title: Clinicopathological analysis of pleomorphic carcinoma of the lung: diffuse ZEB1 expression predicts poor survival.
abstract: OBJECTIVE
  Pleomorphic carcinoma (PC) of the lung is a rare epithelial tumor. The clinicopathological characteristics and prognostic factors of PC are controversial. The information on the ZEB1 gene, which crucially impacts survival of patients with other malignant tumors, is limited for PC.
  
  
  METHODS
  Clinicopathological characteristics of 62 patients with PC were investigated in this study. Associations between immunohistochemical expression of ZEB1 and clinical factors, including patient prognosis, were examined. The patient population consisted of 51 (82.2%) men and 11 (17.8%) women, with a mean age of 65.5 years (range, 31-81 years).
  
  
  RESULTS
  The overall survival rate of the 42 patients, for whom follow-up was available, was 68.3% at 5 years. Using TNM criteria, 7 (11.3%), 11 (17.7%), 3 (4.8%), 21 (33.8%), 15 (24.2%), 2 (3.2%), and 3 (4.8%) patients were classified under pathological stage IA, IB, IIA, IIB, IIIA, IIIB and IV carcinomas, respectively. Fifteen (24.1%) patients had tumors consisting entirely of spindle and giant cells (PC component). The other 47 (75.8%) cancers contained additional carcinoma components (i.e., adenocarcinoma (34/62, 54.8%), squamous cell carcinoma (7/62, 11.3%), adenosquamous carcinoma (4/62, 6.5%) and large cell carcinoma (2/62, 3.2%)). Four of 7 (57.1%) stage IA (<20mm) tumors consisted only of spindle and giant cells. ZEB1 expression was observed only in the PC component. Diffuse expression of ZEB1, was defined as positive nuclear staining in ≥75% of cancer cells, and was found in the PC component in 12 patients. Multivariate analysis revealed that lymph node metastasis, pleural invasion, and diffuse ZEB1 expression in the PC component predicted poorer disease-specific survival (p=0.007, 0.022, and 0.016, respectively).
  
  
  CONCLUSIONS
  This is the first report to indicate that ZEB1 may be used as an immunohistochemical prognosticator of PC, which may be useful for histological assessment of PC in biopsy and surgical specimens.
authors.affiliation: Department of Pathology, Fukuoka University School of Medicine and Hospital, Fukuoka, Japan; Department of General Thoracic, Breast and Pediatric Surgery, Fukuoka University School of Medicine and Hospital, Fukuoka, Japan.
authors.forename: So
authors.initials: S
authors.lastname: Miyahara
authors.affiliation: Department of Pathology, Fukuoka University School of Medicine and Hospital, Fukuoka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hamasaki
authors.affiliation: Department of General Thoracic, Breast and Pediatric Surgery, Fukuoka University School of Medicine and Hospital, Fukuoka, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hamatake
authors.affiliation: Department of General Thoracic, Breast and Pediatric Surgery, Fukuoka University School of Medicine and Hospital, Fukuoka, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Yamashita
authors.affiliation: Department of General Thoracic, Breast and Pediatric Surgery, Fukuoka University School of Medicine and Hospital, Fukuoka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shiraishi
authors.affiliation: Department of General Thoracic, Breast and Pediatric Surgery, Fukuoka University School of Medicine and Hospital, Fukuoka, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Iwasaki
authors.affiliation: Department of Pathology, Fukuoka University School of Medicine and Hospital, Fukuoka, Japan. Electronic address: kaznabes@fukuoka-u.ac.jp.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nabeshima
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D018193:Neoplasms, Complex and Mixed / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D014157:Transcription Factors / Q000235:genetics*; D047368:Tumor Burden; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1
keywords: Immunohistochemistry; Lung cancer; Pleomorphic carcinoma; Prognosis; Transcriptional factors; ZEB1