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The vulvar immunohistochemical panel (VIP) project: molecular profiles of vulvar Paget’s disease

  • Giorgia Garganese
  • Frediano Inzani
  • Giulia Mantovani
  • Angela Santoro
  • Michele Valente
  • Gabriele Babini
  • Giuliana Petruzzellis
  • Simona Maria FragomeniEmail author
  • Stefano Gentileschi
  • Sonia Bove
  • Massimo Franchi
  • Giuseppe Angelico
  • Anna Fagotti
  • Giovanni Scambia
  • Gian Franco Zannoni
Original Article – Cancer Research

Abstract

Purpose

To investigate the expression of biological markers in primary vulvar Paget’s disease (VPD).

Methods

Forty-one patients referred to a single major Center for Gynecologic Oncology from January 2008 to June 2018 were enrolled retrospectively: 30 non-invasive-VPD and 11 invasive-VPD. A total number of 60 samples, from all the 41 vulvar sites (VS), 8 metastatic lymph node sites (MLS) and 11 successive recurrent disease in vulvar site (RVS), were tested for an immunohistochemical panel, including the following markers: PD-L1, CD3, MSH2, MSH6, MLH1, PMS2, HER2/neu, EGFR, p16, p53, Ki67, ER, PR, AR, VEGF and CD31.

Results

We found a positive PD-L1 in 10% of non-invasive-VPD and 27% of invasive-VPD (18% VS; 38% MLS). ER and AR were expressed respectively in more than 70% and 75% of all specimens. HER2/neu amplification was found in 21% of non-invasive-VPD and 45% of invasive-VPD (40% VS; 38% MLS). A machine learning cluster analysis identified three groups among non- invasive-VPD: cluster-1 with higher median ER expression (40%); cluster-3 with more frequent HER2/neu overexpression (46%). Among invasive-VPD, two clusters were found: the second with more frequent HER2/neu overexpression (67% vs. 0%) and nodal metastases (100% vs. 25%). Repeating the IHC panel on the correspondent MLS and RVS, it significantly changed, respectively, in 50% and 27%.

Conclusions

This study reveals the expression of PDL-1 and ER and confirms the expression of HER2/AR in VPD; new bases are provided to design multicenter clinical trials on personalized target therapies.

Keywords

Gynecological cancers Biostatistics Molecular targets Vulvar cancer Immunohistochemistry 

Notes

Author contributions

Study conception and design: GG, FI, MF, AF, GS, GFZ, GB. Acquisition of data: GM, GP, AS, MV, SMF, SB, SG, GA. Analysis and interpretation of data: GB, GG, FI, GM, GP, AS, MV, SMF, SB, GA. Drafting of manuscript: GG, FI, GM, GP, AS, MV, SMF, SB, GA. Critical revision: MF, AF, GS, GFZ, SG, GG, FI, GB. Final approval: GG, FI, GM, AS, MV, GB, GP, SMF, SG, SB, MF, AF, GS, GFZ, GA.

Funding

None.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

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

Authors and Affiliations

  • Giorgia Garganese
    • 1
    • 2
  • Frediano Inzani
    • 3
  • Giulia Mantovani
    • 4
  • Angela Santoro
    • 3
  • Michele Valente
    • 3
  • Gabriele Babini
    • 1
  • Giuliana Petruzzellis
    • 5
  • Simona Maria Fragomeni
    • 5
    Email author
  • Stefano Gentileschi
    • 6
    • 7
  • Sonia Bove
    • 2
  • Massimo Franchi
    • 8
  • Giuseppe Angelico
    • 3
  • Anna Fagotti
    • 5
    • 9
  • Giovanni Scambia
    • 5
    • 9
  • Gian Franco Zannoni
    • 3
    • 10
  1. 1.Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità PubblicaFondazione Policlinico Universitario A. Gemelli IRCCSRomeItaly
  2. 2.Mater Olbia Hospital, Gynecology and Breast Care CenterOlbiaItaly
  3. 3.Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Unità di Gineco-patologia e Patologia MammariaFondazione Policlinico Universitario A. Gemelli IRCCSRomeItaly
  4. 4.IRCCS Ospedale Sacro Cuore Don Calabria, Dipartimento di Ginecologia e Ostetricia, Ginecologia Oncologica e Chirurgia Pelvica Mini-InvasivaInternational School of Surgical AnatomyVeronaItaly
  5. 5.Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Unità di Ginecologia OncologicaFondazione Policlinico Universitario A. Gemelli IRCCSRomeItaly
  6. 6.Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Unità di Chirurgia PlasticaFondazione Policlinico Universitario A. Gemelli IRCCSRomeItaly
  7. 7.Istituto di Clinica ChirurgicaUniversità Cattolica del Sacro CuoreRomeItaly
  8. 8.Department of Gynecology and ObstetricsUniversità degli Studi di VeronaVeronaItaly
  9. 9.Istituto di Clinica Ostetrica e GinecologicaUniversità Cattolica del Sacro CuoreRomeItaly
  10. 10.Istituto di Anatomia PatologicaUniversità Cattolica del Sacro CuoreRomeItaly

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