title: Distinct Characteristics of Small Cell Lung Cancer Correlate With Central or Peripheral Origin: Subtyping Based on Location and Expression of Transcription Factor TTF-1.
abstract: Small-cell lung carcinoma (SCLC) is a type of lung cancer with neuroendocrine differentiation and a poor prognosis that is widely believed to arise in the central lung. Thyroid transcription factor-1 (TTF-1) is a peripheral marker of lung adenocarcinoma that is also highly expressed in SCLC. In this study, we examined whether SCLC is really a central-type tumor and the relationship between tumor location, TTF-1 expression and prognosis of SCLC.Ninety six SCLCs, diagnosed from biopsies or surgical materials, for which detailed computed tomography (CT) images were available, were collected consecutively from Japanese patients between 2004 and 2011. We examined the location of the primary tumor (central or peripheral) using thin-sliced CT, a TTF-1 immunohistochemical expression, and clinicopathology including prognosis.Of the 96 SCLCs, 74% (71/96) were of the peripheral type and found to have a significantly worse prognosis than central-type tumors. TTF-1 immunoreactivity was identified in 79 tumors (82%), 78% of which (62/79) were of the peripheral type and 22% of which were central. TTF-1 expression was significantly correlated with peripheral location (P = 0.030). Multivariate analysis revealed that high TNM stages and the peripheral location were independent markers for poor survival.The majority of SCLCs were of the peripheral type. The peripheral-type SCLC expressed TTF-1 more frequently and had a poorer prognosis than central-type tumors did. Further analysis on original sites of SCLC, using molecular methodology, or based on another ethnicity, should be warranted.
authors.affiliation: From the Division of Pathology, The Cancer Institute, Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research (JFCR) (EM, NM, HO, HN, YI); Thoracic Center, The Cancer Institute Hospital, JFCR, Tokyo (FO, MN, SO); and Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan (EM, MI).
authors.forename: Eisaku
authors.initials: E
authors.lastname: Miyauchi
authors.forename: Noriko
authors.initials: N
authors.lastname: Motoi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ono
authors.forename: Hironori
authors.initials: H
authors.lastname: Ninomiya
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Ohyanagi
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishio
authors.forename: Sakae
authors.initials: S
authors.lastname: Okumura
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ichinose
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishikawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008175:Lung Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000096:biosynthesis*; D011379:Prognosis; D055752:Small Cell Lung Carcinoma / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000473:pathology*; D012907:Smoking / Q000453:epidemiology; D000074482:Thyroid Nuclear Factor 1; D014057:Tomography, X-Ray Computed; D014157:Transcription Factors / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors