Sousa Vitor, Rodrigues Carolina, Silva Maria, Alarcão Ana Maria, Carvalho Lina
IAP-FMUC-Institute of Pathology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Pathology Institute, Coimbra University Hospital, Coimbra, Portugal.
IAP-FMUC-Institute of Pathology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Rev Port Pneumol (2006). 2015 May-Jun;21(3):113-25. doi: 10.1016/j.rppnen.2014.09.009. Epub 2015 Mar 11.
Pulmonary adenocarcinomas are still in the process of achieving morphological, immunohistochemical and genetic standardization. The ATS/ERS/IASLC proposed classification for lung adenocarcinomas supports the value of the identification of histological patterns, specifically in biopsies. Thirty pulmonary adenocarcinomas were subjected to immunohistochemical study (CK7, CK5, 6, 18, CK20, TTF1, CD56, HER2, EGFR and Ki-67), FISH and PCR followed by sequencing and fragment analysis for EGFR, HER2 and KRAS. Solid pattern showed lower TTF1 and higher Ki-67 expression. TTF1 expression was higher in non-mucinous lepidic and micropapillary patterns when compared to acinar and solid and acinar, solid and mucinous respectively. Higher Ki67 expression was present in lepidic and solid patterns compared to mucinous. EGFR membranous staining had increasing expression from non-mucinous lepidic/BA pattern to solid pattern and micropapillary until acinar pattern. EGFR mutations, mainly in exon 19, were more frequent in females, together with non-smoking status, while KRAS exon 2 mutations were statistically more frequent in males, especially in solid pattern. FISH EGFR copy was correlated gross, with mutations. HER2 copy number was raised in female tumours without mutations, in all cases. Although EGFR and KRAS mutations are generally considered mutually exclusive, in rare cases they can coexist as it happened in one of this series, and was represented in acinar pattern with rates of 42.9% and 17.9%, respectively. EGFR mutations were more frequent in lepidic/BA and acinar patterns. Some cases showed different EGFR mutations. The differences identified between the adenocarcinoma patterns reinforce the need to carefully identify the patterns present, with implications in diagnosis and in pathogenic understanding. EGFR and KRAS mutational status can be determined in biopsies representing bronchial pulmonary carcinomas because when a mutation is present it is generally present in all the histological patterns.
肺腺癌仍在实现形态学、免疫组织化学和基因标准化的过程中。美国胸科学会（ATS）/欧洲呼吸学会（ERS）/国际肺癌研究协会（IASLC）提出的肺腺癌分类支持识别组织学模式的价值，特别是在活检中。对30例肺腺癌进行了免疫组织化学研究（CK7、CK5、6、18、CK20、TTF1、CD56、HER2、EGFR和Ki-67）、荧光原位杂交（FISH）和聚合酶链反应（PCR），随后对EGFR、HER2和KRAS进行测序和片段分析。实性模式显示TTF1表达较低，Ki-67表达较高。与腺泡、实性以及腺泡、实性和黏液性模式相比，非黏液性鳞屑状和微乳头模式中的TTF1表达较高。与黏液性模式相比，鳞屑状和实性模式中Ki67表达较高。EGFR膜染色从非黏液性鳞屑状/原位腺癌（BA）模式到实性模式、微乳头模式直至腺泡模式，表达逐渐增加。EGFR突变主要发生在外显子19，在女性中更常见，且与不吸烟状态相关，而KRAS外显子2突变在男性中在统计学上更常见，尤其是在实性模式中。FISH检测的EGFR拷贝数与突变总体相关。在所有病例中，女性肿瘤中HER2拷贝数增加且无突变。尽管EGFR和KRAS突变通常被认为是相互排斥的，但在罕见情况下它们可以共存，本系列中的一例就是如此，在腺泡模式中发生率分别为42.9%和17.9%。EGFR突变在鳞屑状/原位腺癌和腺泡模式中更常见。一些病例显示出不同的EGFR突变。腺癌模式之间的差异强化了仔细识别所呈现模式的必要性，这对诊断和致病机制理解都有影响。在代表支气管肺癌的活检中可以确定EGFR和KRAS的突变状态，因为当存在突变时，它通常存在于所有组织学模式中。
