The current series is characterized by primary CNS tumor-bearing patients whose ages were similar to those of patients in other studies [15, 16]. Meningiomas prevailed in association with female predominance . Regarding location, most meningiomas in our sample occurred at different locations as compared to most tumors described in the literature .
In our study, 28.6% of the sample presented positive IH to PRL. Unlike Abech and colleagues’ findings , PRL was positive in older patients in our series. In 1999, positive IH for PRL was described in a patient with gangliocytoma .
Hyperprolactinemia and presence of intracellular PRL and PRL-R have been detected by immunohistochemistry in different types of CNS tumors. Cicarelli and colleagues  found hyperprolactinemia and presence of PRL-R in 27.2% and 45.4% of meningiomas and 61.5% and 69.2% of schwannomas, without correlation of hyperprolactinemia with PRL-R. Leães and colleagues  identified hyperprolactinemia in 30.5%, presence of intracellular PRL in 21.9% and PRL-R in 39% of 82 cases, with positive correlation of serum PRL with presence of intracellular PRL. A recent study by Abech and colleagues  revealed presence of intracellular PRL in 45.6% of neuroepithelial tumors and meninges and elevated serum PRL in 33.9% of the cases. Therefore, our findings of positive intracellular PRL are similar to the those of the literature. The meaning of intracellular presence of PRL may vary according to the malignant potentials of the tumors, and there is no data in the current literature on the possible causes for the presence of positive PRL immunohistochemistry in different types of CNS tumors. However, in gliomas of different grades, Scott and colleagues  found a significant increase in the expression of Ki-67, Mcm-2 and cyclin A and B1 as tumor grade increased, and it is speculated that PRL, like the above-mentioned proteins, may be related to more aggressive tumors . Ducret and colleagues  demonstrated increased intracellular calcium in glioblastoma cells induced by the presence of PRL, increased thymidine incorporation, cell growth and half-life. Regarding meningiomas, Jimenez-Hakim and colleagues  demonstrated that PRL concentrations stimulated the growth of meningiomas significantly.
A single report utilizing conventional PCR detected PRL mRNA expression in the human hypothalamus, pituitary and cerebellum . In studies with rats, PRL mRNA was detected in various degrees in the hypothalamus, cerebellum, caudate, brain stem, amygdala, thalamus, hippocampus and cortex [24, 25]. In this study, no expression of PRL was identified in the pool of 9 samples of CNS peritumoral tissue (gray and white matter and meningothelial tissue) through quantitative real-time PCR. Real-time PCR is the most powerful tool for quantitative nucleic acids analysis. It is widely considered as the gold standard for nucleic acid quantification and has become the method of choice for the detection of mRNA because of its unparalleled amplification and precision capability [26–29]. Sample of prolactinoma was used as positive control, demonstrating that real-time PCR is able to identify PRL expression. It removes the possibility that the technique was not sensitive enough to detect PRL and to corroborate immunohistochemical findings. In general, polyclonal antibodies have high affinity and wide reactivity, becoming more sensible as compared with monoclonal antibodies because they are more likely to identify multiple epitopes of the target protein. However, their specificity is lower as compared to monoclonal antibodies, being more susceptible to cross-reactivity with other antigens . PCR methods generally have a higher sensitivity and specificity than immunohistochemical ones and agreement between results of immunohistochemistry and PCR methods can be low [31–33]. Real time -PCR is the most sensitive method for the detection and quantification of mRNA, especially for low abundance specimens, like RNAs, cells and tissues [27, 34]. Real time-PCR assays are 10.000 to 100.000-fold more sensitive than RNase protection assays, 1000-fold more sensitive than dot blot hybridization, detecting a single copy of a specific transcript and is a method with lower variation, usually between 0 and 5% for TaqMan probes [27–29, 34, 35]. The real time -PCR technique, specially with TaqMan probes, is the best option when analyzing gene with low expression level, from limited samples once high sensitivity and accuracy are needed [27, 36]. There is no data in the current literature about PRL gene expression by quantitative real-time PCR in normal samples of the CNS. To the best of our knowledge, there are no studies analyzing PRL gene expression in different types of CNS tumors either by conventional PCR or by quantitative real-time PCR. Therefore, the absence of PRL expression by quantitative real-time PCR in human samples of different types of CNS tumors, the main finding of this study, is an unprecedented one.
So far, the identification of positive PRL by immunohistochemistry suggested possible extrapituitary hormone production, but immunological methods do not allow to discriminate between locally produced PRL and PRL that is captured by dependent or independent mechanism of the PRL-R. The PRL-R is ubiquitously expressed and its isoforms vary across tissues. The long isoform is highly expressed in the choroid plexus, mammary gland, pancreas, adrenal, kidney and intestine. In the brain, with the exception of the choroid plexus, there is a low expression of PRL-R. PRL-R triggers intracellular signaling pathways, the best known of which being the Jak-Stat. In breast cancer cells, PRL activates Jak2, stimulates phosphorylation of Stat1, Stat3 and Stat5 and induces cell proliferation [37, 38]. In breast cancer cells and Nb2 cells, PRL stimulates ERK1/2 phosphorylation in the mitogen-activated protein (MAP) kinase pathway, which appears to mediate the effects of PRL on cell proliferation [39, 40]. The PRL-R facilitates the action of members of the Src kinase family, activating kinase B protein and the phosphatidylinositol 3-kinase (PI3 kinase) pathway . The interconnection between the different signaling pathways of PRL can increase the proliferation, survival, cell migration and invasion of breast cancer  and is responsible for mediating antiapoptotic and proliferative effects of PRL . The absence of PRL detection by quantitative real-time PCR does not favor the hypothesis of local production because, unlike IH, it is a method that analyses the mRNA of protein in order to identify local production of PRL. In a study by Abech and colleagues , 45.6% of cases presented positive IH to PRL and 30.6% of cases presented hyperprolactinemia. In addition, in a study carried out by Leães and colleagues , of the total number of patients with positive IH to intracellular PRL, 27.8% presented hyperprolactinemia, 38.9% were positive for PRL-R, and 44.4% had neither of the two variables. Although the available data do not allow us to define the origin of positive IH PRL in primary tumors of the CNS, they strongly suggest that it does not reflect local production. It is postulated that the presence of PRL in CNS is due to the transport of pituitary PRL from the blood by the choroid plexus, with subsequent distribution via cerebrospinal fluid and taking up by neurons and glial cells to exert modulatory functions. It is presumed that the PRL receptor or binding protein in the choroid plexus functions as a transporter, enabling circulating PRL to gain access to various brain regions [2, 44, 45].