Background: Prostate Cancer (PC) is a common and highly variable disease. Using current diagnostic methods, the prostate specific antigen (PSA) blood test and histological grading of prostate tissue needle biopsies, it is often difficult to evaluate whether the patient has a PC that requires active treatment or not. The absolute majority of all 10,000 cases of PCs diagnosed annually in Sweden have tumours graded as Gleason score (GS) 6-7 and a PSA value in blood below 10. Many of these are harmless and can be left without active treatment and hence spared problematic post-therapy side-effects, others are highly malignant and require early diagnosis and treatment. Better prognostic markers are needed and the aim of this study was to evaluate prognostic markers and to test if these markers could identify patients with indolent tumours. Methods: We have studied tumour material from 419 men consecutively diagnosed with PC at transurethral resection (1975-1990). The majority of these patients (295) had no metastasis at diagnosis and was not given any curative treatment and only hormonal treatment upon symptoms from metastatic progression. Standard histological sections and tissue microarrays (TMA) from these tumours and surrounding normal prostate tissue were stained and evaluated for cell proliferation (Ki67), blood vessels (endoglin and von Willebrand factor, vWf) and the extracellular matrix component hyaluronan (HA). An orthotopic rat PC model was used to explore hyaluronan staining, hyaluronic acid synthase (HAS)-1 mRNA levels and the effect of local HA treatment on tumour growth. Results: Tumour cell proliferation (Ki67) and the density of intra-tumoural endoglin stained blood vessels were independent prognostic markers (i.e. they added prognostic information to the conventional prognostic markers; clinical stage and GS). None of the GS 6 patients with low staining for both Ki67 and endoglin died of PC within 15 years of follow-up. High HA staining in the tumour epithelium and stroma was a negative prognostic marker of cancer specific survival but they were not independent of GS. High HA staining and high vascular density in the stroma of the surrounding morphologically normal prostate were prognostic for short cancer specific survival. Implantation of tumour cells in the normal rat prostate resulted in an increase in HA and HAS-1 mRNA levels in the prostate tissue surrounding prostate tumours. Concurrently intra-prostatic injection of HA also stimulated tumour growth. Conclusions: By evaluating both tumour cell proliferation (Ki67) and vascular density, it is possible to identify patients with very low risk of cancer specific death in the absence of active treatment. Prostate tumours influence the surrounding non-malignant prostate tissue, for example they cause an increased angiogenesis and synthesis of hyaluronan. Such responses can possibly be used to diagnose PC and to evaluate PC aggressiveness.

Made available in DSpace on 2014-12-17T15:32:16Z (GMT). No. of bitstreams: 1 MarceloGV.pdf: 2007167 bytes, checksum: 5ee7e9c9bd56fd72fecb1874fb64a80e (MD5) Previous issue date: 2008-02-26 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Angiogenesis, a fundamental mechanism in tumor development, is used for differential diagnosis and prognosis purposes in various neoplasias of the head and neck. This study proposes to assess angiogenic activity using immunohistochemical expression by anti-CD105 and anti-CD34 antibodies in 20 cases of hemangiomas and 20 cases of oral pyogenic granulomas, in addition to determining the usefulness of these markers as one of the differential diagnosis resources for these two oral lesions. The results showed no statistically significant difference between microvascular count (MVC) means determined by anti-CD105 (p = 0.803) and anti-CD34 (p = 0.279) antibodies. The mean number of vessels obtained by MVC in the oral hemangiomas immunostained by anti-CD105 and anti-CD34 was 18.75 and 59.72, respectively, whereas in the oral pyogenic granulomas, the mean number was 20.22 and 48.09 respectively. It was also shown that CD34 was more effective than CD105 in identifying blood vessels. However, it must be pointed out that the anti-CD105 antibody seems to be more related to vascular neoformation. Overall, this assay reinforces the role of angiogenic factors in the etiopathogenesis of hemangiomas and oral pyogenic granulomas, but the results showed that angiogenesis quantification cannot be used as a differential diagnosis parameter between the two lesions analyzed / A angiog?nese ? um mecanismo fundamental para o desenvolvimento tumoral, sendo utilizada para fins de diagn?stico diferencial e determina??o de progn?stico em v?rias neoplasias de cabe?a e pesco?o. Este trabalho se prop?s avaliar a atividade angiog?nica atrav?s da express?o imuno-histoqu?mica dos anticorpos anti-CD105 e anti-CD34 em 20 casos de hemangiomas e 20 casos de granulomas piog?nicos orais, al?m de averiguar a utilidade destes marcadores como um dos recursos de diagn?stico diferencial para estas duas les?es orais. Os resultados deste experimento demonstraram que n?o houve diferen?a estatisticamente significativa entre as m?dias de contagem microvascular (MVC) determinadas pelos os anticorpos anti-CD105 (p=0,803) e anti-CD34 (p=0,279). O n?mero m?dio dos vasos obtidos pela MVC nos esp?cimes de hemangiomas orais imunomarcados pelo anti-CD105 e anti-CD34 foram respectivamente 18,75 e 59,72, enquanto nos granulomas piog?nicos orais, o n?mero m?dio dos vasos obtidos pela MVC pelo anti-CD105 e anti-CD34 foram respectivamente 20,22 e 48,09. Foi verificado, tamb?m, que o CD34 foi mais efetivo na identifica??o de vasos sang??neos quando comparado com o CD105. Entretanto, faz-se necess?rio destacar, que o anticorpo anti-CD105 parece estar mais relacionado com a neoforma??o vascular. Em linhas gerais, este ensaio refor?a a participa??o dos fatores angiog?nicos na etiopatog?nese dos hemangiomas e granulomas piog?nicos orais, por?m os resultados mostraram que a quantifica??o da angiog?nese n?o pode ser utilizada como par?metro de diagn?stico diferencial entre as duas les?es analisadas