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Molecular genetic alterations in thyroid transcription factor 1–negative lung adenocarcinoma in cytology specimens: A subset with aggressive behavior and a poor prognosis
Author(s) -
Rodriguez Erika F.,
VandenBussche Christopher J.,
Chowsilpa Sayanan,
Maleki Zahra
Publication year - 2018
Publication title -
cancer cytopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.29
H-Index - 57
eISSN - 1934-6638
pISSN - 1934-662X
DOI - 10.1002/cncy.22048
Subject(s) - medicine , adenocarcinoma , anaplastic lymphoma kinase , kras , lung cancer , stage (stratigraphy) , ros1 , gastroenterology , malignancy , lung , oncology , carcinoma , pathology , cancer , paleontology , colorectal cancer , biology , malignant pleural effusion
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.