title: Programmed Death Ligand 1 (PD-L1) Tumor Expression Is Associated with a Better Prognosis and Diabetic Disease in Triple Negative Breast Cancer Patients.
abstract: Triple Negative Breast Cancers (TNBC) subtype is an aggressive disease with poor clinical outcome. The only treatment available is surgery followed by chemotherapy or radiotherapy. Programmed death-ligand 1 (PD-L1) is a trans-membrane protein expressed on a wide variety of cells including immune cells, epithelial and vascular endothelial cells. Recently, PD-1/PD-L1 pathway signaling was described as an adaptive immune resistance mechanism enacted by the tumor cells to evade the immune response. Its presence on tumor cell membranes, acquired for this reason, through time, is an important prognostic value. However, data available in the literature about PD-L1 immunohistochemical expression in breast cancer are often discordant and not uniform, probably for the use of different antibodies clones and the high molecular heterogeneity of the different tumor types. The absence of target therapies, in particular for TNBC, has shifted the clinical attention mainly on the role of PD-L1 in this subtype of breast cancer. In this study, we evaluated tumor and TIL (tumor infiltrating lymphocytes) PDL-1 expression in a series of TNBC, included in Tissue Micro Arrays (TMAs), to define its real prognostic value, optimizing immunohistochemistry method with an "approved for diagnostic assay" antibody. PD-L1 expression directly correlated with proliferation index (Ki-67), glycemia, the presence of diabetes and indirectly with menopausal status, presence of lymph node metastasis and relapse. The analysis of Kaplan-Meier showed that an increased PD-L1 expression was strongly associated with better disease-free survival (DFS) but not correlated with overall survival (OS). Our data confirmed that PD-L1 could be an important marker for prognostic stratification and for planning immune checkpoint inhibitors therapies in patients with TNBC.
authors.affiliation: Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. g.botti@istitutotumori.na.it.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
authors.affiliation: Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. francescacollina84@gmail.com.
authors.forename: Francesca
authors.initials: F
authors.lastname: Collina
authors.affiliation: Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. giosco80@gmail.com.
authors.forename: Giosuè
authors.initials: G
authors.lastname: Scognamiglio
authors.affiliation: Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. federica.rao@gmail.com.
authors.forename: Federica
authors.initials: F
authors.lastname: Rao
authors.affiliation: Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. valent.peluso@gmail.com.
authors.forename: Valentina
authors.initials: V
authors.lastname: Peluso
authors.affiliation: Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. r.dececio@istitutotumori.na.it.
authors.forename: Rossella
authors.initials: R
authors.lastname: De Cecio
authors.affiliation: Department of Breast Surgery and Cancer Prevention, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. m.piezzo@breastunit.org.
authors.forename: Michela
authors.initials: M
authors.lastname: Piezzo
authors.affiliation: Department of Breast Surgery and Cancer Prevention, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. g.landi@istitutotumori.na.it.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Landi
authors.affiliation: Department of Breast Surgery and Cancer Prevention, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. m.delaurentiis@istitutotumori.na.it.
authors.forename: Michelino
authors.initials: M
authors.lastname: De Laurentiis
authors.affiliation: Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. m.cantile@istitutotumori.na.it.
authors.forename: Monica
authors.initials: M
authors.lastname: Cantile
authors.affiliation: Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. mauriziodibonito@libero.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Di Bonito
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor; D003920:Diabetes Mellitus / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D012307:Risk Factors; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen
keywords: PD-L1; TNBC; diabetes