowledge in this area: to refine understanding of the importance of tumor markers for prognosis, as well as to confirm the significance of these findings in clinical practice.
即使肺癌经过成功的根治性治疗，TNM系统I期和II期的患者仍经常复发，最终导致死亡。因此，术后亚临床残留病灶的检测是最重要的新兴诊断方法之一。微小残留病（MRD）定义为患者在原发性肿瘤根治性切除后存在孤立的肿瘤细胞或循环细胞，且同时无癌症的临床体征。传统方法无法检测微小残留病，因此需要使用新的分子生物学方法进行检测。
我们在PubMed数据库中搜索了有关肺癌微小残留病的原始文章和综述文章。搜索词为“肺癌”“微小残留病”和“微小残留病的检测”。将我们找到的出版物与我们自己关于肺癌微小残留病检测的研究结果进行比较，并描述个人经验。对98名健康志愿者的血样和12名非炎性非肿瘤疾病患者的骨髓进行检测，以确定各区域特定标志物的临界值。随后，在50例肺癌患者的试验样本中分析肿瘤组织中所选标志物的表达情况，并将检测标志物的值与临床病理特征相关联来测量MRD的存在情况。
除肺癌外，最近对其他恶性肿瘤的研究表明，MRD检测在疾病进展和预后判定中具有重要意义。MRD诊断方法基于特定肿瘤标志物的检测。其中，对肺癌最具特异性的似乎是LunX蛋白。确定MRD的最佳方法可能是逆转录聚合酶链反应（RT-PCR）。进一步的研究应扩展该领域的知识：深化对肿瘤标志物预后重要性的理解，并在临床实践中证实这些发现的意义。
