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

• Published in: Histopathology Vol. 51; no. 3; pp. 305 - 312
• Main Authors: Carlson, J W, Nucci, M R, Brodsky, J, Crum, C P, Hirsch, M S
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2007; Blackwell
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers - analysis; Carcinoma, Small Cell - metabolism; Carcinoma, Small Cell - pathology; Carcinoma, Small Cell - virology; cervix; cKIT; Cyclin-Dependent Kinase Inhibitor p16 - analysis; Diagnosis, Differential; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; HPV; Human papillomavirus; Humans; hypercalcaemic; Immunohistochemistry; In Situ Hybridization; Investigative techniques, diagnostic techniques (general aspects); lung; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Medical sciences; Middle Aged; Nuclear Proteins - analysis; OCT3/4; Octamer Transcription Factor-3 - analysis; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; ovary; p16; Papillomaviridae - genetics; Papillomaviridae - growth & development; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Proto-Oncogene Proteins c-kit - analysis; small cell carcinoma; Thyroid Nuclear Factor 1; Transcription Factors - analysis; TTF-1; Tumors; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - virology; WT-1; WT1 Proteins - analysis; Lung; Biological marker; Papovaviridae; Respiratory system; hypercalcaemic; CDKN2 gene; HPV; Papillomavirus; Ovary; Human papillomavirus; p16; Female genital system; Diagnosis; Small cell carcinoma; cKIT; Tumor suppressor gene; cervix; Biological indicator; WT-1; Malignant tumor; TTF-1; Female genital diseases; Virus; Anatomic pathology; Cervix carcinoma; OCT3/4; Uterine cervix diseases; Cervical cancer
• ISSN: 0309-0167; 1365-2559
• 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 ≤ 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.