Abstract
The immune checkpoint protein programmed death ligand-1 (PD-L1) is expressed in different types of cancer and is a potential prognostic factor as well as therapeutic target. This study evaluated PD-L1 expression in the neoplastic progression of vulvar epithelia with respect to the pattern of infiltration in FIGO stages I keratinizing squamous cell carcinomas (SCC). Normal squamous vulvar epithelia (n=20), usual type vulvar intraepithelial neoplasia (uVIN, n=23), differentiated VIN (dVIN, n=21) and FIGO stage I SCC (n=35) were immunostained for PD-L1. In SCC a cohesive growth with well-delineated borders was considered as pushing, dissociative growth in small groups or single cells was defined as diffuse pattern of infiltration. Immunostaining was done with a monoclonal anti PD-L1 antibody (clone SP263, Ventana) and scored to determine up-regulation and overexpression (score 0/1+, 0-5% immunoreactive cells; score 2+, >5 to 50% immunoreactive cells; score 3+, >50% immunoreactive cells). PD-L1 immunoexpression was comparable in normal epithelia and VINs (score 0/1+, n=59; score 2+, n=5, in VINs only; score 3+, n=0), was significantly increased (P<0.0001) in SCC (score 0/1+, n=13; score 2+, n=16; score 3+, n=6), and was related to a diffuse pattern of infiltration (P<0.0001). Staining was accentuated at the invasive margins of SCC frequently. PD-L1 expression is up-regulated in the neoplastic cells of vulvar low stage SCC, related to the development of an invasive phenotype reflecting the initiation of cancer immunoediting, and to an aggressive diffuse type of stromal invasion.
Highlights
Invasive squamous cell carcinoma (SCC) is the most common type of all invasive vulvar cancers
This study investigated the epithelial expression of Programmed Death Ligand-1 (PD-L1) in the described epithelia; tumor- infiltrating immune cells were scored using the same criteria as in neoplastic epithelial tissues
PD-L1 which is expressed in many cancer cells, prevents tumor death by blocking T cell activity and has been shown a predictive biomarker in cancer immunotherapy.[8,19]
Summary
Invasive squamous cell carcinoma (SCC) is the most common type of all invasive vulvar cancers. Programmed Death Ligand-1 (PD-L1) expression is up-regulated and related to the pattern of invasion in FIGO Stage I vulvar squamous cell carcinomas. Basaloid and warty (condylomatous) or usual subtypes of VIN (uVIN) are associated with relatively younger women, and evidence of human papillomavirus (HPV) nucleic acids. Keratinizing SCC is frequently found in women older than 55 years, is usually unrelated to HPV infection, but may be associated with dVIN and lichen sclerosus. This type of SCC accounts for 65% of vulvar invasive SCC and marks another pathway in the development of these tumors.[1]. Cohorts of early stage vulvar HPVindependent SCC and dVIN as well as uVIN were analysed to study and compare the epithelial PD-L1 immunoexpression in intraepithelial as well as early invasive neoplastic tissues
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