Abstract The invasion of a tumour through tissue limiting basement membranes is the critical step in malignant growth. Gelatinases (MMP-2 and MMP-9) are endopeptidases capable of degrading extracellular and pericellular matrix proteins such as collagen IV, the major component of basement membranes. An over-expression of these gelatinases is generally found in malignant tumours and is linked to impaired prognosis in many cancer types. Tissue inhibitors of metalloproteinases (TIMPs), endogenous regulators of the MMP activity, have recently been introduced as multifunctional proteins, which have paradoxical roles in tumour growth. Little data exists on the clinical significance of the gelatinases and TIMPs in gynaecological cancers. In this study the clinical significance of the gelatinases was studied in endometrial and uterine cervical cancers by using immunohistochemical staining with specific antibodies. In epithelial ovarian cancer (EOC) these enzymes and their TIMPs were studied in the preoperative serum samples using ELISA assay. Additionally, sequential serum measurements were performed during chemotherapy to evaluate them as treatment response indicators. In endometrial cancer, MMP-9 positivity correlated to a poor histological differentiation and an advanced clinical stage. High MMP-2 expression correlated to a poor differentiation, and unfavourable survival in stage I cancers, with mortality rates of 5% and 19% in patients with MMP-2 negative versus intensively MMP-2 positive tumours, respectively. In cervical cancers high MMP-2 expression correlated to an increased mortality risk. High MMP-9 expression was connected to a good differentiation of a tumour. In EOC, a high circulating TIMP-1 value correlated to all the examined aggressive features of EOC, including poor survival. The serum measurements of TIMP-1 were uninformative about response evaluation during chemotherapy but paradoxically, an increase in gelatinases and TIMP-2 seemed to reflect a good response to treatment. In conclusion, the data from this study show that high MMP-2 expression in tumour tissue could be prognostic in endometrial and cervical cancer, and preoperative circulating TIMP-1 could serve as an additional prognostic marker in EOC. Studies with larger patient cohorts would be necessary to further explore the value of these enzymes in clinical practice in gynaecological cancers.

<p>Uvod: Karcinom jajnika predstavlja značajan zdravstveni problem.Karakteri&scaron;e ga najveća smrtnost od svih ginekolo&scaron;kih maligniteta. Najveći broj slučajeva karcinoma jajnika dijagostikuje se u uznapredovalim stadijumima bolesti (FIGO st. III i IV), kod kojih petogodi&scaron;nje preživljavanje iznosi ispod 30%, dok se svega 25% slučajeva otkrije u prvom stadijumu gde petogodi&scaron;nje preživljavanje iznosi preko 90%. Do danas nije otkrivena dijagnostička metoda za rano otkrivanje početnog karcinoma jajnika u op&scaron;toj populaciji koja je dovoljno osetljiva i specifična da bi se koristila kao &bdquo;screening&ldquo; metoda. Uspeh u lečenju karcinoma jajnika direktno zavisi od rano postavljene dijagnoze. Cilj istraživanja: Utvrditi značaj tumorskih markera Ca125, HE4, Roma indexa, konvencionalne i dopler transvaginalne sonografije u dijagnostici karcinoma jajnika. Metodologija: Istraživanje je sprovedeno kao prospektivna klinička studija, na Klinici za ginekologiju i aku&scaron;erstvo u Novom Sadu. Ispitivanjem je obuhvaćeno 238 pacijenktinja sa adneksalnim tumorom za operativno lečenje. Preoperativno svim pacijentkinjama je uzeta detaljna anamneza, urađen konvencionalni i dopler transvaginalni ultrazvučni pregled i uzeta krv za određivanje tumorskih markera CA125, HE4, Roma indexa. U zavisnosti od definitivnog patohistolo&scaron;kog nalaza pacijentkinje su podeljene u dve grupe. Grupu A ili ispitivanu grupu su činile ispitanice sa karcinomom i border line tumorima,a grupu B ili kontrolnu grupu,pacijentkinje sa benignim tumorima jajnika. Rezultati: Prosečna starost pacijentkinja je 53 godine. U ukupnom ispitivanom uzorku bilo je statistički značajno vi&scaron;e pacijentkinja u premenopauzi(59,2%) u odnosu na postmenopauzalne pacijentkinje. U ispitivanoj grupi najče&scaron;će zastupljen patohistolo&scaron;ki tip karcinoma je high-grade serozni cistadenokarcinom. Kod najvećeg broja pacijentkinja(49,4%) karcinom je dijagnostikovan u I stadijumu bolesti. U diferencijaciji karcinoma jajnika i benignih tumora jajnika, AUC vrednosti za HE4,Ca125 i Roma index su 0.933, 0.831 i 0.932. Senzitivnost HE4,Ca125,Roma indexa iznosi 0.797/ 0.734 / 0.823. Specifičnost HE4,Ca125, Roma indexa je 0.881 / 0.838 / 0.774. Senzitivnost konvencionalne i dopler transvaginalne sonografije je 0,937/ 0,750, a specifičnost je 0,736/ 0,931 respektivno.Kod pacijentkinja sa endometriozom, vrednost tumorskog markera HE4 je povi&scaron;ena samo kod 6% pacijentkinja, za razliku od vrednosti Ca125 koje su povi&scaron;ene kod 76% pacijentkinja sa endometriozom. Zaključak: Najsnažniji prediktori u diferencijaciji karcinoma od benignih tumora jajnika su: tumorski marker HE4, Roma index, indeks otpora protoku krvi kroz tumorsko tkivo (RI), neravan unutra&scaron;nji zid tumora i ekrescencije unutar tumora. Najbolju senzitivnost u detekciji karcinoma jajnika pokazala je konvencionalna transvaginalna sonografija u odnosu na druge dve ispitivane metode, dok najbolju specifičnost u odvajanju benignih tumora od karcinoma jajnika pokazuje dopler transvaginalna sonografija.</p> / <p>Background: Ovarian cancer represents very important world health issue. It is characterized by the highest mortality rate of all gynecological malignancies. The majority of ovarian cancer cases are diagnosed in advanced stages (FIGO III and IV) in which 5 year survival rate is less than 30%, and only 25% of cases are diagnosed in stage I with survival rate of 90%. So far no diagnostic method has been discovered that is specific and accurate enough to diagnose ovarian cancer in early stage in general population, so that it can be used as screening method. Success rate of treatment of ovarian cancer is dependent on the stage in which the diagnosis has been made. Objective: to determine the importance of tumor markers CA 125, HE4, Roma index, conventional and Doppler transvaginal ultrasound in diagnosis of ovarian cancer. Method: Research was undertaken as prospective study at Clinic for Gynecology and Obstetrics in Novi Sad. The analysis included 238 women with adnexal tumors indicated for surgery. Preoperatively detailed medical history, blood analysis (CA125,HE4,ROMA index), conventional and Doppler transvaginal ultrasound were done for all patients. Patients were divided into two groups depending on their definite pathohistological finding. Group A included patients with carcinoma and border line tumors. Group B (control group) included patients with benign ovarian tumors. Results: Average age of patient was 53 years. More patients were premenopausal (59.2%). The most frequent pathohistological type of carcinoma was high grade serous cystadenocarcinoma. In most cases diagnosis was made in stage I (49.4%). In differentiation between ovarian carcinoma and benign ovarian tumors AUC for HE4, Ca125and Roma index were 0.933,0.831,0.932. Sensitivity of HE4,Ca125 and Roma index is 0.797,0.734,0.832. Specificity of HE4,Ca125 and Roma index is 0.881,0.838,0.774. Sensitivity of conventional and transvaginal ultrasound is 0.937, 0.750, and specificity is 0.736 and 0.931 respectively. In patients with endometriosis tumor marker HE4 levels were elevated in only 6% of cases, while Ca125 levels were elevated in 76% of cases. Conclusion: The most important predictors in carcinoma/benign tumor differentiation are tumor markers HE4, Roma index, RI, uneven inner walls of tumor and ekrescency inside tumor. The highest sensitivity in ovarian cancer detection showed conventional transvaginal ultrasound when compared to two other used methods. The highest specificity in carcinoma/bening tumor differentiation showed doppler transvaginal ultrasound.</p>

NTRODUÇÃO: Neoplasias mucinosas primárias do ovário apresentam muitos pontos de controvérsias em relação ao seu padrão de diferenciação, sendo classificadas como tumores benignos, borderline e malignos.Elas também são classificadas em diferentes fenótipos, recentemente designadas como gastrointestinal e seromucinoso. Sua heterogeneidade tem produzido não somente dificuldades na classificação morfológica e no diagnóstico diferencial com neoplasias metastáticas, mas também na compreensão da patogênese e na interpretação imunoistoquímica. O fenótipo gastrointestinal tem sido pouco explorado em relação a possíveis diferenças entre os padrões de diferenciação gástrico e intestinal, desde que os dois são geralmente analisados juntos. Os tumores mucinosos borderline, considerado um estágio precoce da carcinogênese dos tumores mucinosos, são freqüentemente associados com pseudomixoma peritoneal (PMP), o qual foi recentemente relacionado a neoplasias mucinosas do apêndice cecal. O propósito deste estudo foi analizar os diferentes padrões morfológicos de apresentação dos tumores mucinosos do ovário e sua associação com o potencial de malignidade e o perfil imunoistoquímico. MATERIAL E MÉTODOS: Este estudo retrospectivo incluiu 72 tumores de 63 pacientes com diagnóstico patológico presumido de tumor mucinoso primário de ovário selecionados dos arquivos da Divisão de Patologia Cirúrgica da Faculdade de Medicina da Universidade de São Paulo, de 1996 a 2005. Todos as lâminas da população de pacientes foram revisadas e classificadas de acordo com os critérios da WHO. Marcação imunoistoquímica para produtos do gene de mucina (MUC1, MUC2, MUC5AC e MUC6), RE, RP, CK7, CK20, CA19.9 e CA125 foram feitos em tissue microarrays. RESULTADOS: Nossos resultados mostraram 28 tumores benignos, 35 borderline e 9 malignos distribuídos nos fenótipos: pilórico (11), intestinal (30), gastrointestinal (20), mülleriano (4) e misto (gastrointestinal e mülleriano) (7). Seis pacientes tinham PMP associados. O estudo imunoistoquímico foi realizado em 67 tumores. Os tumores pilóricos apresentaram-se mais freqüentemente como tumores benignos (72.7%) e tiveram um perfil imunoistoquímico diferente de MUC2 (p= 0.003) e CA19.9 (p= 0.04) quando comparado com o fenótipo intestinal. MUC1 foi mais expresso entre os tumores com diferenciação mülleriana (pura ou mista) (100%, p= 0.02) quando comparado aos tumores de outros fenótipos. Os receptores hormonais foram positivos somente no fenótipo mülleriano. Os tumores borderline foram mais freqüentes nos fenótipos intestinal e gastrointestinal (37.1% e 40%), e estavam associados a PMP em 25% dos casos. Todos os tumores ovarianos associados a PMP eram de tipo histológico borderline e com fenótipo intestinal. O perfil dos tumores borderline de tipo intestinal, mesmo nos casos sem PMP, foi distinto dos outros tumores mucinosos de tipo intestinal e caracterizado pela expressão XVII de MUC2 e CK20. A média de idade das pacientes com tumores borderline de tipo intestinal sem PMP foi menor que daquelas com PMP. CONCLUSÃO: O subgrupo de tumores mucinosos de ovário de fenótipo gastrointestinal é o mais freqüente, mas é hetetogênio e composto por uma população de células de tipos pilórico e intestinal que diferem entre si em relação ao potencial de malignidade e perfil imunoistoquímico. Os tumores de fenotipo intestinal são mais freqüentemente malignos e borderline. Os tumores ovarianos associados com PMP e provavelmente também a maioria dos tumores borderline de fenótipo intestinal, mesmo sem PMP, devem ser considerados como tumores secundários, quando uma origem em apêndice cecal parece a mais provável. / NTRODUCTION: Primary ovarian neoplasms of mucinous type carry many controversial points regarding their pattern of differentiation, classified as benign, borderline and malignant tumors. They are also classified into different morphological phenotypes, recently called as gastrointestinal and seromucinous. Their heterogeneity has produced not only difficulty into morphological classification and differential diagnostic with metastatic neoplasms, but also on understanding the pathogenesis and immunohistochemical interpretation. The gastrointestinal phenotype has been little explored with respect to possible differences between the gastric and intestinal morphological patterns of differentiation, since the two have generally been analyzed together. The mucinous borderline tumors, thought to be an intermediary stage of mucinous carcinogenesis, were frequently associated with pseudomyxoma peritonei (PMP), which was recently linked to appendiceal mucinous neoplasms. The purpose of the study was to analyze the different morphological patterns of presentation of mucinous ovarian tumors and their association with malignant potential and immunohistochemical profile. MATERIAL AND METHODS: This retrospective study included 72 tumors from 63 patients with pathological diagnosis of presumed primary mucinous ovarian tumor selected from the files of the Division of Surgical Pathology of University of Sao Paulo Medical School, from 1996 to 2005. All slides from the patient cohort were reviewed and classified according to WHO criteria. Immunohistochemical staining for mucin genes products (MUC1, MUC2, MUC5AC and MUC6), ER, PR, CK7, CK20, CA19.9 and CA125 were performed in tissue microarrays. RESULTS: Our results showed 28 benign, 35 borderline and 9 malignant tumors distributed in phenotypes: pyloric (11), intestinal (30), gastrointestinal (20), müllerian (4) and mixed (7) gastrointestinal and müllerian). Six patients had PMP associated. The immunohistochemical study was performed in 67 tumors. The pyloric tumors presented more frequently as benign tumors (72.7%) and had a differential immunohistochemical profile of MUC2 (p= 0.003) and CA19.9 (p= 0.04) when compared with intestinal phenotype. MUC1 was more expressed between tumors with müllerian differentiation (pure or mixed) (100%, p= 0.02) when compared with the others. The hormonal receptors were positive only in müllerian phenotype. Borderline tumors were more frequently of intestinal and gastrointestinal phenotypes (37.1% and 40%), and were associated to PMP in 25% of the cases. All ovarian tumors associated to PMP were of borderline histology and of intestinal type. The profile of intestinal borderline tumors, even in cases without PMP, was distinct from that of other primary mucinous tumors of the intestinal type and characterized by MUC2 and CK20 expression. The median age of patients with intestinal borderline tumors without PMP was lower than those with PMP. XIX CONCLUSION: The gastrointestinal subgroup of mucinous ovarian tumors is the more frequent, but it is heterogeneous and composed of pyloric, and intestinal cell population that differ regarding malignant potential and immunoprofile. The intestinal tumors are more frequently malignant and borderline. Ovarian tumors associated with PMP and probably most intestinal borderline tumors, even without PMP, should be considered as secondary tumor when the appendiceal origin seems the most probable.

by Cheung Kwok Kuen. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (leaves 111-130). / Chapter Chapter 1 --- General introduction of human ovarian cancer / Chapter 1.1 --- Epidemiology --- p.1 / Chapter 1.2 --- Symptoms and diagnosis --- p.4 / Chapter 1.3 --- Etiology --- p.5 / Chapter 1.3.1 --- Factors associated with decreased risks --- p.6 / Chapter 1.3.2 --- Factors associated with increased risks --- p.8 / Chapter 1.4 --- Classification of ovarian cancer --- p.12 / Chapter 1.5 --- Molecular basis of ovarian cancer --- p.18 / Chapter 1.6 --- Project aim --- p.29 / Chapter Chaper 2 --- "DOC-2, a differentially expressed gene in human ovarian cancer" / Chapter 2.1 --- Introduction --- p.32 / Chapter 2.2 --- Materials and Methods --- p.35 / Chapter 2.2.1 --- Expression of DOC-2 in human ovarian tissues --- p.35 / Chapter 2.2.1.1 --- Preparation of specimen --- p.35 / Chapter 2.2.1.2 --- Immunohistochemical studies of the expression of DOC-2 protein in human ovarian tissues --- p.35 / Chapter 2.2.1.3 --- Quantitation of immunoreactivity --- p.38 / Chapter 2.2.2 --- Effect of DOC-2 transfection on growth rate of the ovarian cancer cell lineSKOV3 --- p.39 / Chapter 2.2.2.1 --- Cell line --- p.39 / Chapter 2.2.2.2 --- Transfection of DOC-2 to SKOV3 ovarian carcinoma cell line --- p.39 / Chapter 2.2.2.3 --- Growth curve of the transfected ovarian carcinoma cell lines --- p.40 / Chapter 2.2.3 --- In vivo tumorigenicity study --- p.42 / Chapter 2.3 --- Results --- p.44 / Chapter 2.3.1 --- Expression of DOC-2 in human ovarian tissues --- p.44 / Chapter 2.3.2 --- Effects of DOC-2 transfected gene on the growth rate of the human ovarian cancer cell line SKOV3 --- p.46 / Chapter 2.3.2.1 --- Standard curves for calculating cell density from absorbance --- p.46 / Chapter 2.3.2.2 --- The effect of DOC-2 transfection on the growth rate of the human ovarian cancer cell line SKOV3 --- p.47 / Chapter 2.3.3 --- In vivo tumorigenicity --- p.48 / Chapter 2.4 --- Discussion --- p.50 / Chapter Chapter 3 --- DOC-2 expression in mouse embryonic development / Chapter 3.1 --- Introduction --- p.56 / Chapter 3.2 --- Materials and Methods --- p.60 / Chapter 3.2.1 --- Expression of murine homolog of DOC-2 (p96) during mouse embryonic development --- p.60 / Chapter 3.2.1.1 --- Preparation of paraffin-embedded mouse embryo sections --- p.60 / Chapter 3.2.1.2 --- Preparation of OCT-embedded mouse embryo sections --- p.61 / Chapter 3.2.1.3 --- Immunohistochemistry of murine homolog of DOC-2 (p96) on mouse embryos --- p.61 / Chapter 3.2.2 --- Effect of antibody blocking for DOC-2 protein on the growth of embryonic kidney in vitro --- p.62 / Chapter 3.3 --- Results --- p.64 / Chapter 3.4 --- Discussion --- p.69 / Chapter Chapter 4 --- Apoptosis / Chapter 4.1 --- Introduction --- p.72 / Chapter 4.1.1 --- Current methods for the detection of apoptosis --- p.74 / Chapter 4.1.1.1 --- Agarose gel electrophoresis --- p.75 / Chapter 4.1.1.2 --- Flow cytometric analysis --- p.76 / Chapter 4.1.1.3 --- 3-OH end labelling --- p.77 / Chapter 4.1.1.4 --- Nuclease assay --- p.78 / Chapter 4.1.2 --- Apoptosis in normal physiology and oncogenesis --- p.78 / Chapter 4.1.3 --- p53 and apoptosis --- p.80 / Chapter 4.1.4 --- bcl-2 and apoptosis --- p.83 / Chapter 4.2 --- Materials and Methods --- p.92 / Chapter 4.2.1 --- Expression of p53 and bcl-2 in human ovarian tissues --- p.92 / Chapter 4.2.1.1 --- Preparation of specimens --- p.92 / Chapter 4.2.1.2 --- Immunohistochemical studies of the expression of p53 and bcl-2 proteins in ovarian tissue --- p.92 / Chapter 4.2.2 --- In stiu terminal transferase-mediated dUTP nick and labelling (TUNEL) --- p.94 / Chapter 4.3 --- Results --- p.96 / Chapter 4.3.1 --- Expression of p53 and bcl-2 in human ovarian tissues --- p.96 / Chapter 4.3.2 --- Apoptosis in human ovarian tissues --- p.99 / Chapter 4.4 --- Discussion --- p.101 / Chapter Chapter 5 --- Concluding Remarks --- p.108 / References --- p.111 / Appendix --- p.131 / Figures and legend --- p.138

NTRODUÇÃO: Neoplasias mucinosas primárias do ovário apresentam muitos pontos de controvérsias em relação ao seu padrão de diferenciação, sendo classificadas como tumores benignos, borderline e malignos.Elas também são classificadas em diferentes fenótipos, recentemente designadas como gastrointestinal e seromucinoso. Sua heterogeneidade tem produzido não somente dificuldades na classificação morfológica e no diagnóstico diferencial com neoplasias metastáticas, mas também na compreensão da patogênese e na interpretação imunoistoquímica. O fenótipo gastrointestinal tem sido pouco explorado em relação a possíveis diferenças entre os padrões de diferenciação gástrico e intestinal, desde que os dois são geralmente analisados juntos. Os tumores mucinosos borderline, considerado um estágio precoce da carcinogênese dos tumores mucinosos, são freqüentemente associados com pseudomixoma peritoneal (PMP), o qual foi recentemente relacionado a neoplasias mucinosas do apêndice cecal. O propósito deste estudo foi analizar os diferentes padrões morfológicos de apresentação dos tumores mucinosos do ovário e sua associação com o potencial de malignidade e o perfil imunoistoquímico. MATERIAL E MÉTODOS: Este estudo retrospectivo incluiu 72 tumores de 63 pacientes com diagnóstico patológico presumido de tumor mucinoso primário de ovário selecionados dos arquivos da Divisão de Patologia Cirúrgica da Faculdade de Medicina da Universidade de São Paulo, de 1996 a 2005. Todos as lâminas da população de pacientes foram revisadas e classificadas de acordo com os critérios da WHO. Marcação imunoistoquímica para produtos do gene de mucina (MUC1, MUC2, MUC5AC e MUC6), RE, RP, CK7, CK20, CA19.9 e CA125 foram feitos em tissue microarrays. RESULTADOS: Nossos resultados mostraram 28 tumores benignos, 35 borderline e 9 malignos distribuídos nos fenótipos: pilórico (11), intestinal (30), gastrointestinal (20), mülleriano (4) e misto (gastrointestinal e mülleriano) (7). Seis pacientes tinham PMP associados. O estudo imunoistoquímico foi realizado em 67 tumores. Os tumores pilóricos apresentaram-se mais freqüentemente como tumores benignos (72.7%) e tiveram um perfil imunoistoquímico diferente de MUC2 (p= 0.003) e CA19.9 (p= 0.04) quando comparado com o fenótipo intestinal. MUC1 foi mais expresso entre os tumores com diferenciação mülleriana (pura ou mista) (100%, p= 0.02) quando comparado aos tumores de outros fenótipos. Os receptores hormonais foram positivos somente no fenótipo mülleriano. Os tumores borderline foram mais freqüentes nos fenótipos intestinal e gastrointestinal (37.1% e 40%), e estavam associados a PMP em 25% dos casos. Todos os tumores ovarianos associados a PMP eram de tipo histológico borderline e com fenótipo intestinal. O perfil dos tumores borderline de tipo intestinal, mesmo nos casos sem PMP, foi distinto dos outros tumores mucinosos de tipo intestinal e caracterizado pela expressão XVII de MUC2 e CK20. A média de idade das pacientes com tumores borderline de tipo intestinal sem PMP foi menor que daquelas com PMP. CONCLUSÃO: O subgrupo de tumores mucinosos de ovário de fenótipo gastrointestinal é o mais freqüente, mas é hetetogênio e composto por uma população de células de tipos pilórico e intestinal que diferem entre si em relação ao potencial de malignidade e perfil imunoistoquímico. Os tumores de fenotipo intestinal são mais freqüentemente malignos e borderline. Os tumores ovarianos associados com PMP e provavelmente também a maioria dos tumores borderline de fenótipo intestinal, mesmo sem PMP, devem ser considerados como tumores secundários, quando uma origem em apêndice cecal parece a mais provável. / NTRODUCTION: Primary ovarian neoplasms of mucinous type carry many controversial points regarding their pattern of differentiation, classified as benign, borderline and malignant tumors. They are also classified into different morphological phenotypes, recently called as gastrointestinal and seromucinous. Their heterogeneity has produced not only difficulty into morphological classification and differential diagnostic with metastatic neoplasms, but also on understanding the pathogenesis and immunohistochemical interpretation. The gastrointestinal phenotype has been little explored with respect to possible differences between the gastric and intestinal morphological patterns of differentiation, since the two have generally been analyzed together. The mucinous borderline tumors, thought to be an intermediary stage of mucinous carcinogenesis, were frequently associated with pseudomyxoma peritonei (PMP), which was recently linked to appendiceal mucinous neoplasms. The purpose of the study was to analyze the different morphological patterns of presentation of mucinous ovarian tumors and their association with malignant potential and immunohistochemical profile. MATERIAL AND METHODS: This retrospective study included 72 tumors from 63 patients with pathological diagnosis of presumed primary mucinous ovarian tumor selected from the files of the Division of Surgical Pathology of University of Sao Paulo Medical School, from 1996 to 2005. All slides from the patient cohort were reviewed and classified according to WHO criteria. Immunohistochemical staining for mucin genes products (MUC1, MUC2, MUC5AC and MUC6), ER, PR, CK7, CK20, CA19.9 and CA125 were performed in tissue microarrays. RESULTS: Our results showed 28 benign, 35 borderline and 9 malignant tumors distributed in phenotypes: pyloric (11), intestinal (30), gastrointestinal (20), müllerian (4) and mixed (7) gastrointestinal and müllerian). Six patients had PMP associated. The immunohistochemical study was performed in 67 tumors. The pyloric tumors presented more frequently as benign tumors (72.7%) and had a differential immunohistochemical profile of MUC2 (p= 0.003) and CA19.9 (p= 0.04) when compared with intestinal phenotype. MUC1 was more expressed between tumors with müllerian differentiation (pure or mixed) (100%, p= 0.02) when compared with the others. The hormonal receptors were positive only in müllerian phenotype. Borderline tumors were more frequently of intestinal and gastrointestinal phenotypes (37.1% and 40%), and were associated to PMP in 25% of the cases. All ovarian tumors associated to PMP were of borderline histology and of intestinal type. The profile of intestinal borderline tumors, even in cases without PMP, was distinct from that of other primary mucinous tumors of the intestinal type and characterized by MUC2 and CK20 expression. The median age of patients with intestinal borderline tumors without PMP was lower than those with PMP. XIX CONCLUSION: The gastrointestinal subgroup of mucinous ovarian tumors is the more frequent, but it is heterogeneous and composed of pyloric, and intestinal cell population that differ regarding malignant potential and immunoprofile. The intestinal tumors are more frequently malignant and borderline. Ovarian tumors associated with PMP and probably most intestinal borderline tumors, even without PMP, should be considered as secondary tumor when the appendiceal origin seems the most probable.

Dissertation (Ph.D.)--University of South Florida, 2008. / Includes vita. Also available online. Includes bibliographical references.

Microarray expression analysis was carried out to identify genes with a role in epithelial ovarian cancer (EOC). The U133A Affymetrix GeneChipRTM was used to determine the expression patterns of the 3p25.3-ptel genes represented on the microarray in 14 primary cultures of normal ovarian surface epithelial (NOSE) samples, 25 frozen malignant ovarian tumor samples and four EOC cell lines. Seven genes with differential expression patterns in the tumor samples compared to the NOSE samples were identified as candidates for further analysis, starting with ARPC4, SRGAP3 and ATP2B2. Although none of the candidates had been previously studied in ovarian cancer, several had either family or pathway members that had. Expression patterns seemed unaffected by either tumor histopathological subtype or the allelic imbalances observed with loss of heterozygosity (LOH) analysis. The absence of association with genomic context suggested that differential expression was the result of transcriptional regulation rather than direct targeting.

Dissertation (Ph.D.)--University of South Florida, 2008. / Title from PDF of title page. Document formatted into pages; contains 187 pages. Includes vita. Includes bibliographical references.

Thesis (Ph.D. in Experimental Pathology, Program in Cancer Biology) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 144-158). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

No description available.