Department of Pulmonology, Albert Schweitzer Hospital, Dordrecht, The Netherlands.
Department of Pulmonology, VU University Medical Center, Amsterdam, The Netherlands.
Lung Cancer. 2015 Jul;89(1):19-26. doi: 10.1016/j.lungcan.2015.04.005. Epub 2015 Apr 20.
Adenocarcinoma (ADC) of the lung may harbor EGFR- or KRAS-mutations, which are relevant for treatment decisions. There is no consensus on the percentages of EGFR- and KRAS-mutations that are allowed to be missed by a diagnostic algorithm, although a percentage of less than 1% for EGFR-mutations has been suggested. The current guidelines do not advise to perform EGFR-mutation analysis in unequivocal squamous cell carcinoma (SqCC). For KRAS-mutations no threshold for missing cases is suggested yet. To improve segregation between ADC and SqCC in small samples, the classification of lung cancer was updated in 2011, adding immunohistochemistry (IHC) for p63 and TTF-1 to the diagnostic algorithm. In this study we examined how many cases with an EGFR- or KRAS-mutation in our database would have been missed, if the current guideline for selecting cases for mutation analysis would have been applied.
From an institutional lung cancer database of specimens analyzed for EGFR- and KRAS-mutations (n=816), cases harboring a mutation without being treated prior with an EGFR-TKI were selected (n=336). Corresponding original histological diagnoses and IHC for TTF-1, p63 and PAS-D were collected. Cases with SqCC on HE or with an IHC pattern favoring SqCC were reassessed according to the criteria of the 2011-classification.
From the 336 cases 70% had a KRAS-mutation and 30% an EGFR-mutation. The number of cases with SqCC on HE and/or an IHC-profile favoring SqCC was 12. After the reassessment six specimens (1.8%) would not have been tested for EGFR-/KRAS-mutations, if the current diagnostic algorithm had been used: 2.0% of EGFR-mutations and 1.7% KRAS-mutations. All six cases were NSCLC with an IHC-profile favoring SqCC.
Most NSCLC-cases with EGFR- and KRAS-mutations are selected by the current diagnostic algorithm. As a small but relevant fraction is missed, there is room for improvement.
肺腺癌（ADC）可能存在 EGFR 或 KRAS 突变，这与治疗决策相关。尽管已经提出 EGFR 突变允许漏诊的百分比应小于 1%，但对于诊断算法允许漏诊的 EGFR 和 KRAS 突变的百分比，尚无共识。目前的指南不建议在明确的鳞状细胞癌（SqCC）中进行 EGFR 突变分析。对于 KRAS 突变，尚未建议缺失病例的阈值。为了提高小样本中 ADC 和 SqCC 的分离度，2011 年更新了肺癌分类，在诊断算法中增加了 p63 和 TTF-1 的免疫组织化学（IHC）。在这项研究中，我们检查了如果应用当前的选择突变分析的指南，我们的数据库中会有多少 EGFR 或 KRAS 突变病例被遗漏。
从进行 EGFR 和 KRAS 突变分析的机构肺癌数据库中（n=816），选择了未进行 EGFR-TKI 治疗前携带突变的病例（n=336）。收集了相应的原始组织学诊断和 TTF-1、p63 和 PAS-D 的 IHC。根据 2011 年分类的标准，对 HE 上为 SqCC 或 IHC 模式倾向 SqCC 的病例进行重新评估。
在 336 例中，70%的病例有 KRAS 突变，30%的病例有 EGFR 突变。在 HE 上为 SqCC 和/或 IHC 模式倾向 SqCC 的病例数为 12 例。在重新评估后，如果使用当前的诊断算法，有 6 个标本（1.8%）将不会进行 EGFR-/KRAS 突变检测：2.0%的 EGFR 突变和 1.7%的 KRAS 突变。所有 6 个病例均为 NSCLC，IHC 模式倾向于 SqCC。
大多数 EGFR 和 KRAS 突变的 NSCLC 病例是通过当前的诊断算法选择的。由于有一小部分被遗漏，因此还有改进的空间。
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