PTTG overexpression in non-functioning pituitary adenomas: Correlation with invasiveness, female gender and younger age.

BACKGROUND: Non-functioning pituitary adenomas (NFPA) are prevalent pituitary neoplasms. Because they do not present with hormonal hypersecretion, there is no marker that indicates regrowth or recurrence, as in other adenomas. OBJECTIVES: Evaluate the immunohistochemical expression of PTTG, CD105 and Ki-67 and their relationships with age, gender, invasiveness, hormonal expression and regrowth or recurrence in the follow-up of NFPA operated and not submitted to radiotherapy. METHODS: Included 56 patients submitted to transsphenoidal surgery. Clinical data were obtained from medical records. The invasion degree was obtained by Hardy's classification. RESULTS: Mean age 55 ±â€¯13.6 years, 62.5% men and 68% invasive. Lesion persistence was present in 62.2% and regrowth in 35.7%. The recurrence-free survival rate was 94.5%, 75.4% and 69.1% (1, 2 and 3 years). No patient presented recurrence. The PTTG was positive in 55.3%, with statistically significant relationship with invasiveness, age and female gender, without relation to regrowth. The microvascular density showed statistically significant relationship with male gender, negative correlation with PTTG (r = -0.434, p = 0.001), and no relation with invasiveness and regrowth. The Ki-67 showed statistically significant relationship with age, tendency towards regrowth (p = 0.054) and, with no relation to invasiveness. CONCLUSIONS: It is suggested that PTTG can be used as a prognostic marker in NFPA.

Gene and protein expression of E-cadherin and NCAM markers in non-functioning pituitary adenomas.

Non-functioning pituitary adenomas (NFPA) are classified as benign tumors of slow growth, but 40% of them present local invasion, a characteristic of behavior still unpredictable with the use of current tumor markers. This work aims to evaluate the tissue markers E-cadherin and NCAM, which act on cell adhesion, in tumor tissue samples of NFPA and its relationship with the degree of local invasiveness. Gene expression of E-cadherin (CDH1) and NCAM (NCAM1) was assessed by real-time PCR and tissue expression by immunohistochemistry. Fifty-three patients with macroadenomas were submitted to transsphenoidal surgery, presented grade II invasive adenomas in 16 cases (30.2%), grade III in 7 (13.2%) and grade IV in 30 (56.6%). In the immunohistochemistry, one case was negative for E-cadherin, 7 showed weak immunostaining, 17 moderate and 28 strong, whereas for NCAM, 5 showed negative, 28 weakly, 14 moderate and 6 strong. Regarding gene expression, 43.3% showed expression for CDH1 (mean of 2.12) and 50% for NCAM1 (mean of 1.86). There was no significant correlation between the immunohistochemical expression of the markers, as well as the gene expression, the degree of invasiveness and clinical data. The results suggest that E-cadherin and NCAM markers are not directly related to the invasiveness in NFPA.

Decreased TAp63 and ΔNp63 mRNA Levels in Most Human Pituitary Adenomas Are Correlated with Notch3/Jagged1 Relative Expression.

Despite recent advances in molecular genetics, the pituitary adenoma initiation, development, progress, and the molecular basis of their unique features are still poorly understood. In this sense, it is proposed that stem cell could be involved in pituitary adenoma tumorigenesis. It is suggested that TP63 has important functions in stem cells, and it may have interplay of TP63 and Notch and its ligand Jagged in this process. This study aimed to evaluate the distinct expression of TP63 isoforms (TAp63 and ΔNp63), as well as its correlation with Notch3 receptor and its ligand Jagged1 in human pituitary adenomas at the messenger RNA (mRNA) level. We included 77 pituitary adenoma tumor samples from patients who underwent surgical resection. The expression levels of TP63 isoforms (TAp63 and ΔNp63) and Notch3 and its ligand Jagged1 were evaluated by qRT-PCR using isoform-specific primers. We also evaluated proliferation index immunohistochemically using KI-67 antibody. The expression levels were associated with clinical outcomes, as age, gender, tumor size, and tumor subtype. In summary, we found that mRNA expression of both TP63 isoforms decreased in pituitary adenomas compared with normal pituitary control. On the other hand, there was an increase of relative Notch3 and Jagged1 mRNA expression in the majority of examined samples. The mRNA expression of three genes evaluated was correlated and statistically significantly. There was no significant association between gene expression and the analyzed clinical data. The current study has provided the first time evidence that Tap63 and ΔNp63 isoforms are underexpressed in most pituitary adenomas. These results are correlated with Notch3 and its ligand Jagged1 overexpression, corroborating previous studies pointing its antagonistic interactions.

Population Genetics of Jaguars (Panthera onca) in the Brazilian Pantanal: Molecular Evidence for Demographic Connectivity on a Regional Scale.

Habitat loss and fragmentation are important threats to carnivores worldwide, and can be especially intense for large predators. Jaguars have already been extirpated from over half of their original area of distribution, and few regions still maintain large populations. For these, detailed understanding is crucial for setting appropriate recovery targets in impacted areas. The Pantanal is among the best examples of a region with a large jaguar population in a healthy environment. Here, we analyzed 12 microsatellite loci to characterize genetic diversity and population structure of 52 jaguars sampled in 4 localities of the southern Pantanal, and compared them with prior studies of heavily fragmented populations of the Atlantic Forest. Although we observed some internal structure among the Pantanal localities, our results indicated that this area comprises a single population with high genetic variability. Moreover, our comparative analyses supported the hypothesis that the strong population structure observed in the Atlantic Forest derives from recent, anthropogenic fragmentation. We also observed significant but low levels of genetic differentiation between the Pantanal and Atlantic Forest populations, indicating recent connectivity between jaguars occurring in these biomes. Evidence for admixture between the Pantanal and a population on the western boundary of the Atlantic Forest corroborates the transitional nature of the latter area, where the jaguar population has already been extirpated. Our results can be used to understand jaguar population dynamics in a region that is less disturbed than the Atlantic forest, and to support the design of conservation strategies that maintain and restore natural connectivity among currently isolated areas.

Expression of somatostatin receptors (SSTR1-SSTR5) in meningiomas and its clinicopathological significance.

Meningiomas are benign brain tumors that are usually to recur. Studies have shown in vitro and in vivo that meningiomas, regardless of histology and classification, express somatostatin receptors (SSTRs). We investigated the immunohistochemical expression of five SSTR subtypes (SSTR1-SSTR5) in tumor tissue sections from 60 patients with diagnosis of meningioma who underwent surgical resection and relating it to patient age and sex, tumor histology, location, regrowth/recurrence and follow-up. Mean (SD) patients age was 53.18 (12.6) years and 44 were women (73.3%). According to the WHO histological grading criteria, 47 (78.3%) meningiomas were grade I, 11 (18.3%) were grade II, and 2 (3.3%) were grade III. All five SSTRs were expressed in our sample, at frequencies ranging from 61.6 to 100%, with a predominance of SSTR2. SSTR5 was more frequently expressed in tumors benign than in tumors malignant (P<0.013). Recurrence-free survival rate at 2 years was 75.2%. There were no significant differences in SSTR expression regarding age, sex, tumor location and regrowth/recurrence. SSTR expression was detected at a significant frequency in this series. SSTR5 showed higher expression in tumors benign supporting the use of these SSTRs in diagnostic of meningiomas and their influence in process of tumorigenesis in meningiomas recurrence.

Development and testing of an optimized method for DNA-based identification of jaguar (Panthera onca) and puma (Puma concolor) faecal samples for use in ecological and genetic studies.

The elusive nature and endangered status of most carnivore species imply that efficient approaches for their non-invasive sampling are required to allow for genetic and ecological studies. Faecal samples are a major potential source of information, and reliable approaches are needed to foster their application in this field, particularly in areas where few studies have been conducted. A major obstacle to the reliable use of faecal samples is their uncertain species-level identification in the field, an issue that can be addressed with DNA-based assays. In this study we describe a sequence-based approach that efficiently distinguishes jaguar versus puma scats, and that presents several desirable properties: (1) considerably high amplification and sequencing rates; (2) multiple diagnostic sites reliably differentiating the two focal species; (3) high information content that allows for future application in other carnivores; (4) no evidence of amplification of prey DNA; and (5) no evidence of amplification of a nuclear mitochondrial DNA insertion known to occur in the jaguar. We demonstrate the reliability and usefulness of this approach by evaluating 55 field-collected samples from four locations in the highly fragmented Atlantic Forest biome of Brazil and Argentina, and document the presence of one or both of these endangered felids in each of these areas.