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Clinical impact of PD-L1 and PD-1 expression in squamous cell cancer of the vulva

  • Fabinshy ThangarajahEmail author
  • Bernd Morgenstern
  • Caroline Pahmeyer
  • Lars Mortimer Schiffmann
  • Julian Puppe
  • Peter Mallmann
  • Stefanie Hamacher
  • Reinhard Buettner
  • Christina Alidousty
  • Barbara Holz
  • Andreas H. Scheel
  • Anne Maria SchultheisEmail author
Original Article – Clinical Oncology
  • 67 Downloads

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.

Keywords

Vulvar carcinoma PD-L1 PD-1 HPV 

Notes

Compliance with ethical standards

Conflict of interest

AMS, CA und BH are supported by Roche Pharma AG and Kölner Krebsstiftung. JP was supported by the Else Kröner-Fresenius Stiftung (EKFS-2014-A06 and 2016 Kolleg.19). AHS and RB have participated in advisory boards for BMS, MSD and F. Hoffmann-La Roche AG, pharmaceutical division. FT declares that she has no conflict of interest. BM declares that he has no conflict of interest. CP declares that she has no conflict of interest. LMS declares that he has no conflict of interest. PM declares that he has no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Fabinshy Thangarajah
    • 1
    Email author
  • Bernd Morgenstern
    • 1
  • Caroline Pahmeyer
    • 1
  • Lars Mortimer Schiffmann
    • 2
  • Julian Puppe
    • 1
  • Peter Mallmann
    • 1
  • Stefanie Hamacher
    • 3
  • Reinhard Buettner
    • 4
  • Christina Alidousty
    • 4
  • Barbara Holz
    • 4
  • Andreas H. Scheel
    • 4
  • Anne Maria Schultheis
    • 4
    Email author
  1. 1.Department of Obstetrics and Gynaecology, Medical Faculty, University Hospital CologneUniversity of CologneCologneGermany
  2. 2.Department of General, Visceral and Cancer SurgeryUniversity of CologneCologneGermany
  3. 3.Institute of Medical Statistics and Computational BiologyUniversity Hospital CologneCologneGermany
  4. 4.Department of Pathology, University Hospital of CologneInstitute of PathologyCologneGermany

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