Confavreux Cyrille B, Girard Nicolas, Pialat Jean-Baptiste, Bringuier Pierre-Paul, Devouassoux-Shisheboran Mojgan, Rousseau Jean-Charles, Isaac Sylvie, Thivolet-Bejui Françoise, Clezardin Philippe, Brevet Marie
Inserm UMR1033-Université de Lyon , Lyon, France ; Rheumatology Department, Hôpital Edouard Herriot, Hospices Civils de Lyon , Lyon, France.
Respiratory Medicine, Thoracic Oncology Department, Hôpital Louis Pradel, Hospices Civils de Lyon , Lyon, France.
Bonekey Rep. 2014 Oct 1;3:580. doi: 10.1038/bonekey.2014.75. eCollection 2014.
Targeted therapies have improved patient survival in metastatic lung adenocarcinoma. Molecular diagnosis is a key element to identify oncogenic drivers predicting the efficacy of these agents. In stage IV patients, histopathological diagnosis is often performed on bone metastases biopsy, but routine procedure of decalcification may alter DNA quality for subsequent molecular tests. We set up a procedure to perform molecular analyses on bone metastasis and describe the results of mutational profiling. POUMOS-TEC is a prospective study conducted in stage IV lung adenocarcinomas. Bone metastasis specimens from surgery and CT-scan guided biopsies were sent fresh for immediate formalin-fixation. Decalcification was performed, only when necessary, using EDTA. Controls were processed with acid decalcification. DNA extraction was performed after laser microdissection. Mutational profiling of oncogenic drivers was conducted as recommended by the French National Cancer Institute. Diagnosis efficiency of the computed tomography (CT)-scan guided biopsy process was assessed. Among 177 collected bone metastases specimens, 49 came from lung adenocarcinomas. Specimens processed with no decalcification or EDTA (n=45) provided high-quality DNA. Molecular profiling was performed in 44/45 (98%) of cases. The results of the whole panel of oncogenic drivers (EGFR, KRAS, BRAF, PIK3CA, HER2 and ALK) were obtained in 41/45 (91%) of cases. A mutation was observed in 50% of cases including 32% of KRAS and 14% of epidermal growth factor receptor (EGFR) mutations. CT-scan biopsy efficiency rate was 96%. We demonstrated the feasibility to routinely conduct mutational profiling on bone metastases biopsies. We observed a higher rate of EGFR mutations (+42%) in comparison with the average rate of all stage IV lung adenocarcinomas. This procedure is a new step toward the goal of personalized medicine to treat lung cancers and other osteophilic tumors.
靶向治疗提高了转移性肺腺癌患者的生存率。分子诊断是识别预测这些药物疗效的致癌驱动因素的关键要素。在IV期患者中，组织病理学诊断通常在骨转移活检时进行，但常规脱钙程序可能会改变DNA质量，影响后续分子检测。我们建立了一种对骨转移进行分子分析的程序，并描述了突变谱分析的结果。POUMOS-TEC是一项针对IV期肺腺癌开展的前瞻性研究。手术获取的骨转移标本以及CT引导下活检获取的标本均新鲜送检，立即用福尔马林固定。仅在必要时使用乙二胺四乙酸（EDTA）进行脱钙。对照组采用酸脱钙处理。激光显微切割后进行DNA提取。按照法国国家癌症研究所的建议进行致癌驱动因素的突变谱分析。评估计算机断层扫描（CT）引导下活检过程的诊断效率。在收集的177份骨转移标本中，49份来自肺腺癌。未进行脱钙或采用EDTA处理的标本（n = 45）提供了高质量的DNA。44/45（98%）的病例进行了分子谱分析。41/45（91%）的病例获得了全部致癌驱动因素（表皮生长因子受体（EGFR）、 Kirsten大鼠肉瘤病毒癌基因同源物（KRAS）、B-Raf原癌基因丝氨酸/苏氨酸激酶（BRAF）、磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α（PIK3CA）、人表皮生长因子受体2（HER2）和间变性淋巴瘤激酶（ALK））的结果。50%的病例观察到突变，其中KRAS突变占32%，EGFR突变占14%。CT活检效率为96%。我们证明了对骨转移活检进行常规突变谱分析的可行性。与所有IV期肺腺癌的平均发生率相比，我们观察到EGFR突变率更高（+42%）。这一程序是朝着肺癌和其他亲骨性肿瘤个性化医疗目标迈出的新一步。
