细胞学标本中甲状腺转录因子 1 阴性肺腺癌的分子遗传学改变：具有侵袭性行为和不良预后的亚组。

Molecular genetic alterations in thyroid transcription factor 1-negative lung adenocarcinoma in cytology specimens: A subset with aggressive behavior and a poor prognosis.

机构信息

Division of Cytopathology, Department of Pathology, Johns Hopkins Hospital, Baltimore, Maryland.

Department of Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.

出版信息

Cancer Cytopathol. 2018 Oct;126(10):853-859. doi: 10.1002/cncy.22048. Epub 2018 Sep 10.

DOI:10.1002/cncy.22048

PMID:30199148

Abstract

BACKGROUND

Patients with thyroid transcription factor 1 (TTF1)-negative pulmonary adenocarcinoma (ADC) have been reported to have a worse prognosis and to lack epidermal growth factor receptor (EGFR) mutations. This study describes a series of cytology specimens from patients with clinically confirmed pulmonary carcinoma negative for TTF1.

METHODS

A search for TTF1-negative ADC from 2010 to 2017 was performed. Each patient's clinical history, pathology specimens, and molecular results were noted. Two hundred ten patients with TTF1-positive pulmonary ADC formed the control group.

RESULTS

Fifty specimens were identified from 50 patients (26 females and 24 males). The median age was 58.5 years. The smoking history was as follows: 38 smokers/former smokers (76%), 10 nonsmokers (20%), and 2 patients with an unknown status (4%). Thirty-nine patients (78%) had no previous history of malignancy. The clinical stages were as follows: stage I or II (n = 2 [4%]), stage III (n = 9 [18%]), stage IV (n = 37 [74%]), and unknown (n = 2 [4%]). Patients' mean survival was 10.3 months. Molecular results were available in 43 cases. Twenty-seven cases (63%) had no mutation identified; when they were compared with the control group, TTF1-negative patients had overall shorter survival (P = .0047), even though no statistically significant difference was seen on the clinical stage. Known mutations were less frequent (P = .0095) in TTF-negative tumors (KRAS mutations, n = 11 [25%]; anaplastic lymphoma kinase [ALK], n = 3 [7%]; and EGFR, n = 2 [5%]). This was particularly true for EGFR mutations (P = .047). However, ALK rearrangements were present at an increased frequency in the TTF1-negative group (P = .018).

CONCLUSIONS

Patients with TTF1-negative lung ADC have worse overall survival, a lower frequency of known mutations, and a higher frequency of ALK alterations.

摘要

背景

已有报道称，甲状腺转录因子 1（TTF1）阴性的肺腺癌（ADC）患者预后较差，且缺乏表皮生长因子受体（EGFR）突变。本研究描述了一组来自临床确诊的 TTF1 阴性肺癌患者的细胞学标本。

方法

对 2010 年至 2017 年 TTF1 阴性 ADC 进行检索。记录每位患者的临床病史、病理标本和分子结果。210 例 TTF1 阳性肺 ADC 患者为对照组。

结果

从 50 例患者（26 例女性和 24 例男性）中鉴定出 50 个标本。中位年龄为 58.5 岁。吸烟史如下：38 例吸烟者/戒烟者（76%），10 例非吸烟者（20%），2 例患者吸烟史不明（4%）。39 例（78%）患者无既往恶性肿瘤病史。临床分期如下：Ⅰ期或Ⅱ期（n=2，4%），Ⅲ期（n=9，18%），Ⅳ期（n=37，74%），未知分期（n=2，4%）。患者的平均生存时间为 10.3 个月。43 例患者有分子检测结果。27 例（63%）未发现突变；与对照组相比，TTF1 阴性患者的总生存期更短（P=0.0047），尽管在临床分期上无统计学差异。TTF1 阴性肿瘤中罕见已知突变（P=0.0095）：KRAS 突变 11 例（25%），间变性淋巴瘤激酶（ALK）突变 3 例（7%），EGFR 突变 2 例（5%）。EGFR 突变的差异尤其明显（P=0.047）。然而，TTF1 阴性组中 ALK 重排的发生率更高（P=0.018）。