Clinicopathological analysis of pleomorphic carcinoma of the lung: diffuse ZEB1 expression predicts poor survival

Lung Cancer. 2015 Jan;87(1):39-44. doi: 10.1016/j.lungcan.2014.11.007. Epub 2014 Nov 15.

Abstract

Objectives: 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.

Materials and 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).

Conclusion: 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.

Keywords: Immunohistochemistry; Lung cancer; Pleomorphic carcinoma; Prognosis; Transcriptional factors; ZEB1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Gene Expression*
  • Homeodomain Proteins / genetics*
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Neoplasms, Complex and Mixed / drug therapy
  • Neoplasms, Complex and Mixed / genetics*
  • Neoplasms, Complex and Mixed / mortality
  • Neoplasms, Complex and Mixed / pathology*
  • Prognosis
  • Transcription Factors / genetics*
  • Tumor Burden
  • Zinc Finger E-box-Binding Homeobox 1

Substances

  • Homeodomain Proteins
  • Transcription Factors
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1