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.

Usefulness of clinical, ultrasonographic, hysteroscopic, and immunohistochemical parameters in differentiating endometrial polyps from endometrial cancer.

STUDY OBJECTIVE: To evaluate the usefulness of clinical, ultrasonographic, hysteroscopic, and immunohistochemical parameters in differentiating endometrial polyps from endometrial cancer. DESIGN: Cross-sectional study (Canadian Task Force classification II-2). SETTING: Tertiary public hospital, university teaching center. PATIENTS: Eighty-two women who underwent hysteroscopic polypectomy and 20 women who underwent surgery to treat endometrial cancer. INTERVENTIONS: Analysis of medical records and immunohistochemical assessment of estrogen receptors, progesterone receptors, and endothelial markers CD34 and CD105. MEASUREMENTS AND MAIN RESULTS: Among women with endometrial cancer and endometrial polyps, respectively, mean age was 63 and 57 years (p = .01), 89% and 67% were postmenopausal (p < .05), and 85% and 30.5% had postmenopausal bleeding (p < .01). No sonographic parameter enabled differentiation of endometrial polyp from cancer. Of patients with endometrial cancer, 72% exhibited signs suggestive of hyperplasia, and endometrial polyps were diagnosed during hysteroscopy. Estrogen receptors (≥ 2 vs ≥ 1; p < .001) and progesterone receptors (≥ 3 vs ≥ 2; p = .07) were greater in endometrial polyps. There was no significant difference in microvessel density (p > .05). CONCLUSIONS: Ultrasonographic parameters and endothelial markers did not enable differentiation of polyps from endometrial neoplasia. Postmenopausal bleeding and endometrial hypervascularization along with vascular atypia at diagnostic hysteroscopy showed a greater association with endometrial cancer.

Microvascular density and immunohistochemical expression of VEGF, VEGFR-1 and VEGFR-2 in benign prostatic hyperplasia, high-grade prostate intraepithelial neoplasia and prostate cancer.

INTRODUCTION: The aim of our study was to determine and compare angiogenesis in benign prostatic hyperplasia (BPH), high-grade prostate intraepithelial neoplasia (HGPIN) and prostate cancer (Pca). Moreover, we evaluated its role as a prognostic factor for Pca. MATERIAL AND METHODS: We examined 39, 12 and 51 samples of BPH, HGPIN and Pca, respectively. Immunohistochemical methods were applied in order to evaluate the expression of VEGF and its receptors (VEGFR-1, VEGFR-2), while microvascular density (MVD) was determined using CD105. In Pca samples, we recorded stage, differentiation, perineural invasion, adjuvant radiotherapy and their correlation with angiogenesis. RESULTS: 225 The expression of VEGF, VEGFR-1 and VEGFR-2 was significantly higher in Pca than compared to BPH (p <0.001, p <0.001 and p <0.001, respectively) and HGPIN (p <0.001, p <0.001 and p = 0.04, respectively), while there was no difference between BPH and HGPIN. MVD was higher in Pca compared to BPH (p <0.001) and HGPIN (p <0.01), while there was no difference between BPH and HGPIN. VEGF expression and MVD were significantly greater in Pca samples with poor differentiation (p = 0.044 and p = 0.038, respectively) and perineural invasion (p <0.001 and p = 0.019, respectively), while overexpression of VEGF was associated with advanced pathological stage (p = 0.047). CONCLUSIONS: Angiogenesis is more prominent in Pca than in BPH and HGPIN, while there is no difference between BPH and HGPIN. Pharmaceutical inhibition of angiogenesis could be a valuable therapeutic option for Pca in the near future.

Descrição da frequência de variantes genéticas no gene da endoglina em uma população do Nordeste do Brasil / Description of the frequency of genetic variants in the endoglin gene in a population of Northeast Brazil

Introdução: a endoglina (ENG, CD105) é um co-receptor da família transforming growth factor-beta e participa da regulação de processos celulares como proliferação, diferenciação, migração e apoptose. ENG é mais conhecida por sua expressão em células endoteliais, desempenhando papel importante na angiogênese e vasculogênese, porém sua expressão já foi associada a diferentes desfechos patogênicos, inclusive devido a mutações no gene ENG. Objetivos: descrever a frequência de variantes genéticas no gene ENG, comparar com populações ancestrais e analisar as variantes genéticas que possam estar envolvidas em processos patogênicos em outras populações. Metodologia: foi utilizado o banco de dados do programa SCAALA (Social Change Asthma and Allergy in Latin America) para a população do estudo, sendo genotipado 1309 indivíduos usando o chip Illumina 2.5 Human Omni Bead e feitas análises in silico utilizando plataformas on-line. Resultados: as variantes genéticas rs10987746, rs10121110, rs11792480 e rs16930129 apresentaram frequência de menor alelo entre 16 a 48% na população estudada, as quais foram mais reiteradamente próximas do padrão africano que do europeu. Os SNVs foram relacionados aos mecanismos regulatórios genéticos conhecidos, pressupondo que essas variantes não estejam envolvidas diretamente em processos funcionais. Conclusão: são necessárias maiores investigações referentes aos mecanismos funcionais deste gene, visto que a endoglina participa de uma gama de processos celulares importantes e mais esforços devem ser feitos para estudos genéticos na população brasileira, considerando a mistura de populações.

Introduction: the endoglin (ENG, CD105) is a coreceptor of the family transforming growth factor-beta and participates in the regulation of cellular processes such as proliferation, differentiation, migration and apoptosis. ENG She is best known for your expression in endothelial cells, playing an important role in angiogenesis and vasculogenesis, but its expression has already been associated with different pathogenic outcomes, including due to mutations in the ENG gene. Objectives: describe the frequency of genetic variants in the ENG gene in the population of northeastern Brazil, compare with ancestral populations and analyze genetic variants that may be involved in pathogenic processes in other populations. Methodology: we used the SCAALA program database (Social Change Asthma and Allergy in Latin America) for the population of the study, and the DNA of 1309 individuals were genotyped using the Illumina chip 2.5 Human Omni Bead and made in silico analysis. Results: the SNVs rs10987746, rs10121110, rs11792480 and rs16930129 presented lower allele frequency between 16 to 48% in the population studied, which were more consistently next African European standard. The SNVs were related to known genetic regulatory mechanisms assuming that these variants are not directly involved in functional processes. Conclusion: further investigation regarding the functional mechanisms of this gene are necessary, since the endoglin participates in a range of important cellular processes and more efforts should be made for genetic studies in the Brazilian population, considering the mixture of populations.

Angiogenesis in the progression of cutaneous squamous cell carcinoma: an immunohistochemical study of endothelial markers

OBJECTIVE: To demonstrate the role of angiogenesis in the progression of cutaneous squamous cell carcinoma. INTRODUCTION: Angiogenesis is a pivotal phenomenon in carcinogenesis. Its time course in cutaneous squamous cell carcinoma has not yet been fully established. METHODS: We studied the vascular bed in 29 solar keratoses, 30 superficially invasive squamous cell carcinomas and 30 invasive squamous cell carcinomas. The Chalkley method was used to quantify the microvascular area by comparing panendothelial (CD34) with neoangiogenesis (CD105) immunohistochemical markers. The vascular bed from non-neoplastic adjacent skin was evaluated in 8 solar keratoses, 10 superficially invasive squamous cell carcinomas and 10 invasive squamous cell carcinomas. RESULTS: The microvascular area in CD105-stained specimens significantly increased in parallel with cutaneous squamous cell carcinoma progression. However, no differences between groups were found in CD34 sections. Solar keratosis, superficially invasive squamous cell carcinoma and invasive squamous cell carcinoma samples showed significant increases in microvascular area for both CD34- and CD105-stained specimens compared with the respective adjacent skin. DISCUSSION: The angiogenic switch occurs early in the development of cutaneous squamous cell carcinoma, and the rate of neovascularization is parallel to tumor progression. In contrast to panendothelial markers, CD105 use allows a dynamic evaluation of tumor angiogenesis. CONCLUSION: This study demonstrated the dependence of skin carcinogenesis on angiogenesis.