中华病理学杂志
中華病理學雜誌
중화병이학잡지
Chinese Journal of Pathology
2011年
10期
655-659
,共5页
孙孟红%杨飞%沈磊%张玲%陈颖%蔡旭%朱晓丽%周晓燕
孫孟紅%楊飛%瀋磊%張玲%陳穎%蔡旭%硃曉麗%週曉燕
손맹홍%양비%침뢰%장령%진영%채욱%주효려%주효연
癌,非小细胞肺%受体,表皮生长因子%突变
癌,非小細胞肺%受體,錶皮生長因子%突變
암,비소세포폐%수체,표피생장인자%돌변
Carcinoma,non-small-cell lung%Receptor,epidermal growth factor%Mutation
目的回顾性分析非小细胞肺癌(NSCLC)中采用直接测序法检测的表皮生长因子受体(EGFR)基因突变率、突变分布特征及其与临床病理的相关性。方法收集NSCLC共443例，其中包括手术切除样本299例、粗针穿刺活检标本59例、细针穿刺和胸腔积液细胞学样本85例。所有样本均通过石蜡包埋、切片后确定肿瘤细胞含量，显微切割富集肿瘤细胞后采用聚合酶链反应-直接测序法检测EGFR基因酪氨酸激酶编码区第18至21号外显子的突变。结果(1)在443例NSCLC标本中共检出EGFR基因突变193个，发生在189例患者中(42.7％)；EGFR基因第18至21号外显子的突变率分别为2.0％( 4/193)、48.7％ (94/193)、6.7％ (13/193)和42.5％ (82/193)；(2)EGFR基因总突变率与年龄无显著相关性，但在年龄大于中位年龄（57岁）的患者中第21号外显子的突变率(50.9％，54/106)高于年龄小于或等于中位年龄者(32.2％，28/87；P＜0.01)；(3)女性患者中EGFR基因突变率(53.5％,107/200)高于男性患者突变率(33.7％，82/243；P ＜0.01)；(4)腺癌中的突变率(46.5％，161/346)高于鳞癌(13.3％，4/30；P＜0.01)和低分化癌者(24.1％，7/29；P＜0.05)，而与腺鳞癌(7/13)差异无统计学意义(P＞0.05)；(5)在手术切除、粗针穿刺活检以及细针穿刺和胸腔积液细胞学样本中EGFR突变检出率有逐渐下降的趋势，分别为49.5％( 148/299)、35.6％ (21/59)和23.5％ (20/85)，其中细针穿刺和胸腔积液的细胞学样本中的检出率较手术标本中的检出率为低(P＜0.01)。结论直接测序法是检测NSCLC中EGFR基因突变的有效方法，特别对未知突变类型的检出具有优势；NSCLC中EGFR基因突变在女性和腺癌中多见，以第19号外显子的缺失突变和第21号外显子的点突变为主；EGFR基因突变分布特征可能与年龄有一定关系；EGFR基因突变检出率与样本类型密切相关，活检组织及细胞学样本是检测EGFR基因突变的有用材料，但可能会漏检部分患者中EGFR基因的突变。
目的迴顧性分析非小細胞肺癌(NSCLC)中採用直接測序法檢測的錶皮生長因子受體(EGFR)基因突變率、突變分佈特徵及其與臨床病理的相關性。方法收集NSCLC共443例，其中包括手術切除樣本299例、粗針穿刺活檢標本59例、細針穿刺和胸腔積液細胞學樣本85例。所有樣本均通過石蠟包埋、切片後確定腫瘤細胞含量，顯微切割富集腫瘤細胞後採用聚閤酶鏈反應-直接測序法檢測EGFR基因酪氨痠激酶編碼區第18至21號外顯子的突變。結果(1)在443例NSCLC標本中共檢齣EGFR基因突變193箇，髮生在189例患者中(42.7％)；EGFR基因第18至21號外顯子的突變率分彆為2.0％( 4/193)、48.7％ (94/193)、6.7％ (13/193)和42.5％ (82/193)；(2)EGFR基因總突變率與年齡無顯著相關性，但在年齡大于中位年齡（57歲）的患者中第21號外顯子的突變率(50.9％，54/106)高于年齡小于或等于中位年齡者(32.2％，28/87；P＜0.01)；(3)女性患者中EGFR基因突變率(53.5％,107/200)高于男性患者突變率(33.7％，82/243；P ＜0.01)；(4)腺癌中的突變率(46.5％，161/346)高于鱗癌(13.3％，4/30；P＜0.01)和低分化癌者(24.1％，7/29；P＜0.05)，而與腺鱗癌(7/13)差異無統計學意義(P＞0.05)；(5)在手術切除、粗針穿刺活檢以及細針穿刺和胸腔積液細胞學樣本中EGFR突變檢齣率有逐漸下降的趨勢，分彆為49.5％( 148/299)、35.6％ (21/59)和23.5％ (20/85)，其中細針穿刺和胸腔積液的細胞學樣本中的檢齣率較手術標本中的檢齣率為低(P＜0.01)。結論直接測序法是檢測NSCLC中EGFR基因突變的有效方法，特彆對未知突變類型的檢齣具有優勢；NSCLC中EGFR基因突變在女性和腺癌中多見，以第19號外顯子的缺失突變和第21號外顯子的點突變為主；EGFR基因突變分佈特徵可能與年齡有一定關繫；EGFR基因突變檢齣率與樣本類型密切相關，活檢組織及細胞學樣本是檢測EGFR基因突變的有用材料，但可能會漏檢部分患者中EGFR基因的突變。
목적회고성분석비소세포폐암(NSCLC)중채용직접측서법검측적표피생장인자수체(EGFR)기인돌변솔、돌변분포특정급기여림상병리적상관성。방법수집NSCLC공443례，기중포괄수술절제양본299례、조침천자활검표본59례、세침천자화흉강적액세포학양본85례。소유양본균통과석사포매、절편후학정종류세포함량，현미절할부집종류세포후채용취합매련반응-직접측서법검측EGFR기인락안산격매편마구제18지21호외현자적돌변。결과(1)재443례NSCLC표본중공검출EGFR기인돌변193개，발생재189례환자중(42.7％)；EGFR기인제18지21호외현자적돌변솔분별위2.0％( 4/193)、48.7％ (94/193)、6.7％ (13/193)화42.5％ (82/193)；(2)EGFR기인총돌변솔여년령무현저상관성，단재년령대우중위년령（57세）적환자중제21호외현자적돌변솔(50.9％，54/106)고우년령소우혹등우중위년령자(32.2％，28/87；P＜0.01)；(3)녀성환자중EGFR기인돌변솔(53.5％,107/200)고우남성환자돌변솔(33.7％，82/243；P ＜0.01)；(4)선암중적돌변솔(46.5％，161/346)고우린암(13.3％，4/30；P＜0.01)화저분화암자(24.1％，7/29；P＜0.05)，이여선린암(7/13)차이무통계학의의(P＞0.05)；(5)재수술절제、조침천자활검이급세침천자화흉강적액세포학양본중EGFR돌변검출솔유축점하강적추세，분별위49.5％( 148/299)、35.6％ (21/59)화23.5％ (20/85)，기중세침천자화흉강적액적세포학양본중적검출솔교수술표본중적검출솔위저(P＜0.01)。결론직접측서법시검측NSCLC중EGFR기인돌변적유효방법，특별대미지돌변류형적검출구유우세；NSCLC중EGFR기인돌변재녀성화선암중다견，이제19호외현자적결실돌변화제21호외현자적점돌변위주；EGFR기인돌변분포특정가능여년령유일정관계；EGFR기인돌변검출솔여양본류형밀절상관，활검조직급세포학양본시검측EGFR기인돌변적유용재료，단가능회루검부분환자중EGFR기인적돌변。
Objective To retrospectively analyze epidermal growth factor receptor (EGFR) gene mutation frequencies and distribution characteristics in Chinese patients with non-small-cell lung carcinoma (NSCLC) by direct gene sequencing. Methods Clinical samples from 443 NSCLC patients were obtained for EGFR gene mutation analysis, including 299 surgical specimens, 59 core biopsies and 85 fine needle aspiration and pleural effusion cytology specimens. All samples were processed from paraffin embedded blocks and microdissection was performed to enrich tumor cells. PCR based direct gene sequencing was used to investigate tyrosine kinase domain coding region involving exon 18 through 21. Results ( 1 ) Among 443 samples, 193 mutations were detected in 189 patients (42.7％ ) and 4 patients possessed two mutations involving two different exons in their tumor samples. The percentage of mutations involving exon 18 to 21 were 2.0％ (4/193) ,48.7％ (94/193) ,6.7％ (13/193) and 42.5％ (82/193) respectively. (2) There was no significant correlation of EGFR mutation with age, however, mutation rate (50.9％, 54/106) of exon 21 in patients over median age 57 was higher than that of the younger patients (32.2％ ,28/87;P ＜0.01 ). (3) EGFR mutation rate was remarkably higher in female patients (53.5％ ,107/200) than in male patients (33.7％ ,82/243 ; P ＜ 0.01 ). ( 4 ) Mutation rate in adenocarcinomas (46.5％, 161/346 ) was much higher than in squamous cell carcinomas (13.3％, 4/30) and poorly differentiated carcinomas (24.1％ ,7/29 ;P ＜ 0.01, P ＜0.05 ), while the adenosquamous carcinomas shared a mutation rate similar to that of adenocarcinoma (7/13, P ＞0.05). (5) In surgical samples, core biopsies and cytological samples, the EGFR mutation detection rates were 49.5％ (148/299) ,35.6％ (21/59)and 23.5％ (20/85)respectively. The fine needle aspiration and cytological samples showed much lower EGFR mutation detection rates (23.5％ ,20/85 ) than that of surgical samples (49.5％, 148/299 ; P ＜ 0.01 ). Conclusions ( 1 )Direct gene sequencing is a reliable and effective method for the detection of EGFR mutations in NSCLC,particularly for unknown EGFR mutations. (2) EGFR mutations are more frequent in female patients and patients with adenocarcinoma NSCLC, involving mainly exon 19 and 21. (3) The mutation distribution in exons of EGFR gene appears age-related. (4) Detection rate of EGFR mutation varies in different sample types. Small biopsy and fine needle aspiration specimens are valuable materials for analyzing EGFR mutation in NSCLC, although rare false negativity may occur using such samples.
