Determination of cell proliferation using Mcm2 antigen and evaluation of apoptosis and TGF-beta1 expression in GH-secreting or clinically nonfunctioning pituitary adenomas.
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.
Dallago
Cristina Micheletto
CM
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.
Barbosa-Coutinho
Ligia Maria
LM
Ferreira
Nelson Pires
NP
Meurer
Rosalva
R
Pereira-Lima
Julia Fernanda Semmelmann
JF
Oliveira
Miriam da Costa
Mda C
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
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