title: Prognostic factors in MNU and DMBA-induced mammary tumors in female rats.
abstract: Chemically-induced mammary tumors in rats by the carcinogens 1-methyl-1-nitrosourea- (MNU) and 7,12-dimethylbenz[a]anthracene (DMBA) are the most widely used models for studies related with human breast cancer. This study aimed to evaluate the immunoexpression of the prognostic factors estrogen receptor α (ERα), progesterone receptor (PR) and Ki-67, in MNU and DMBA-induced rat mammary tumors, in order to know the model that best suits to woman breast cancer. Twenty-eight MNU-induced and 16 DMBA-induced mammary tumors in virgin female Sprague-Dawley rats were analyzed. The expression of the prognostic markers ERα, PR and Ki-67 proliferation index (Ki-67 PI) was assessed by immunohistochemistry. Mitotic activity index (MAI) was also evaluated. More than one histological pattern was identified in each mammary tumor. Carcinomas constituted the lesions most frequently induced by both carcinogens: 33 MNU-induced carcinomas and 23 DMBA-induced carcinomas. All MNU and DMBA-induced mammary carcinomas were ER+/PR+, with a higher expression of ERα when compared with PR. Tumors' weight, the expression of ERα, PR, Ki-67 PI and MAI were higher in MNU-induced mammary carcinomas when compared with the DMBA-induced ones. Statistically significant differences between groups were observed for ERα, PR and MAI (p<0.05). The higher KI-67 PI and MAI in MNU-induced mammary carcinomas are suggestive of a higher aggressiveness of these carcinomas when compared with the DMBA-induced ones, and consequently a worse response to the therapy and a worse prognosis. In this way, the use of the rat model of MNU-induced mammary tumors is advised in experimental protocols aiming to study more aggressive mammary tumors within the group of double-positive mammary tumors (ER+/PR+).
authors.affiliation: Área de Patología, Decanato de Ciencias Veterinarias, Universidad Centroccidental "Lisandro Alvarado", UCLA, Lara, Venezuela; Department of Veterinary Sciences, School of Agrarian and Veterinary Sciences, University of Trás-os-Montes and Alto Douro, UTAD, Vila Real, Portugal; Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), UTAD, Real, Portugal.
authors.forename: Antonieta
authors.initials: A
authors.lastname: Alvarado
authors.affiliation: Departamento de Patologia Experimental, Faculdade de Medicina da Universidade de Coimbra, Portugal; Escola Universitária Vasco da Gama, Coimbra, Portugal.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Lopes
authors.affiliation: Department of Veterinary Sciences, School of Agrarian and Veterinary Sciences, University of Trás-os-Montes and Alto Douro, UTAD, Vila Real, Portugal; Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), UTAD, Real, Portugal; Organic Chemistry of Natural Products and Foodstuffs (QOPNA), Mass Spectrometry Center, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Faustino-Rocha
authors.affiliation: Departamento de Patologia Experimental, Faculdade de Medicina da Universidade de Coimbra, Portugal.
authors.forename: António M S
authors.initials: AMS
authors.lastname: Cabrita
authors.affiliation: Organic Chemistry of Natural Products and Foodstuffs (QOPNA), Mass Spectrometry Center, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Ferreira
authors.affiliation: Department of Veterinary Sciences, School of Agrarian and Veterinary Sciences, University of Trás-os-Montes and Alto Douro, UTAD, Vila Real, Portugal; Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), UTAD, Real, Portugal. Electronic address: pamo@utad.pt.
authors.forename: Paula A
authors.initials: PA
authors.lastname: Oliveira
authors.affiliation: Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), UTAD, Real, Portugal; Department of Zootechnics, School of Agrarian and Veterinary Sciences, UTAD, Vila Real, Portugal.
authors.forename: Bruno
authors.initials: B
authors.lastname: Colaço
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000009:adverse effects; D000818:Animals; D001943:Breast Neoplasms / Q000139:chemically induced / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D002273:Carcinogens; D002277:Carcinoma / Q000139:chemically induced / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D008770:Methylnitrosourea / Q000009:adverse effects; D011379:Prognosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011980:Receptors, Progesterone / Q000378:metabolism*
chemical_list: D002273:Carcinogens; D047628:Estrogen Receptor alpha; D019394:Ki-67 Antigen; D011980:Receptors, Progesterone; D015127:9,10-Dimethyl-1,2-benzanthracene; D008770:Methylnitrosourea
keywords: Chemical carcinogen; Estrogen receptor; Ki-67; Mammary cancer; Progesterone receptor; Sprague-Dawley