Yu DA-Ping, Dong Yu-Jie, Zhang Hai-Qing, Wang Jing-Hui, Qu Yang, Zhou Li-Juan, Su Dan, Zhang Li-Li, Zhao Dan, Cai Yi-Ran
Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, Beijing 101149, P.R. China.
Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing 101149, P.R. China.
Biomed Rep. 2014 Jul;2(4):481-489. doi: 10.3892/br.2014.261. Epub 2014 Mar 20.
Non-small-cell lung cancer (NSCLC) is the most common cause of cancer-related mortality. Adenocarcinoma (AC) is the predominant histological type of NSCLC; however, AC consists of several subtypes. It has not yet been determined whether there is a correlation of CRKL and AXL expression with epidermal growth factor receptor () and anaplastic lymphoma kinase () gene status in lung AC. We assayed exons 18 through 21 of the gene by direct sequencing; rearrangement and the expression of CRKL and AXL were detected by immunostaining. A total of 212 cases of AC were included in this study, diagnosed using the novel classification system established by the International Association for the Study of Lung Cancer, the American Thoracic Society and the European Respiratory Society in 2011, including 69 acinar ACs, 17 lepidic predominant ACs (LPAs), 63 papillary, 14 mucinous, 17 micropapillary and 32 solid ACs. Of the 212 cases, 101 harbored mutations. The most common subtypes carrying delK745-S753 were papillary and acinar ACs. rearrangement was found in 23 cases (11%) of lung ACs. Acinar and solid ACs were the most frequent subtypes with aberrance, particularly in acinar ACs with cribriform structure (4/5 cases, 80%). The expression of CRKL was significantly different among the AC subtypes (P=0.01), with the highest and lowest expression levels of CRKL protein in papillary ACs and LPAs, respectively (P<0.05). AXL expression was also significantly different among the AC subtypes (P=0.002) and was correlated with lymph node infiltration in acinar ACs. ACs with mutations exhibited high levels of AXL protein expression compared to those without mutations (P<0.001). Acinar AC with cribriform structure is a distinct subtype that frequently harbors rearrangement. The activation of may be one of the factors contributing to the invasion of acinar and micropapillary ACs.
非小细胞肺癌（NSCLC）是癌症相关死亡的最常见原因。腺癌（AC）是NSCLC的主要组织学类型；然而，AC由几种亚型组成。目前尚未确定CRKL和AXL表达与肺AC中表皮生长因子受体（）和间变性淋巴瘤激酶（）基因状态是否存在相关性。我们通过直接测序检测了该基因的18至21外显子；通过免疫染色检测了CRKL和AXL的重排及表达。本研究共纳入212例AC病例，采用国际肺癌研究协会、美国胸科学会和欧洲呼吸学会于2011年建立的新分类系统进行诊断，包括69例腺泡状AC、17例鳞屑为主型AC（LPA）、63例乳头状、14例黏液性、17例微乳头状和32例实性AC。在212例病例中，101例存在 突变。携带delK745 - S753的最常见亚型是乳头状和腺泡状AC。在23例（11%）肺AC病例中发现了 重排。腺泡状和实性AC是 异常最常见的亚型，尤其是在具有筛状结构的腺泡状AC中（4/5例，80%）。CRKL的表达在AC亚型之间存在显著差异（P = 0.01），CRKL蛋白表达水平在乳头状AC中最高，在LPA中最低（P < 0.05）。AXL表达在AC亚型之间也存在显著差异（P = 0.002），并且与腺泡状AC中的淋巴结浸润相关。与无突变的AC相比，有 突变的AC表现出高水平的AXL蛋白表达（P < 0.001）。具有筛状结构的腺泡状AC是一种独特的亚型，经常存在 重排。 的激活可能是导致腺泡状和微乳头状AC侵袭的因素之一。
