title: KRAS mutation-positive bronchial surface epithelium (BSE)-type lung adenocarcinoma with strong expression of TTF-1: a case providing a further insight as for the role of TTF-1 in the oncogenesis.
abstract: Bronchial surface epithelium (BSE)-type lung adenocarcinoma is a subtype of non-terminal respiratory unit (TRU)-type lung adenocarcinoma originating in the bronchial surface epithelium. However, there are few known cases of BSE-type adenocarcinoma with marked expression of thyroid transcription factor-1 (TTF-1). This paper describes a very rare case of KRAS mutation-positive BSE-type adenocarcinoma that exhibited strong expression of TTF-1 that was putatively involved in oncogenesis. An 84-year-old woman, a never smoker, was referred to our hospital because of an abnormal chest radiograph. Chest computed tomography (CT) showed a solid mass lesion, 15 mm × 10 mm, with a relatively smooth margin in the left upper lobe. The patient underwent partial resection of the left upper lobe for strongly suspected lung cancer with a clinical stage of cT1aN0M0. Histopathological findings showed continuous migration of papillary, hyperplastic, atypical columnar tumor cells originating from normal bronchial surface epithelium, leading to a diagnosis of BSE-type adenocarcinoma. TTF-1 was strongly expressed in almost 100% of the tumor cells, which tested positive for the KRAS mutation. TTF-1 has recently attracted attention as an oncogene, and it is purportedly involved in the carcinogenesis and survival of lung adenocarcinoma cells. There is typically an inverse correlation between the respective expressions of KRAS and TTF-1, but in the present study, they appeared simultaneously and were both putatively involved as oncogenic driver alterations. This case is important in that it sheds some light on the largely unknown pathogenic mechanism of BSE-type adenocarcinoma.
authors.affiliation: Department of Thoracic Surgery, Fujieda Municipal General Hospital Fujieda, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takanashi
authors.affiliation: Department of Pathology, University of Tokyo, Graduate School of Medicine Tokyo, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Tajima
authors.affiliation: Department of Thoracic Surgery, Fujieda Municipal General Hospital Fujieda, Japan.
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Hayakawa
authors.affiliation: Department of Thoracic Surgery, Fujieda Municipal General Hospital Fujieda, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Neyatani
authors.affiliation: Department of Surgery 1, Hamamatsu University School of Medicine Hamamatsu, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Funai
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics*; D001706:Biopsy; D063646:Carcinogenesis / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D004252:DNA Mutational Analysis; D004847:Epithelial Cells / Q000737:chemistry* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D009154:Mutation; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis*; D011013:Pneumonectomy; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D000074482:Thyroid Nuclear Factor 1; D014057:Tomography, X-Ray Computed; D014157:Transcription Factors / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: BSE-type adenocarcinoma; KRAS; TTF-1
references.citation: Lung Cancer. 2014 Jun;84(3):281-8
references.pmid: 24725383
references.citation: Am J Surg Pathol. 2002 Jun;26(6):767-73
references.pmid: 12023581
references.citation: Cancer Res. 2004 Dec 15;64(24):8919-23
references.pmid: 15604253
references.citation: Am J Surg Pathol. 2005 May;29(5):633-9
references.pmid: 15832087
references.citation: Mod Pathol. 2012 Sep;25(9):1265-74
references.pmid: 22555174
references.citation: J Clin Oncol. 2006 Apr 10;24(11):1679-88
references.pmid: 16549822
references.citation: J Biol Chem. 2013 Aug 30;288(35):24992-5000
references.pmid: 23818522
references.citation: Nature. 2007 Dec 6;450(7171):893-8
references.pmid: 17982442
references.citation: Pathol Int. 2008 Jan;58(1):31-7
references.pmid: 18067638
references.citation: Oncogene. 2008 Jun 5;27(25):3635-40
references.pmid: 18212743
references.citation: Clin Sci (Lond). 2009 Jan;116(1):27-35
references.pmid: 19037882
references.citation: Cancer Res. 2005 Jun 15;65(12):5076-83
references.pmid: 15958551
references.citation: Cancer Cell. 2013 Jun 10;23(6):718-23
references.pmid: 23763999
references.citation: Cancer Res. 2007 Jul 1;67(13):6007-11
references.pmid: 17616654