Biomarker-assisted diagnosis of ovarian, cervical and pulmonary small cell carcinomas: the role of TTF-1, WT-1 and HPV analysis

Histopathology. 2007 Sep;51(3):305-12. doi: 10.1111/j.1365-2559.2007.02790.x.


Aims: Small cell carcinoma of the ovary, hypercalcaemic-type (SCCOH) is morphologically similar to small cell carcinomas from other sites. The aims of this study were to (i) determine if a biomarker panel would distinguish small cell carcinomas of the ovary, cervix (SCCCx) and lung (SCCLu) and (ii) potentially determine the histogenesis of SCCOH.

Methods and results: Nine ovarian small cell carcinomas (seven hypercalcaemic type; two pulmonary type), eight SCCCx and 22 SCCLu were immunostained for thyroid transcription factor (TTF)-1, WT-1, p16, cKIT and OCT3/4; a subset of cases were tested for human papillomavirus (HPV). WT-1 was diffusely positive in 6/7 SSCOH versus two of 33 other small cell carcinomas (P <or= 0.001). TTF-1 was diffusely positive in 20/22 SCCLu and 1/8 SCCCx, and negative in all SCCOH. p16 and cKIT demonstrated variable patterns of immunoreactivity in all cases. HPV was identified in 5/6 SCCCx; SCCOH and SCCLu were negative for HPV.

Conclusions: Combined staining with WT-1 and TTF-1 will distinguish SCCOH from SCCLu and SCCCx with a sensitivity of 86% and specificity of 97%. HPV is specific for tumours of cervical origin, but p16 immunohistochemistry is not useful for this purpose. The presence of diffuse WT-1 supports a Müllerian origin for SCCOH, whereas the absence of cKIT and OCT3/4 argues against a germ cell origin.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / analysis*
  • Carcinoma, Small Cell / metabolism
  • Carcinoma, Small Cell / pathology*
  • Carcinoma, Small Cell / virology
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis
  • Diagnosis, Differential
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Nuclear Proteins / analysis
  • Octamer Transcription Factor-3 / analysis
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Papillomaviridae / genetics
  • Papillomaviridae / growth & development
  • Proto-Oncogene Proteins c-kit / analysis
  • Thyroid Nuclear Factor 1
  • Transcription Factors / analysis
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology*
  • Uterine Cervical Neoplasms / virology
  • WT1 Proteins / analysis


  • Biomarkers
  • Cyclin-Dependent Kinase Inhibitor p16
  • NKX2-1 protein, human
  • Nuclear Proteins
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Thyroid Nuclear Factor 1
  • Transcription Factors
  • WT1 Proteins
  • Proto-Oncogene Proteins c-kit