Fascin and cyclin D1 immunoreactivity in non-neoplastic vulvar squamous epithelium, vulvar intraepithelial neoplasia and invasive squamous carcinoma: correlation with Ki67 and p16 protein expression.
OBJECTIVE
To investigate cyclin D1 and fascin immunoreactivity in normal, reactive and neoplastic vulvar skin correlating the findings with p16 protein and Ki67 expression.


METHODS
66 vulvar biopsy or resection specimens demonstrating normal appearances, reactive epidermal changes, usual-type vulvar intraepithelial neoplasia (uVIN), differentiated-type VIN (dVIN), p16-positive squamous cell carcinoma (SCC) and p16-negative SCC were examined immunohistochemically for cyclin D1, fascin, Ki67 and p16 protein. Where applicable, expression patterns were compared in microanatomically distinct areas, particularly at the invasive front (deep tumour margin) of SCC.


RESULTS
Normal epidermis showed parabasal Ki67 and cyclin D1 staining while fascin labelled cells in the lower one-third of the epithelium. Reactive and dVIN specimens demonstrated mildly increased Ki67 and cyclin D1 expression that maintained parabasal polarity, whereas uVIN and p16-positive SCC were characterised by loss of cyclin D1 staining. However, in 14 of 20 p16-positive SCC small infiltrative tumour groups and single infiltrating cells at the invasive front showed a cyclin D1-positive/ Ki67-negative phenotype. In contrast, p16-negative SCC generally showed diffuse and concordant cyclin D1 and Ki67 labelling, including at the invasive margin. Fascin expression was increased in all VIN and SCC lesions.


CONCLUSIONS
Variations in cyclin D1 and Ki67 expression between p16-positive and p16-negative vulvar SCCs suggest different mechanisms of invasion in these tumour subgroups. Fascin is upregulated in vulvar squamous neoplasia but immunostaining does not discriminate in situ from invasive lesions nor putative human papilloma virus (HPV)-associated and HPV-independent SCCs.
Department of Histopathology, King Edward Memorial Hospital, , Perth, Western Australia, Australia.
C J R
CJ
Stewart
M L
ML
Crook
D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D002278:Carcinoma in Situ / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D002352:Carrier Proteins / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D015854:Up-Regulation; D014844:Vulva / Q000378:metabolism / Q000473:pathology; D014846:Vulvar Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery
D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen; D008840:Microfilament Proteins; D019938:Cyclin D1; C020324:fascin
Gynaecological Pathology; HPV; Immunohistochemistry; Molecular Pathology; Oncology