title: Galectin-3 is a marker of favorable prognosis and a biologically relevant molecule in neuroblastic tumors.
abstract: Childhood neuroblastic tumors are characterized by heterogeneous clinical courses, ranging from benign ganglioneuroma (GN) to highly lethal neuroblastoma (NB). Although a refined prognostic evaluation and risk stratification of each tumor patient is becoming increasingly essential to personalize treatment options, currently only few biomolecular markers (essentially MYCN amplification, chromosome 11q status and DNA ploidy) are validated for this purpose in neuroblastic tumors. Here we report that Galectin-3 (Gal-3), a β-galactoside-binding lectin involved in multiple biological functions that has already acquired diagnostic relevance in specific clinical settings, is variably expressed in most differentiated and less aggressive neuroblastic tumors, such as GN and ganglioneuroblastoma, as well as in a subset of NB cases. Gal-3 expression is associated with the INPC histopathological categorization (P<0.001) and Shimada favorable phenotype (P=0.001), but not with other prognostically relevant features. Importantly, Gal-3 expression was associated with a better 5-year overall survival (P=0.003), and with improved cumulative survival in patient subsets at worse prognosis, such as older age at diagnosis, advanced stages or NB histopathological classification. In vitro, Gal-3 expression and nuclear accumulation accompanied retinoic acid-induced cell differentiation in NB cell lines. Forced Gal-3 overexpression increased phenotypic differentiation and substrate adherence, while inhibiting proliferation. Altogether, these findings suggest that Gal-3 is a biologically relevant player for neuroblastic tumors, whose determination by conventional immunohistochemistry might be used for outcome assessment and patient's risk stratification in the clinical setting.
authors.affiliation: Department of Molecular Medicine, University La Sapienza, Rome, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Veschi
authors.affiliation: Department of Molecular Medicine, University La Sapienza, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Petroni
authors.affiliation: 1] Department of Pathology, St. Andrea Hospital, Rome, Italy [2] Pathology Research Laboratory, Cancer Center Karolinska (CCK), Karolinska Hospital, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Bartolazzi
authors.affiliation: Unit of Radiation Biology and Human Health, Italian National Agency for New Technologies, Energy and Sustainable Economic Development, Research Center Casaccia, Rome, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Altavista
authors.affiliation: 1] Department of Pediatrics and Infantile Neuropsychiatry, University La Sapienza, Rome, Italy [2] School of Reproductive and Developmental Medicine, Liverpool University, Liverpool, UK.
authors.forename: C
authors.initials: C
authors.lastname: Dominici
authors.affiliation: Department of Molecular Medicine, University La Sapienza, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Capalbo
authors.affiliation: Division of Pathology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Boldrini
authors.affiliation: Division of Oncology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Castellano
authors.affiliation: 1] Department of Pediatrics and Infantile Neuropsychiatry, University La Sapienza, Rome, Italy [2] School of Reproductive and Developmental Medicine, Liverpool University, Liverpool, UK.
authors.forename: H P
authors.initials: HP
authors.lastname: McDowell
authors.affiliation: Department of Oncology, Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
authors.forename: B
authors.initials: B
authors.lastname: Pizer
authors.affiliation: Department of Experimental Medicine, University La Sapienza, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Frati
authors.affiliation: Department of Molecular Medicine, University La Sapienza, Rome, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Screpanti
authors.affiliation: Department of Molecular Medicine, University La Sapienza, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Gulino
authors.affiliation: Department of Molecular Medicine, University La Sapienza, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Giannini
mesh_terms: D000293:Adolescent; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001798:Blood Proteins; D002448:Cell Adhesion; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D005260:Female; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D037161:Galectins; D018305:Ganglioneuroblastoma / Q000378:metabolism / Q000473:pathology; D005729:Ganglioneuroma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011237:Predictive Value of Tests; D012307:Risk Factors; D013997:Time Factors; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; D001798:Blood Proteins; D037502:Galectin 3; D037161:Galectins; C428445:LGALS3 protein, human