Giorgia Garganese1,2, Frediano Inzani3, Giulia Mantovani4, Angela Santoro3, Michele Valente3, Gabriele Babini1, Giuliana Petruzzellis5, Simona Maria Fragomeni6, Stefano Gentileschi7,8, Sonia Bove2, Massimo Franchi9, Giuseppe Angelico3, Anna Fagotti5,10, Giovanni Scambia5,10, Gian Franco Zannoni3,11. 1. Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 2. Mater Olbia Hospital, Gynecology and Breast Care Center, Olbia, Italy. 3. Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Unità di Gineco-patologia e Patologia Mammaria, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 4. IRCCS Ospedale Sacro Cuore Don Calabria, Dipartimento di Ginecologia e Ostetricia, Ginecologia Oncologica e Chirurgia Pelvica Mini-Invasiva, International School of Surgical Anatomy, Verona, Negrar, Italy. 5. Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Unità di Ginecologia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, largo A. Gemelli 8, 00168, Rome, Italy. 6. Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Unità di Ginecologia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, largo A. Gemelli 8, 00168, Rome, Italy. simona.fragomeni@gmail.com. 7. Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Unità di Chirurgia Plastica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 8. Istituto di Clinica Chirurgica, Università Cattolica del Sacro Cuore, Rome, Italy. 9. Department of Gynecology and Obstetrics, Università degli Studi di Verona, Verona, Italy. 10. Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del Sacro Cuore, Rome, Italy. 11. Istituto di Anatomia Patologica, Università Cattolica del Sacro Cuore, Rome, Italy.
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.
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.
Entities:
Keywords:
Biostatistics; Gynecological cancers; Immunohistochemistry; Molecular targets; Vulvar cancer
Authors: Mario Preti; Elmar Joura; Pedro Vieira-Baptista; Marc Van Beurden; Federica Bevilacqua; Maaike C G Bleeker; Jacob Bornstein; Xavier Carcopino; Cyrus Chargari; Margaret E Cruickshank; Bilal Emre Erzeneoglu; Niccolò Gallio; Debra Heller; Vesna Kesic; Olaf Reich; Colleen K Stockdale; Bilal Esat Temiz; Linn Woelber; François Planchamp; Jana Zodzika; Denis Querleu; Murat Gultekin Journal: J Low Genit Tract Dis Date: 2022-06-21 Impact factor: 3.842
Authors: Zoran Gatalica; Semir Vranic; Božo Krušlin; Kelsey Poorman; Phillip Stafford; Denisa Kacerovska; Wijendra Senarathne; Elena Florento; Elma Contreras; Alexandra Leary; April Choi; Gino K In Journal: Cancer Med Date: 2020-01-03 Impact factor: 4.452