title: Determination of cell proliferation using Mcm2 antigen and evaluation of apoptosis and TGF-beta1 expression in GH-secreting or clinically nonfunctioning pituitary adenomas.
abstract: Pituitary adenomas (PA) occasionally show aggressive behavior, with invasion of the surrounding tissues. The identification of markers able to recognize aggressive PA in early stages remains a challenge. We aimed to determine the expression of a new cell proliferation marker, Mcm2, and the presence of apoptosis in PA, and to evaluate the association of clinicopathological features with the apoptotic and proliferative indices. Additionally, the TGF-beta1 expression, an inducer of apoptosis, was determined. The proliferative index was determined in GH-secreting or clinically nonfunctioning PA using immunohistochemical (IH) methods for Mcm2 and Ki-67 antigens. The apoptosis was assessed by the TUNEL method and the TGF-beta1 expression by IH. A significant positive correlation was found between log Mcm2 index and log Ki-67 index (p < 0.001). Mcm2 and Ki-67 detected a similar number of proliferating cells. Mcm2 index showed a significant association with tumor extension (p = 0.02), but not with tumor invasion. Apoptosis was detected in 17% of the adenomas, with a maximum apoptotic index of 0.77%. Immunoreactivity to TGF-beta1 was observed in 77% of the adenomas, showing an association with tumor extension. We concluded that, in this sample, Mcm2 was similar to Ki-67 in the identification of the proliferating cells and that apoptosis was rare.
authors.affiliation: Neuroendocrinology Center, Complexo Hospitalar Santa Casa, Universidade Federal de Ciências da Saúde de Porto Alegre (UFSCPA), Rua Dona Mimi Moro, 40, 90480-050, Porto Alegre, RS, Brazil.
authors.forename: Cristina Micheletto
authors.initials: CM
authors.lastname: Dallago
authors.forename: Ligia Maria
authors.initials: LM
authors.lastname: Barbosa-Coutinho
authors.forename: Nelson Pires
authors.initials: NP
authors.lastname: Ferreira
authors.forename: Rosalva
authors.initials: R
authors.lastname: Meurer
authors.forename: Julia Fernanda Semmelmann
authors.initials: JF
authors.lastname: Pereira-Lima
authors.forename: Miriam da Costa
authors.initials: Mda C
authors.lastname: Oliveira
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D048708:Cell Growth Processes / Q000502:physiology; D005260:Female; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D064111:Minichromosome Maintenance Complex Component 2; D009687:Nuclear Proteins / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D018709:Statistics, Nonparametric; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D053773:Transforming Growth Factor beta1; D019382:Human Growth Hormone; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2