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The vulvar immunohistochemical panel (VIP) project: molecular profiles of vulvar Paget's disease
Giorgia Garganese1,2, Frediano Inzani3, Giulia Mantovani4
1Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
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.