肺腺癌转移中病理亚型的临床相关性。

The clinical relevance of pathologic subtypes in metastatic lung adenocarcinoma.

机构信息

*Department of Medical Oncology, St. Vincent's Hospital, Melbourne; †Department of Medicine, University of Melbourne; ‡Translational Genomics and Epigenomics Laboratory, Ludwig Institute for Cancer Research, Olivia Newton John Cancer and Wellness Centre, Heidelberg; §Department of Pathology, University of Melbourne; ‖Department of Medicine, Eastern Hill Academic Centre, Melbourne Medical School, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne; ¶Department of Respiratory Medicine, St. Vincent's Hospital; #Department of Thoracic Surgery, St. Vincent's Hospital, Melbourne; **Department of Surgery, University of Melbourne; and ††Department of Anatomical Pathology, St. Vincent's Hospital, Melbourne, Australia.

出版信息

J Thorac Oncol. 2014 May;9(5):654-63. doi: 10.1097/JTO.0000000000000150.

DOI:10.1097/JTO.0000000000000150

PMID:24722155

Abstract

INTRODUCTION

The International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification of lung adenocarcinoma recommends identification of pathologic patterns in metastatic samples where possible. We investigated the clinical relevance of these patterns.

METHODS

Patients with a surgical biopsy of lung adenocarcinoma from a metastatic site were included. Slides were reviewed by an anatomical pathologist identifying the histologic patterns of solid with mucin, acinar, micropapillary, papillary, and assigning a major adenocarcinoma subtype according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. EGFR and KRAS mutation testing were performed on formalin-fixed, paraffin-embedded blocks. Mutations were detected by high resolution melting assay with high resolution melting-positive samples confirmed by Sanger sequencing.

RESULTS

One-hundred patients were included. The major histologic subtype prevalence was as follows: solid (50), acinar (29), micropapillary (20), and papillary (1). Of 100 patients, 45 received no systemic therapy with no overall survival differences seen by histologic subtype and 55 received systemic therapy (chemoradiotherapy with curative intent or palliative chemotherapy). Worse survival was seen in the major solid histologic subtype compared with major acinar (hazard ratio 0.32 [95% confidence interval 0.15-0.68], p = 0.003) and micropapillary subtypes (hazard ratio 0.34 [95% confidence interval, 0.17-0.69], p = 0.003). The major solid histologic subtype was less likely to harbor EGFR mutations (p = 0.006) and was less frequent in never smokers (p = 0.010) compared with other histologic subtypes.

CONCLUSION

The major solid histologic subtype of lung adenocarcinoma at metastatic sites is associated with shorter overall survival on systemic anticancer therapy. Furthermore, the major solid histologic subtype is less likely to harbor EGFR mutations. These results require validation in larger cohorts.

摘要

简介

国际肺癌研究协会/美国胸科学会/欧洲呼吸学会的肺癌腺癌分类建议尽可能在转移样本中识别病理模式。我们研究了这些模式的临床相关性。

方法

纳入了在转移性部位进行肺腺癌手术活检的患者。由解剖病理学家对切片进行复查，确定实体伴黏液、腺泡、微乳头状、乳头状的组织学模式，并根据国际肺癌研究协会/美国胸科学会/欧洲呼吸学会分类指定主要腺癌亚型。对福尔马林固定、石蜡包埋的组织块进行 EGFR 和 KRAS 基因突变检测。通过高分辨率熔解分析检测突变，对高分辨率熔解阳性的样本用 Sanger 测序进行确认。

结果

共纳入 100 例患者。主要组织学亚型的患病率如下：实体型（50%）、腺泡型（29%）、微乳头状型（20%）和乳头状型（1%）。在 100 例患者中，45 例未接受全身治疗，不同组织学亚型的总生存期无差异，55 例接受全身治疗（有治愈意图的放化疗或姑息化疗）。与主要腺泡型（风险比 0.32 [95%置信区间 0.15-0.68]，p = 0.003）和微乳头状型（风险比 0.34 [95%置信区间 0.17-0.69]，p = 0.003）相比，主要实体型的生存较差。主要实体型组织学亚型更不可能携带 EGFR 突变（p = 0.006），并且与其他组织学亚型相比，在从不吸烟者中更为少见（p = 0.010）。