融合基因阳性肺腺癌的病理组织学特征及与砂粒体的相关性研究

发布时间：2018-01-02 23:02

本文关键词：融合基因阳性肺腺癌的病理组织学特征及与砂粒体的相关性研究　出处：《中国癌症杂志》2016年08期 　论文类型：期刊论文

【摘要】：背景与目的:间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)、c-ros原癌基因1酪氨酸激酶(c-ros oncogene 1 receptor tyrosine kinase,ROS1)和RET融合基因被陆续证实为肺腺癌的驱动基因突变,并可在靶向治疗中获益。该研究旨在阐述融合基因阳性肺腺癌病理组织学特征,并探讨砂粒体与融合基因阳性肺腺癌的相关性。方法:收集复旦大学附属肿瘤医院原发肺腺癌患者手术切除新鲜标本和石蜡固定标本,检测肺腺癌标本中表皮生长因子受体(epidermal growth factor receptor,EGFR)、鼠类肉瘤病毒癌基因(Kirsten rat sarcoma viral oncogene,K-ras)、ALK、RET和ROS1基因突变状态。选取融合基因阳性肺腺癌病例44例(9例ROS1阳性,20例K-ras阳性,15例RET阳性)和融合基因阴性肺腺癌111例(20例EGFR突变,20例K-ras突变,71例未检测出基因突变)用于本项研究。根据2015年世界卫生组织(World Health Organization,WHO)肺腺癌新分类评估融合基因组与无融合基因组的病理组织学形态特征,并观察肺腺癌组织中砂粒体的数量及其分布的特征,并探讨砂粒体与融合基因阳性肺腺癌的相关性。结果:融合基因组中主要组织学亚型为腺泡状亚型(19/44,43.2%)和实体亚型(13/44,29.5%),无融合基因组主要组织学亚型为腺泡状亚型(50/111,45.0%)。实体亚型更多见于融合基因组,但两组间主要组织学亚型差异无统计学意义(P=0.060)。含印戒细胞成分、微乳头结构、黏液筛状结构及细胞外黏液分泌在融合基因组中阳性率均显著高于无融合基因组(P=0.000,P=0.044,P=0.000,P=0.010)。砂粒体在融合基因组阳性率显著高于无融合基因组(P=0.000),并且砂粒体与微乳头及黏液筛状结构具有显著相关性(P=0.000)。结论:实体亚型及腺泡状亚型常见于融合基因阳性肺腺癌。砂粒体、微乳头、细胞外黏液分泌、黏液筛状结构及含印戒细胞成分等特征性组织学形态与融合基因阳性肺腺癌密切相关,并且砂粒体与微乳头结构和(或)黏液筛状结构往往同时存在。通过对肺腺癌的特征性形态学观察对肺腺癌基因检测的优先性筛选具有指导意义。
[Abstract]:Background & objective: anaplastic lymphoma kinases (ALK) in anaplastic lymphoma. C-ros proto-oncogene 1 tyrosine kinase c-ros oncogene 1 receptor tyrosine kinase. ROS1) and RET fusion genes have been confirmed as driving gene mutations in lung adenocarcinoma, which can benefit from targeted therapy. The aim of this study was to elucidate the histopathological features of lung adenocarcinoma with positive fusion gene. Methods: fresh and paraffin fixed specimens were collected from primary lung adenocarcinoma patients in Fudan University affiliated Cancer Hospital. Epidermal growth factor receptor (EGFR) was detected in lung adenocarcinoma. Kirsten rat sarcoma viral oncogene of rodent sarcomavirus (ROV), K-rascogene, is ALK. Mutation status of RET and ROS1 genes. 44 cases of lung adenocarcinoma with fusion gene positive were selected. 9 cases were ROS1 positive and 20 cases were K-ras positive. There were 15 cases of RET positive) and 20 cases of EGFR mutation in 20 cases of lung adenocarcinoma with negative fusion gene. There were 20 cases of K-ras mutation. 71 cases of undetected gene mutations) were used in this study. According to the World Health Organization (WHO) World Health Organization in 2015. The new classification of lung adenocarcinoma was used to evaluate the histopathologic features of fusion genome and non-fusion genome, and to observe the quantity and distribution of sand particles in lung adenocarcinoma. Results: the main histological subtypes in the fusion genome were acinar subtype 19 / 44n43.2g) and solid subtype 13 / 44. 29.5 the main histological subtypes of the non-fused genome were acinar subtype 50 / 111 and 45.0%, and the entity subtype was more common in the fused genome. However, there was no significant difference in the main histological subtypes between the two groups. The positive rate of mucose-sieve structure and extracellular mucus secretion in the fusion genome was significantly higher than that in the non-fused genome (P = 0.000, P = 0.044, P = 0.000). The positive rate of sand particles in the fusion genome was significantly higher than that in the non-fused genome (P = 0.000). And there is a significant correlation between sand and micronipple and mucoid sieve structure. Conclusion: solid subtype and acinar subtype are common in fusion gene positive lung adenocarcinoma, sand particle, micropapilla. The characteristic histological morphology of extracellular mucus secretion, mucosieve structure and cell components containing signet ring is closely related to the fusion gene positive lung adenocarcinoma. Sand grains and micronipple structures and / or mucoid sieve structures often exist at the same time. The characteristic morphological observation of lung adenocarcinoma has guiding significance for the priority screening of lung adenocarcinoma gene detection.
【作者单位】：复旦大学附属肿瘤医院病理科复旦大学上海医学院肿瘤学系;复旦大学附属肿瘤医院胸外科复旦大学上海医学院肿瘤学系;
【基金】：国家自然科学基金面上项目(81472173)
【分类号】：R734.2
【正文快照】： 肺腺癌是肺癌最常见的组织学类型,其分子生物学特征及组织学特点具有异质性。随着分子生物学技术的不断发展及分子靶向药物的不断问世,除了表皮生长因子受体(epidermalgrowth factor receptor,EGFR)和鼠类肉瘤病毒癌基因(Kirsten rat sarcoma viral oncogene,K-ras)等基因突变

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