[Non-functioning pituitary adenomas: clinical features and immunohistochemistry].
Clinically non-functioning pituitary adenomas do not produce clinical signs of hormonal hypersecretion. Therefore, signs and symptoms will depend on the mass effect of these adenomas over the central nervous system. Their etiopathogeny is complex and their development is probably influenced by several factors, such as hypothalamic hormones (GHRH), growth factors (FGF), proliferation factors (PCNA, and KI-67), protein P53 and the proto-oncogene c-erb-B2.


OBJECTIVE
1) Determining the clinical features of a population of 117 patients treated for clinically non-functioning pituitary adenoma (age, sex, tumor size, number of surgical procedures, development of hormonal deficiency and hyperprolactinemia). 2) Identifying, after the patients had been clinically characterized, those with clinically non-functioning adenomas with positive immunohistochemistry for hypophyseal hormones (PRL, LH, FSH, GH, TSH and ACTH). 3) Determining if the immunohistochemistry of this population was positive for the cellular proliferation factor Ki-67, protein P53 and protein C-erb-B2 and establishing a correlation with tumor size and tumor invasiveness. This will help in the evaluation of the prognostic value of these proliferation factors. 4) Confronting the results of immunohistochemistry using a standard block with the results of immunohistochemistry using a tissue micro-array.


METHODS
Study of the clinical features of 117 patients with clinically non-functioning pituitary adenoma (age, sex, tumor size, number of surgical procedures, development of hormonal deficiency and hyperprolactinemia). Immunohistochemical study (H&E) of 39 patients for hypophyseal hormones, protein P53, protein C-erb-B2, Ki-67 to establish their correlation to tumor growth. The next step was a tissue micro-array of the 39 previously studied cases, using immunohistochemistry for hypophyseal hormones, protein P 53, protein C-erb-B2, Ki-67 to establish their correlation to tumor growth.


RESULTS
There was no statistically significant difference between males and females with regards to age, tumor size and number of surgical procedures (p=0.279, p=813, p=139 respectively). There is a statistically significant correlation between the size of the tumor, the number of surgical procedures and hormonal deficiency (p=0.032, p=0.223 respectively). There was no statistically significant correlation between a positive immunohistochemistry for protein P53, protein C-erb-B2, Ki-67 and tumor size (r=0.182, p=0.396; r=-0.181, p=0.397; r=0.272, p=0.199, respectively). The tissue micro-array also did not demonstrate a correlation between positive immunohistochemistry for Ki-67 and C-erb-B2 and tumor size, but it showed a statistically significant correlation between a positive immunohistochemistry for p53 and tumor size (r=-0.696; p=001).


CONCLUSIONS
The biological behavior of the clinically non-functioning adenoma is similar for both sexes. The larger the tumor the greater the number of surgical procedures needed. Hormonal deficiency also becomes more significant as the size of the tumor increases. This paper suggests that a positive immunohistochemistry for p53 is negatively correlated to tumor size, thus demonstrating that it has a predictor value. However, a positive immunohistochemistry for Ki-67 and protein C-erb-B2 does not seem to be a prognostic factor for clinically non-functioning pituitary adenomas, as is the case with other neoplasias.
Ferreira
Jane Eyre Alves
JE
Departamento de Neuroendocrinologia, Universidade Nacional de Brasilia, DF, Brasil. janeyreaf@yahoo.com.br
de Mello
Paulo Andrade
PA
de Magalhães
Albino Verçosa
AV
Botelho
Carlos Henrique Aguiar
CH
Naves
Luciana Ansaneli
LA
Nosé
Vania
V
Schmitt
Fernando
F
D000236:Adenoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000097:blood / Q000378:metabolism; D008297:Male; D010907:Pituitary Hormones / Q000097:blood / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood / Q000378:metabolism; D012720:Severity of Illness Index; D016159:Tumor Suppressor Protein p53 / Q000097:blood / Q000378:metabolism
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D010907:Pituitary Hormones; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C000715470:MAS1 protein, human