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

Abstract

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 ≤ 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.