Fabinshy Thangarajah1, Bernd Morgenstern2, Caroline Pahmeyer2, Lars Mortimer Schiffmann3, Julian Puppe2, Peter Mallmann2, Stefanie Hamacher4, Reinhard Buettner5, Christina Alidousty5, Barbara Holz5, Andreas H Scheel5, Anne Maria Schultheis6. 1. Department of Obstetrics and Gynaecology, Medical Faculty, University Hospital Cologne, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany. Fabinshy.Thangarajah@uk-koeln.de. 2. Department of Obstetrics and Gynaecology, Medical Faculty, University Hospital Cologne, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany. 3. Department of General, Visceral and Cancer Surgery, University of Cologne, Kerpener Straße 62, 50937, Cologne, Germany. 4. Institute of Medical Statistics and Computational Biology, University Hospital Cologne, Kerpener Straße 62, 50937, Cologne, Germany. 5. Department of Pathology, University Hospital of Cologne, Institute of Pathology, Kerpener Str. 62, 50937, Cologne, Germany. 6. Department of Pathology, University Hospital of Cologne, Institute of Pathology, Kerpener Str. 62, 50937, Cologne, Germany. Anne.Schultheis@uk-koeln.de.
Abstract
PURPOSE: Squamous cell carcinoma of the vulva (SQCV) is the fifth most common cancer in women and accounts for about 5% of all genital cancers in women. The PD-L1 signaling pathway is activated in many malignant neoplasms and its blockade enhances anti-cancer immunity. The aim of our study was to examine the protein expression of PD-L1 and PD-1 in squamous cell cancer of the vulva, its correlations with clinicopathologic features and prognostic value. METHODS: Patients with SQCV treated in one institution were used for the analyses. PD-L1 immunohistochemistry was performed on 4 µm-thick section of the respective FFPE tissue blocks using the 28-8 antibody. PD-L1 scoring was performed separately for tumour cells (TC) and tumour associated immune cells. DNA was extracted to determine HPV status. Kaplan-Meier estimates for disease-free-survival and overall-survival were calculated and compared by log-rank test. RESULTS: PD-L1 expression in tumour cells could be observed in 32.9% of the patients. The expression of PD-L1 in peritumoural immune cells was confirmed in 91.4% of the patients. A significant correlation between PD-L1 expression in tumour cells and tumour stage was detected (p = 0.007). PD-L1 expression was independent from HPV status. Using the log-rank test we could not prove any significant differences in disease-free survival (p = 0.434) and overall survival (p = 0.858). Regression analysis showed that nodal status is a predictive factor of survival (p < 0.001). CONCLUSION: The present study showed that a relevant amount of patients with squamous cell cancer of the vulva express PD-L1 in both, tumour cells and tumour-associated immune cells. Furthermore, the significant correlation of PD-L1 expression in TCs with tumour stage indicated the clinical impact of PD-L1 expression during tumour development. These data indicate that SQCV might be amenable to immune checkpoint-inhibition and constitute a rational for the future clinical trials.
PURPOSE:Squamous cell carcinoma of the vulva (SQCV) is the fifth most common cancer in women and accounts for about 5% of all genital cancers in women. The PD-L1 signaling pathway is activated in many malignant neoplasms and its blockade enhances anti-cancer immunity. The aim of our study was to examine the protein expression of PD-L1 and PD-1 in squamous cell cancer of the vulva, its correlations with clinicopathologic features and prognostic value. METHODS:Patients with SQCV treated in one institution were used for the analyses. PD-L1 immunohistochemistry was performed on 4 µm-thick section of the respective FFPE tissue blocks using the 28-8 antibody. PD-L1 scoring was performed separately for tumour cells (TC) and tumour associated immune cells. DNA was extracted to determine HPV status. Kaplan-Meier estimates for disease-free-survival and overall-survival were calculated and compared by log-rank test. RESULTS:PD-L1 expression in tumour cells could be observed in 32.9% of the patients. The expression of PD-L1 in peritumoural immune cells was confirmed in 91.4% of the patients. A significant correlation between PD-L1 expression in tumour cells and tumour stage was detected (p = 0.007). PD-L1 expression was independent from HPV status. Using the log-rank test we could not prove any significant differences in disease-free survival (p = 0.434) and overall survival (p = 0.858). Regression analysis showed that nodal status is a predictive factor of survival (p < 0.001). CONCLUSION: The present study showed that a relevant amount of patients with squamous cell cancer of the vulva express PD-L1 in both, tumour cells and tumour-associated immune cells. Furthermore, the significant correlation of PD-L1 expression in TCs with tumour stage indicated the clinical impact of PD-L1 expression during tumour development. These data indicate that SQCV might be amenable to immune checkpoint-inhibition and constitute a rational for the future clinical trials.
Authors: Elysha Kolitz; Elena Lucas; Gregory A Hosler; Jiwoong Kim; Suntrea Hammer; Cheryl Lewis; Lin Xu; Andrew T Day; Melissa Mauskar; Jayanthi S Lea; Richard C Wang Journal: J Invest Dermatol Date: 2021-10-28 Impact factor: 7.590
Authors: Kim E Kortekaas; Saskia J Santegoets; Ziena Abdulrahman; Vanessa J van Ham; Marij van der Tol; Ilina Ehsan; Helena C van Doorn; Tjalling Bosse; Mariëtte I E van Poelgeest; Sjoerd H van der Burg Journal: J Immunother Cancer Date: 2019-09-03 Impact factor: 13.751
Authors: Priyadharsini Nagarajan; Christian El-Hadad; Stephen K Gruschkus; Jing Ning; Courtney W Hudgens; Oded Sagiv; Neil Gross; Michael T Tetzlaff; Bita Esmaeli Journal: Invest Ophthalmol Vis Sci Date: 2019-05-01 Impact factor: 4.799