| 1. |
- Borgfeldt, Christer, et al.
(författare)
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High tumor tissue concentration of urokinase plasminogen activator receptor is associated with good prognosis in patients with ovarian cancer
- 2003
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 107:4, s. 658-665
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Tidskriftsartikel (refereegranskat)abstract
- volved in tumor growth and metastasis. We assayed the components of the uPA system in homogenates of 64 primary epithelial ovarian tumors and 5 metastases and evaluated the association of these parameters to prognosis in the 51 malignant cases. The levels of uPA, PAI-2 and the uPA: PAI-I complex increased with progressive loss of histological differentiation (P-trend <0.001, <0.05 and <0.001). The level of PAI-I was higher in poorly than in well/moderately differentiated tumors (p = 0.03). The content of uPAR was lower in benign tumors as compared to borderline malignancies (p = 0.002), invasive primary tumors (p < 0.001), and metastases (p = 0.002). Surprisingly, the level of uPAR was lower in poorly differentiated as compared to both borderline (p = 0.01) and well differentiated malignant tumors (p = 0.005). Also, the level of uPAR was lower in advanced as compared to early stages of the disease (P-trend = 0.002). The median follow-up time for patients was 5.8 years. High tumor tissue levels of uPAR were associated with longer postoperative survival (HR = 0.4, 95% CI = 0.2-0.8, p = 0.01). In contrast, shorter survival was evident in patients with high tumor levels of uPA from 2 years on after operation (HR = 4.6, 95% CI = 1.2-17, p = 0.02). High tPA levels tended to be associated with shorter overall survival after 2 years (HR = 2.9, 95% 95% Cl = 0.9-9.8, p = 0.08). Although high tumor tissue content of uPAR was associated with a less aggressive phenotype characterized by well differentiated histology and longer survival, low content of uPAR in the poorly differentiated tumors and metastases presumably results from increased elimination of uPAR. (C) 2003 Wiley-Liss, Inc.
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| 2. |
- Fredstorp-Lidebring, M, et al.
(författare)
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Urokinase plasminogen activator and its inhibitor, PAI-1, in association with progression-free survival in early stage endometrial cancer
- 2001
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Ingår i: European Journal of Cancer. - 1879-0852. ; 37:18, s. 2339-2348
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Tidskriftsartikel (refereegranskat)abstract
- Components of the urokinase plasminogen activator (u-PA) system are involved in the metastatic process, and have accordingly been associated with clinical outcome in a variety of malignant tumours. We investigated the prognostic importance of u-PA and plasminogen activator inhibitor type 1 (PAI-1) in endometrial cancer, analysed with luminometric immunoassay (LIA) and enzyme-linked immunosorbent assay (ELISA), respectively. Two different cut-off levels were used: the median and the 80th percentile-the latter because of the low progression rate for patients with early stage (I-II) endometrial cancer. After a median follow-up time of 6.8 years, univariate analysis of patients with stage I-II disease (n=188) showed that high u-PA and high PAI-1 content was associated with a shorter progression-free survival (PFS), but at different cut-off levels, uPA at the median (P=0.003), and PAI-1 at the 80th percentile (P<0.001). Among the other factors, DNA ploidy status was most strongly correlated to PFS, followed by age (continuous), International Federation of Gynaecology and Obstetrics (FIGO) grade of differentiation, S-phase fraction and progesterone receptor (PgR) status. Bivariate analyses, including ploidy and one of the factors u-PA or PAI-1, showed that both add significant prognostic information. We conclude that u-PA and PAI-1 are promising prognostic factors in early stage endometrial cancer.
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| 3. |
- Koul, A., et al.
(författare)
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BRCA1 and BRCA2 mutations in ovarian cancer : Covariation with specific cytogenetic features
- 2000
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Ingår i: International Journal of Gynecological Cancer. - : BMJ. - 1048-891X .- 1525-1438. ; 10:4, s. 289-295
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Tidskriftsartikel (refereegranskat)abstract
- We analyzed 37 primary invasive carcinomas for BRCA1 and BRCA2 mutations by screening the entire coding regions of both genes. Seven predicted truncating mutations (four in BRCA1 and three in BRCA2) and one novel BRCA1 missense variant (S1542C) were identified (8/37, 22%). Two of the BRCA1 mutations were somatic changes, whereas the remaining three BRCA1 changes and all mutations of BRCA2 were found to be of germline origin. All eight BRCA-positive tumors were serous or seropapillary carcinomas (8/27 serous tumors, 30%), and all but one were poorly differentiated. The correlation between tumor karyotype and BRCA status showed that clonal chromosomal aberrations were present in all BRCA-positive tumors (8/8) compared with 20 of 29 BRCA-negative ones. The most consistently affected region in BRCA-positive tumors was the long arm of chromosome 6; alterations within this arm with a breakpoint in band 6q21 were seen in four of five BRCA1-positive and in two of three BRCA2-positive tumors, but only in four of 20 karyotypically abnormal tumors without BRCA mutations, suggesting that the genetic pathways of tumor progression differ in the two groups. The high frequency of germline BRCA mutations detected in this pilot study (16% of 37 invasive carcinomas) points to the need for more extended analyses of population-based series of patients to determine the true contribution of these predisposing genes to the overall incidence of ovarian cancer in this population.
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| 4. |
- Koul, Anjila, et al.
(författare)
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Distinct sets of gene alterations in endometrial carcinoma implicate alternate modes of tumorigenesis
- 2002
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Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 94:9, s. 2369-2379
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Endometrial carcinomas seem to carry a different prognosis depending on the presence or absence of concomitant complex atypical hyperplasia (hyperplasia). The molecular genetic profile of these two pathogenetic types, based on the genes reportedly mutated in these cancers, remains to be defined. Although microsatellite inability is reported in approximately 25% of endometrial carcinomas, its relation with the 2 pathogenetic types is not investigated. METHODS. To elucidate their underlying genetic changes, we analyzed 53 sporadic endometrial tumors, including 19 with and 34 without hyperplasia, for microsatellite instability (MSI), DNA ploidy (by flow cytometry), and for mutations in different genes. RESULTS. Microsatellite instability was present in 21%, DNA nondiploidy in 15%, and mutations in the PTEN, KRAS, CTNNB1/beta-catenin, TP53, and CDKN2A genes were detected in 32, 11, 13, 17, and 0% of the tumors, respectively. Microsatellite instability and mutations in these genes were present in tumors both with and without complex atypical hyperplasia. All cases with complex atypical hyperplasia were early stage (I-II) endometrioid tumors and associated with long progression free disease (P = 0.0004). Furthermore, most tumors with hyperplasia had low World Health Organization or International Federation of Gynecology and Obstetrics grade, had less myometrial invasion, and showed expression of estrogen receptors. All MSI tumors were diploid and had a significantly higher rate of PTEN mutations, but similar rates of KRAS, beta-catenin, and TP53 mutations compared with microsatellite stable tumors. TP53 mutations more often were found in nondiploid tumors but never in tumors with PTEN, KRAS, or beta-catenin mutations, and all PTEN mutations occurred in diploid tumors. CONCLUSIONS. Thus, PTEN, KRAS, beta-catenin, and TP53 mutations occurred in tumors both with and without hyperplasia, but PTEN and TP53 mutations were more common in tumors without hyperplasia. However, none of these genes seems to clearly distinguish tumors with and without hyperplasia, suggesting that other factors may be involved. Conversely, alterations in the PTEN and TP53 genes seem to define distinct subgroups of endometrial carcinoma, the former associated with diploidy and MSI, the latter with macroscopic chromosomal instability.
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| 5. |
- Koul, Anjila, et al.
(författare)
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TP53 protein expression analysis by luminometric immunoassay in comparison with gene mutation status and prognostic factors in early stage endometrial cancer
- 2002
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Ingår i: International Journal of Gynecological Cancer. - : BMJ. - 1048-891X .- 1525-1438. ; 12:4, s. 362-371
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the TP53 tumor suppressor gene have been shown to significantly correlate with poor prognosis in endometrial cancer. In the present study we have evaluated a luminometric immunoassay (LIA) for quantitative estimation of TP53 protein expression in 65 cytosol preparations from endometrial cancer, previously analyzed for mutations in TP53 exons 4-10. LIA showed high (greater than or equal to 0.6 ng/mg protein) expression of TP53 protein in all eight tumors with missense mutation, but high protein levels were also detected in 15 tumors with normal TP53 sequence. All four tumors with nonsense or frameshift mutations had low or no TP53 protein expression. LIA was further evaluated in a retrospective study of 201 cytosol samples from endometrial cancer. TP53 overexpression (>= 0.6 ng/mg protein) was observed in 22% of the tumors and correlated with nonendometrioid histology types (P = 0.005), poorly differentiated tumors (P = 0.001), higher FIGO grade (P = 0.001), DNA nondiploidy (P = 0.002), and high S-phase fraction (P = 0.03). After a median follow-up time of 6.8 years (range 0.7-9.9 years), 22 (13%) progressions were observed in the 175 patients with early stage (I-II) disease. TP53 overexpression (P = 0.04), FIGO grade 3 vs. 1 + 2 (P = 0.01), higher age (P = 0.02), and DNA nondiploidy (P < 0.001) showed significant correlation to shorter progression-free survival in these patients. We conclude that TP53 protein analysis by LIA provides an incomplete correlation to mutation status and cannot substitute for mutation analysis in assessment of prognosis in endometrial carcinoma. In comparison to TP53 overexpression and higher FIGO grades, DNA nonploidy status seems to be a better prognostic indicator to define a subset of early stage endometrial cancer patients who may benefit by adjuvant chemotherapy/radiotherapy.
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| 6. |
- Marthinsen, L, et al.
(författare)
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Intestinal spirochetosis in eight pediatric patients from Southern Sweden - A clinical, histopathological and ultrastructural study
- 2002
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 1600-0463. ; 110:7-8, s. 571-579
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Tidskriftsartikel (refereegranskat)abstract
- Intestinal spirochetes in humans have been recognized for more than a century, but it is still a matter of debate whether they are just commensal organisms or whether they cause colorectal disease. Most descriptions to date are of adult patients, while reports in the pediatric literature have been scarce. In a retrospective study we found eight children with intestinal spirochetosis. The findings, clinical as well as pathological, with light- and electron microscopy, are presented. In all patients, a 3 pm-thick layer of spirochetes was visualised on the luminal aspect of the epithelial cells covering the enterocytes and part of the gland openings. In five of the eight cases an inflammatory cell reaction was seen by light microscopy and in one patient a picture suggesting intracytoplasmatically located spirochetes was seen by electron microscopy. Despite partial or complete destruction of microvilli, spirochetes were still able to adhere to the enterocyte membranes. In three children there was a clear correlation between treatment and relief of symptoms. In four there was partial improvement and in one child no change in bowel-related symptoms. We believe that intestinal spirochetes may cause colorectal disease in children. Possible pathogenic mechanisms are discussed.
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| 7. |
- Nilsson, J, et al.
(författare)
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Screening for oesophageal adenocarcinoma : an evaluation of a surveillance program for columnar metaplasia of the oesophagus
- 2000
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 35:1, s. 6-10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Screening patients with columnar metaplasia of the oesophagus for adenocarcinoma is controversial owing to the low cancer incidence and diverging opinions as to whether screening improves the prognosis of these patients. Our aim was to evaluate a screening program for adenocarcinoma in patients with columnar metaplasia in the oesophagus, with focus on cancer incidence and costs.METHODS: One hundred and ninety-nine patients with columnar metaplasia of the oesophagus were identified through an endoscopy database, and the original patient records were reviewed.RESULTS: The patients were followed up for 797 years in total and during this time were subjected to 1071 upper gastrointestinal endoscopies. During the screening period 5 patients presented with adenocarcinoma; thus the cancer-incidence was 1 in 159 patient-years. The cost of detecting one cancer was 294,950 SEK (US$ 37,815). However, only four of the five patients were suitable for oesophagectomy, and of these, one patient turned out to have an advanced cancer. All patients developing cancer had columnar metaplasia of the oesophagus longer than 3 cm and specialized columnar epithelium (intestinal metaplasia/Barrett oesophagus).CONCLUSIONS: Low cancer incidence, high costs, and the doubtful prognosis for the patients with identified cancer question the benefits and cost-effectiveness of cancer screening among patients with columnar metaplasia in the oesophagus.
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| 8. |
- Willen, R, et al.
(författare)
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Similarity of uterine mucosa changes in patients treated by Raloxifen and Tamoxifen
- 2002
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Ingår i: Anticancer research. - 1791-7530. ; 22:2B, s. 1121-1125
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Tidskriftsartikel (refereegranskat)abstract
- Background: Selective estrogen receptor modulators (SERMS) like Tamoxifen and Raloxifen are used for menopausal symptoms, prevention of cardio-vascular diseases, osteoporosis and mammary carcinoma. Tamoxifen acts as an estrogen inhibitor on the mammary gland, but stimulates postmenopausal uterine mucosa in about 25% of cases while decreasing the risk of osteoporosis. Materials, Methods and Results: In three menopausal women, 56, 79 and 62 years of age, we found uterine mucosal changes similar to what is found in Tamoxifen-treated patients. Using light microscopy and immuno-histopathological techniques, partly cystic mucosa with both atrophic and proliferating glands was found. Strong stromal proliferation was also seen with the typical sharp-edged form of stromal cells and mitoses. A strong ostrogen and progesterone reaction was revealed with immuno-histopathological techniques in both gland and stromal parts. Conclusion: Taking into account the variable amount of different estrogen-receptor types in the uterine mucosa, we can not in the long run expect that no patient will react with estrogen-stimulation features on SERMs like Raloxifen. Further studies and thorough observations are needed to elucidate the true frequency of Raloxifen impact on the uterine mucosa.
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