title: Nuclear pleomorphism: role in grading and prognosis of canine mammary carcinomas.
abstract: Canine mammary tumours are highly heterogeneous in morphology and behaviour and successful clinical management requires robust prognostic factors. Histological grade, determined by the Nottingham nuclear pleomorphism scoring method, has been considered one of these factors. Despite the adoption of this method, it is unknown whether inter-observer agreement exists regarding the assessment of its parameters in canine mammary carcinomas (CMC). In this study, the agreement between two observers in scoring nuclear pleomorphism using the Nottingham method was evaluated in 89 cases of CMC. Histological evidence of vascular invasion and/or lymph node metastases (both early signs of tumour aggressiveness) was recorded. For 48 animals, two years of follow-up data were available. Nuclear pleomorphism was quantitatively assessed using a stereological method that allowed for an unbiased estimation of nuclear size and its variability by determining the volume-weighted mean nuclear volume (v¯v). Differences between the v¯v estimations and nuclear pleomorphism scores were evaluated. Additionally, the prognostic significance of clinicopathological features including nuclear score and v¯v was evaluated. A poor agreement between the two observers was obtained (κ value 0.46). Tumours scored as 1 and 2 presented similar v¯v values and only tumours that scored 3 presented significantly higher estimates. The v¯v value was not associated with vascular invasion and/or lymph node metastases, but was higher in tumours that progressed during follow-up. In multivariable analysis, only tumour size was an independent factor regarding evidence of aggressiveness and an optimal cut-off of 2.9 cm was defined.
authors.affiliation: Laboratory of Histology and Embryology, Department of Microscopy, Instituto Ciências Biomédicas Abel Salazar, ICBAS - UPorto, University of Porto, Portugal. Electronic address: mssantos@icbas.up.pt.
authors.forename: Marta
authors.initials: M
authors.lastname: Santos
authors.affiliation: Epidemiology Research Unit, Future Farming Systems, Scotland's Rural College (SRUC), UK.
authors.forename: Carla
authors.initials: C
authors.lastname: Correia-Gomes
authors.affiliation: Faculty of Veterinary Medicine - Lusófona University of Humanities and Technologies (FMV-ULHT), Lisboa, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Santos
authors.affiliation: Department of Veterinary Clinics, ICBAS - UPorto, Portugal; Animal Science and Study Central (CECA), Food and Agrarian Sciences and Technologies Institute (ICETA), UPorto, Portugal.
authors.forename: Augusto
authors.initials: A
authors.lastname: de Matos
authors.affiliation: Laboratory of Histology and Embryology, Department of Microscopy, Instituto Ciências Biomédicas Abel Salazar, ICBAS - UPorto, University of Porto, Portugal; CIIMAR/CIMAR LA, Laboratory of Cellular, Molecular and Analytical studies, Interdisciplinary Centre for Marine and Environmental Research, UPorto, Portugal.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Rocha
authors.affiliation: Department of Pathology and Molecular Immunology, ICBAS - UPorto, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopes
authors.affiliation: Department of Pathology and Molecular Immunology, ICBAS - UPorto, Portugal.
authors.forename: Patrícia Dias
authors.initials: PD
authors.lastname: Pereira
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000473:pathology / Q000662:veterinary*; D053145:Cell Nucleus Size; D004283:Dog Diseases / Q000473:pathology*; D004285:Dogs; D005260:Female; D005500:Follow-Up Studies; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008321:Mammary Glands, Animal / Q000473:pathology*; D015674:Mammary Neoplasms, Animal / Q000473:pathology*; D015999:Multivariate Analysis; D060787:Neoplasm Grading / Q000662:veterinary; D015588:Observer Variation; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies
keywords: Canine; Histological grade; Mammary tumours; Nuclear volume; Prognosis; Stereology