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首页> 外文期刊>British Journal of Cancer >KRAS, NRAS, BRAF mutation comparison of endoscopic and surgically removed primary CRC paired samples: is endoscopy biopsy material adequate for molecular evaluation?
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KRAS, NRAS, BRAF mutation comparison of endoscopic and surgically removed primary CRC paired samples: is endoscopy biopsy material adequate for molecular evaluation?

机译：内镜和手术切除的原发性CRC配对样品的 KRAS ， NRAS ， BRAF 突变比较：内窥镜活检材料是否足以进行分子评估？

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Background: An everyday clinical practice dilemma in the 20–30% of metastatic colorectal cancer (CRC) patients that have not been operated on their primary tumour, is, under which specific histopathology and molecular circumstances, an endoscopic biopsy could be considered adequate to provide a representative RAS/BRAF molecular status to guide treatment. Methods: A consecutive series of 193 paired biopsy and primary CRC tumour samples between August 2008 and 2010 available in the Department of Pathology archives, University Hospitals, KU Leuven were retrieved. For a pair to be included, in the endoscopic biopsy, 20% of invasive adenocarcinoma cells should be present and enough slides to yield an extracted DNA concentration of ?5?ng? μ l~(?1), and no <2?ng? μ l~(?1)should be available for cutting. Exons 2–4 KRAS/NRAS, BRAF, PIK3CA molecular evaluation was performed with RT–PCR and Sequenom. Results: From 165 deemed adequate by the pathologist pairs, 85 (51.5%) were concordantly mutated in at least one of the tested genes, 70 (42.5%) were wt and 10 (6%) were discordant, harbouring a mutation in the primary and not in the endoscopic biopsy. In the re-evaluation, when more slides were cut per discordant pair, mutational status changed in two of the six discordantly KRAS -mutated pairs. A strong strength of agreement for both runs was observed (Cohen's kappa, k =0.877, P <0.001 and k =0.901, P <0.001, respectively) between the surgically acquired and the endoscopic biopsy specimens' evaluation. Conclusions: Based on our results, an endoscopic biopsy could provide an accurate mutational profile and become a justified alternative to a surgically removed primary tumour specimen, as long as specific histopathology criteria are met.
机译：背景：在未进行原发肿瘤手术的转移性结直肠癌（CRC）患者中，有20–30％的日常临床实践困境是，在这种情况下，根据特定的组织病理学和分子情况，可以认为内镜活检足以提供具有代表性的RAS / BRAF分子状态来指导治疗。方法：检索2008年8月至2010年之间连续193次配对的活检和原发性CRC肿瘤样本，这些样本可从鲁汶大学医院病理学系档案中获得。对于内镜下活检中要包括的一对，应存在20％的浸润性腺癌细胞，并有足够的载玻片以产生提取的DNA浓度“ 5？ng”？ μl〜（？1），否<2？ng？ μl〜（？1）应该可以切割。外显子2-4 KRAS / NRAS，BRAF，PIK3CA分子评估是通过RT-PCR和Sequenom进行的。结果：从病理学家对认为合适的165个基因中，至少有一个测试基因中85个（51.5％）被一致地突变，其中70个（42.5％）被wt和10个（6％）不协调，在原发中具有突变而不是在内窥镜活检中。在重新评估中，当每对不一致的对切出更多的玻片时，在六个不一致的KRAS突变对中，有两个突变状态发生了变化。在手术获得的和内窥镜活检样本的评估之间，观察到两种试验的一致性很强（分别为Cohen's kappa，k = 0.877，P <0.001和k = 0.901，P <0.001）。结论：根据我们的结果，只要符合特定的组织病理学标准，内窥镜活检可以提供准确的突变特征，并成为手术切除的原发肿瘤标本的合理替代方案。

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