Increased expression of the RIalpha subunit of the cAMP-dependent protein kinase A is associated with advanced stage ovarian cancer. (1/526)

The primary element in the cAMP signal transduction pathway is the cAMP-dependent protein kinase (PKA). Expression of the RIalpha subunit of type I PKA is elevated in a variety of human tumours and cancer cell lines. The purpose of this study was to assess the prognostic importance of RIalpha expression in patients with ovarian cancer. We have evaluated the expression of RIalpha in a panel of human ovarian tumours (n = 40) and five human ovarian cancer cell lines using quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. The human ovarian cell lines OAW42 and OTN14 express high endogenous levels of RIalpha mRNA and protein (at significantly higher mRNA levels than high tissue expressors, P < 0.05). The ovarian cell line A2780 expresses low endogenous levels of RIalpha mRNA and protein (also at higher mRNA levels than low tissue expressors, P < 0.05). Quantitative RT-PCR revealed no significant difference in RIalpha mRNA expression between different ovarian histological subtypes in this study. No associations were found between RIalpha mRNA expression and differentiation state. RIalpha mRNA expression was significantly associated with tumour stage (P = 0.0036), and this remained significant in univariate analysis (P = 0.0002). A trend emerged between RIalpha mRNA expression levels and overall survival in univariate analysis (P = 0.051), however, by multivariate analysis, stage remained the major determinant of overall survival (P = 0.0001). This study indicates that in ovarian epithelial tumours high RIalpha mRNA expression is associated with advanced stage disease. RIalpha expression may be of predictive value in ovarian cancer and may be associated with dysfunctional signalling pathways in this cancer type.  (+info)

The expression of CCAAT/enhancer binding protein (C/EBP) in the human ovary in vivo: specific increase in C/EBPbeta during epithelial tumour progression. (2/526)

The CCAAT/enhancer binding protein (C/EBP) family of transcription factors is involved in metabolism and differentiation of cells, especially in rodent liver cells and adipocytes. Their roles in vivo and in particular during pathophysiological conditions in humans are largely unknown. We have investigated the presence of C/EBPalpha, -beta, -delta and -zeta in normal ovaries and in epithelial ovarian tumours of different stages. Immunohistochemical experiments demonstrated that C/EBPalpha and C/EBPbeta were preferentially expressed in epithelial/tumour cells irrespective of stage or grade of the tumour. C/EBPbeta was located in the nuclei of the cells, in contrast to C/EBPalpha, which was present only in the cytoplasm of these cells. The nuclear localization of C/EBPbeta indicates an active role of this transcription factor in tumour cells, whereas the cytoplasmic distribution suggests a more passive function of C/EBPalpha. C/EBPdelta and -zeta demonstrated a more diverse distribution with predominant localization to epithelial cells, but stromal distribution was also noted. The intracellular distribution was confined to both the nucleus and the cytoplasm for C/EBPdelta and -zeta. Western blotting demonstrated that C/EBPalpha, -beta, -delta and -zeta were present in a majority of the samples. The amount of C/EBPbeta increased markedly with malignancy, i.e. with degree of dedifferentiation, while the other members of the C/EBP family displayed a more constant expression level. These results demonstrate an association between the expression of members of the C/EBP family and the formation of epithelial ovarian tumours, with C/EBPbeta as a potential marker for these tumours. As C/EBPbeta is known to be expressed during proliferation of cells in vitro, it may participate in the proliferative process of ovarian epithelial tumour cells in vivo and play a central role in tumour progression.  (+info)

Overexpression of H-Ryk in mouse fibroblasts confers transforming ability in vitro and in vivo: correlation with up-regulation in epithelial ovarian cancer. (3/526)

Abnormalities in the function of receptor tyrosine kinases (RTKs) have been demonstrated to be important in the pathogenesis of cancer. H-Ryk, a new member of the RTK family, is an unusual RTK in that it is catalytically inactive because of amino acid substitutions of conserved residues in the catalytic domain. We show by immunohistochemistry that it is expressed in the epithelium, stroma, and blood vessels of normal tissues. Evaluation of a panel of 33 primary ovarian tumors (2 benign, 8 borderline, and 23 malignant) was performed. H-Ryk was overexpressed in borderline and malignant ovarian tumors. In serous and clear cell subtypes, there was increased expression in the epithelium, stroma, and blood vessels. Consistent with this observation, overexpression of H-Ryk in the mouse fibroblast cell line NIH3T3 induces anchorage-independent growth and tumorigenicity in nude mice. This implies that overexpression of the receptor can be transforming and may therefore be significant in the pathogenesis of ovarian cancer.  (+info)

Borderline ovarian tumours in Vaud, Switzerland: incidence, survival and second neoplasms. (4/526)

Between 1976 and 1996, 176 borderline ovarian tumours were registered in the Cancer Registry of the Swiss canton of Vaud, corresponding to an age-adjusted incidence (world standard) of 2.7 in 100,000. Incidence rose from 1.7 per 100,000 during 1976-81 to 2.7 per 100,000 during 1987-91, and then levelled off; 58% of cases were serous and 41% mucinous. Relative survival was 94% at 10 years; 18 second neoplasms were observed, compared with 10.3 expected, and there was a significant excess of invasive ovarian cancers (four observed, including three synchronous, compared with 0.4 expected).  (+info)

Three dimensional ultrasound and power doppler in assessment of uterine and ovarian angiogenesis: a prospective study. (5/526)

AIM: To determine whether three-dimensional power Doppler can improve the recognition of pelvic tumor morphology and angiogenesis. METHODS: Using this technique we analyzed 180 adnexal masses and 110 uterine lesions. Tumor volume, morphology, and vascularity were evaluated in each patient. Irregular and randomly dispersed vessels with complex branching depicted by comprehensive three dimensional display were suggestive of pelvic malignancy, while linear-like vascular morphology, single vessel arrangement and regular branching were typical for benign structures. RESULTS: Addition of qualitative analysis of vascular architecture of adnexal tumor to morphological parameters reached 96.15% sensitivity and 98.73% specificity. When endometrial lesions were prospectively analyzed, sensitivity and specificity were 91.67% and 98.49%, respectively. Because the lowest positive predictive value of 16.67% was obtained for myometrial lesions, this method should not be advised for their eva luation. CONCLUSION: Good results achieved by three dimensional ultrasound can be explained by improved recognition of the pelvic lesion anatomy, characterization of the surface features, detection of the tumor infiltration, and precise depiction of the size and volume. Three dimensional power Doppler imaging can detect structural abnormalities of the malignant tumor vessels, such as arteriovenous shunts, microaneurysms, tumoral lakes, disproportional calibration, coiling, and dichotomous branching. Therefore it enhances and facilitates the morphologic and functional evaluation of both benign and malignant pelvic tumors.  (+info)

Evaluation of the tyrosine kinase domain of the Met proto-oncogene in sporadic ovarian carcinomas*. (6/526)

Most of the ovarian cancers originate from the ovarian surface epithelium derived from the coelomic mesothelium. The Met proto-oncogene encodes a transmembrane tyrosine kinase receptor (Met) that has the capacity to regulate cell proliferation and differentation and it is activated by hepatocyte growth factor. Trisomy of chromosome 7 and Met protein overexpression have been were observed in ovarian carcinomas, the papillary renal cancers and other solid tumors. Frequent mutations of Met proto-oncogene have been found in hereditary papillary renal cancer (HPRC) and most of the mutations are located in the tyrosine kinase domain. The aim of this study to perform a mutation analysis of exons 17 19 of Met proto-oncogene in epithelial ovarian tumors (EOTs). We have examined 24 tumor samples from patients, operated with EOTs. Mutation was detected in exon 18 in only one sample of 24 EOTs. Our results indicate that mutations located in the Met proto-oncogene is not a common event in EOT. It is not clear whether the mutation plays a role in the tumorigenesis or progression of EOT or not.  (+info)

Prognostic significance of p53 expression in advanced-stage ovarian serous borderline tumors. (7/526)

The purpose of this study was to investigate the frequency of p53 overexpression in the primary ovarian tumors of patients with stages II and III serous borderline tumors (SBTs) and to determine the relationship between p53 overexpression and risk of progression/recurrence and survival. Of 112 patients with stages II-IV SBTs, paraffin-embedded tissue from the primary ovarian tumor was available in 68 cases. Immunohistochemical staining for p53 was performed. Clinical information was abstracted from the medical records. The major end points selected for analysis were time to progression/relapse, disease-free survival, overall survival, and cause-specific survival. Univariate and multivariate regression analyses were also performed. The median patient age was 37 years (range, 17-67 years). Twenty-two patients had stage II disease, and 46 had stage III disease. The mean follow-up time was 105 months. Nineteen patients (28%) had either disease progression (1 patient) or relapse (18 patients). Eleven patients died: 10 patients died of their tumor, and 1 patient died of other causes. Thirteen cases (19%) had positive immunostaining for p53. Overexpression of p53 was significantly associated with an increased probability of progression/recurrence (P = 0.005) and a decreased overall survival (P = 0.012). After adjusting for age, International Federation of Gynecology and Obstetrics (FIGO) stage, the presence of residual tumor, and the presence of invasive implants, patients whose tumors overexpressed p53 had a 4-fold increased risk of progression/ recurrence. Similarly, women whose tumor overexpressed p53 had an approximately 6-fold increased risk of death. p53 overexpression in the ovarian tumors of patients with stage II and III SBTs is significantly associated with increased probability of relapse and decreased overall survival. This information should provide better prognostic data to patients and their families and allow us to select patients who might benefit from postoperative treatment.  (+info)

Allelotyping defines minimal imbalance at chromosomal region 17q25 in non-serous epithelial ovarian cancers. (8/526)

Allelic deletions of multiple chromosome 17q loci in sporadic ovarian cancer of epithelial origin suggest that inactivation of tumor suppressor gene(s) in these regions may be important for ovarian tumorigenesis. To further define the pattern of allelic imbalance in epithelial ovarian tumors of different histologies, a PCR-based assay was used to assess loss of heterozygosity (LOH) of polymorphic markers representative of TP53, BRCA1, NME1 and GH1, and region 17q23-25. LOH was observed for at least one marker in 68% of malignant tumors (n=60) and in 18% tumors of borderline malignancy (n=11), but not in benign tumors (n=5). The highest frequency of LOH in malignant tumors (64%) was observed with D17S801 on 17q25. Ten of 39 malignant ovarian tumors displaying LOH of at least one 17q marker, displayed a LOH pattern enabling the determination of a minimal region of overlapping deletion defined by D17S795 and D17S801. One borderline tumor also displayed an interstitial LOH pattern that overlapped this 17q25 minimal region of deletion. The histologies of malignant tumors displaying a pattern indicative of interstitial 17q deletions were of the endometrioid, clear cell and mucinous epithelial types. As the minimal region of overlap defined by these tumors overlap regions deleted in malignant tumors of all histologic types, and in a tumor of borderline malignancy, the 17q25-tumor suppressor may be implicated in the development of all types of epithelial ovarian tumors.  (+info)