de Melo Andreia Cristina, Karen de Sá Vanessa, Sternberg Cinthya, Olivieri Eloisa Ribeiro, Werneck da Cunha Isabela, Fabro Alexandre Todorovic, Carraro Dirce Maria, de Barros e Silva Milton José, Pimenta Inada Haynna Kimie, de Mello Evandro Sobrosa, Soares Fernando Augusto, Takagaki Tereza, Ferreira Carlos Gil, Capelozzi Vera Luiza
Department of Pathology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Oncology. 2015;89(3):175-86. doi: 10.1159/000376552. Epub 2015 Apr 1.
To show additional prognostic information about the mutational profile and new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification of adenocarcinoma (ADC) in patients without epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor treatments.
In human lung ADC patients (n = 125), including 24 lepidic, 67 acinar, 23 papillary, and 11 solid predominant subtypes, EGFR and KRAS were sequenced, and anaplastic lymphoma kinase (ALK) rearrangements were screened using fluorescence in situ hybridization (FISH).
EGFR was mutated in 21.6% of patients with 19.57% showing a mean expression. The most frequent EGFR mutation was a deletion in exon 19, followed by an L858R amino acid substitution in exon 21. KRAS was mutated in 26.4% of patients with 50% displaying mean expression. ALK rearrangement was detected in 6 patients (4.8%). Predominant acinar ADC was strongly associated with EGFR and KRAS mutation. Clinical stage, lymph node metastases, and EGFR mutation in exon 18 showed a significant difference in disease-free and overall survival, but only a trend significance for EGFR and KRAS mutations. Multivariate analysis revealed that men aged >71 years, with a history of smoking (<72 packs/year), clinical stage I/II, and acinar histologic subtype presented better survival than women aged ≤ 71 years, with a history of smoking (>72 packs/year), and having a predominant solid ADC and EGFR mutation in exon 18.
These results indicate that the mutational profile and new IASLC/ATS/ERS classification provide additional prognostic information about lung ADC.
展示在未接受表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂治疗的患者中，关于腺癌（ADC）突变谱及新的国际肺癌研究协会/美国胸科学会/欧洲呼吸学会（IASLC/ATS/ERS）分类的额外预后信息。
在125例人肺ADC患者中，包括24例鳞屑状、67例腺泡状、23例乳头状和11例实性为主型亚型，对EGFR和KRAS进行测序，并使用荧光原位杂交（FISH）筛选间变性淋巴瘤激酶（ALK）重排。
21.6%的患者EGFR发生突变，其中19.57%表现为平均表达。最常见的EGFR突变是外显子19缺失，其次是外显子21中的L858R氨基酸取代。26.4%的患者KRAS发生突变，其中50%表现为平均表达。6例患者（4.8%）检测到ALK重排。主要的腺泡状ADC与EGFR和KRAS突变密切相关。临床分期、淋巴结转移和外显子18中的EGFR突变在无病生存期和总生存期方面存在显著差异，但EGFR和KRAS突变仅具有趋势性意义。多因素分析显示，年龄>71岁、有吸烟史（<72包/年）、临床分期I/II且组织学亚型为腺泡状的男性患者，比年龄≤71岁、有吸烟史（>72包/年）、主要为实性ADC且外显子18有EGFR突变的女性患者生存情况更好。
这些结果表明，突变谱及新的IASLC/ATS/ERS分类为肺ADC提供了额外的预后信息。
