title: Transcriptional profiling of melanoma sentinel nodes identify patients with poor outcome and reveal an association of CD30(+) T lymphocytes with progression.
abstract: Sentinel lymph nodes set the stance of the immune system to a localized tumor and are often the first site to be colonized by neoplastic cells that metastasize. To investigate how the presence of neoplastic cells in sentinel lymph nodes may trigger pathways associated with metastatic progression, we analyzed the transcriptional profiles of archival sentinel node biopsy specimens obtained from melanoma patients. Biopsies from positive nodes were selected for comparable tumor infiltration, presence or absence of further regional node metastases, and relapse at 5-year follow-up. Unsupervised analysis of gene expression profiles revealed immune response to be a major gene ontogeny represented. Among genes upregulated in patients with progressing disease, the TNF receptor family member CD30/TNFRSF8 was confirmed in biopsy specimens from an independent group of patients. Immunohistochemical analysis revealed higher numbers of CD30(+) lymphocytes in nodes from progressing patients compared with nonprogressing patients. Phenotypic profiling demonstrated that CD30(+) lymphocytes comprised a broad population of suppressive or exhausted immune cells, such as CD4(+)Foxp3(+) or PD1(+) subpopulations and CD4(-)CD8(-) T cells. CD30(+) T lymphocytes were increased in peripheral blood lymphocytes of melanoma patients at advanced disease stages. Our findings reinforce the concept that sentinel nodes act as pivotal sites for determining progression patterns, revealing that the presence of CD30(+) lymphocytes at those sites associate positively with melanoma progression.
authors.affiliation: Authors' Affiliations: Immunotherapy Unit; Department of Pathology; Functional Genomics Unit; Immunobiology of Human Tumors Unit; Department of Medical Statistics and University of Milan, Medical Statistics Biometry and Bioinformatics Unit; Department of Surgery, Melanoma and Sarcoma Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan; Microscopy and Image Analysis, University of Milan Bicocca, Milan; Department of Immunohematology and Transfusion Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Vallacchi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Vergani
authors.forename: Chiara
authors.initials: C
authors.lastname: Camisaschi
authors.forename: Paola
authors.initials: P
authors.lastname: Deho
authors.forename: Antonello D
authors.initials: AD
authors.lastname: Cabras
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Sensi
authors.forename: Loris
authors.initials: L
authors.lastname: De Cecco
authors.forename: Niccolò
authors.initials: N
authors.lastname: Bassani
authors.forename: Federico
authors.initials: F
authors.lastname: Ambrogi
authors.forename: Antonino
authors.initials: A
authors.lastname: Carbone
authors.forename: Federica
authors.initials: F
authors.lastname: Crippa
authors.forename: Barbara
authors.initials: B
authors.lastname: Vergani
authors.forename: Paola
authors.initials: P
authors.lastname: Frati
authors.forename: Flavio
authors.initials: F
authors.lastname: Arienti
authors.forename: Roberto
authors.initials: R
authors.lastname: Patuzzo
authors.forename: Antonello
authors.initials: A
authors.lastname: Villa
authors.forename: Elia
authors.initials: E
authors.lastname: Biganzoli
authors.forename: Silvana
authors.initials: S
authors.lastname: Canevari
authors.forename: Mario
authors.initials: M
authors.lastname: Santinami
authors.forename: Chiara
authors.initials: C
authors.lastname: Castelli
authors.forename: Licia
authors.initials: L
authors.lastname: Rivoltini
authors.forename: Monica
authors.initials: M
authors.lastname: Rodolfo
mesh_terms: D019295:Computational Biology; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D017730:Ki-1 Antigen / Q000276:immunology*; D008545:Melanoma / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D021701:Sentinel Lymph Node Biopsy / Q000379:methods*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D059467:Transcriptome; D016896:Treatment Outcome
chemical_list: D017730:Ki-1 Antigen