title: Different Growth Patterns of Canine Prostatic Carcinoma Suggests Different Models of Tumor-Initiating Cells.
abstract: Controversies remain regarding the cell type from which human prostate cancer originates, and many attempts have been made to identify the cellular origin of canine prostate cancer but without definitive proof. This study aims to evaluate the expression of luminal (androgen receptor [AR], cytokeratin [CK]8/18) and basal (CK14, CK5) cell markers in different histologic subtypes of canine prostatic carcinoma (PC) and to suggest the most likely tumor-initiating cells. Normal prostates (n = 8) were characterized by AR+CK8/18+ luminal cells and few CK5+ basal cells, while CK14 was absent. Similar pattern was observed in all 35 prostates with benign prostatic hyperplasia, except few scattered CK14+ basal cells in 13 samples (37.14%). AR was localized in the nucleus of both normal and hyperplastic cells. In 34 samples of PC, the following growth patterns were identified: cribriform (44.12%), solid (32.35%), small acinar/ductal (20.59%), and micropapillary (2.94%). Most PCs expressed AR and CK8/18, while CK5 and CK14 expression was observed in 25% and 20% of cases, respectively. AR revealed a variable intracellular distribution, both nuclear and cytoplasmic. Solid PC was characterized by an undifferentiated or aberrant phenotype with a reduced expression of AR and CK8/18, increased number of CK14+ cells, and 7 antigen expression patterns. This study demonstrated a predominance of differentiated luminal cell types in canine prostatic tumors, although the role of basal cells in prostate carcinogenesis should also be considered. Moreover, few scattered CK5+ cells in AR+CK8/18+ tumors identified the existence of intermediate cells, from which neoplastic transformation may alternatively commence.
authors.affiliation: School of Veterinary Science, The University of Queensland, Gatton Campus, Gatton, Queensland, Australia.
authors.forename: S H
authors.initials: SH
authors.lastname: Akter
authors.affiliation: School of Veterinary Science, The University of Queensland, Gatton Campus, Gatton, Queensland, Australia.
authors.forename: F Z X
authors.initials: FZ
authors.lastname: Lean
authors.affiliation: School of Veterinary Science, The University of Queensland, Gatton Campus, Gatton, Queensland, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Veterinary Science and Public Health, Universita' degli Studi di Milano, Milan, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Grieco
authors.affiliation: School of Veterinary Science, The University of Queensland, Gatton Campus, Gatton, Queensland, Australia c.palmieri@uq.edu.au.
authors.forename: C
authors.initials: C
authors.lastname: Palmieri
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000473:pathology / Q000662:veterinary*; D002454:Cell Differentiation; D004285:Dogs; D007150:Immunohistochemistry / Q000662:veterinary; D007633:Keratins / Q000032:analysis; D008297:Male; D014411:Neoplastic Stem Cells / Q000473:pathology; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000473:pathology / Q000662:veterinary*; D011944:Receptors, Androgen / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D011944:Receptors, Androgen; D007633:Keratins
keywords: androgen receptor; cell of origin; cytokeratins; dog; growth patterns; immunohistochemistry; prostate carcinoma; tumor infiltrating