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.

Garganese, G., Inzani, F., Mantovani, G., Santoro, A., Valente, M., Babini, G., Petruzzellis, G., Fragomeni, S. M., Gentileschi, S., Bove, S., Franchi, M., Angelico, G., Fagotti, A., Scambia, G., Zannoni, G. F., The vulvar immunohistochemical panel (VIP) project: molecular profiles of vulvar Paget's disease, <<JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY>>, 2019; 145 (9): 2211-2225. [doi:10.1007/s00432-019-02975-3] [http://hdl.handle.net/10807/149034]

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

Garganese, Giorgia;Inzani, Frediano;Gentileschi, Stefano;Fagotti, Anna;Scambia, Giovanni;Zannoni, Gian Franco
2019

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.
Inglese
Garganese, G., Inzani, F., Mantovani, G., Santoro, A., Valente, M., Babini, G., Petruzzellis, G., Fragomeni, S. M., Gentileschi, S., Bove, S., Franchi, M., Angelico, G., Fagotti, A., Scambia, G., Zannoni, G. F., The vulvar immunohistochemical panel (VIP) project: molecular profiles of vulvar Paget's disease, <>, 2019; 145 (9): 2211-2225. [doi:10.1007/s00432-019-02975-3] [http://hdl.handle.net/10807/149034]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/149034
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