| 1. |
- Arbyn, M, et al.
(författare)
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Clinical utility of HPV-DNA detection: Triage of minor cervical lesions, follow-up of women treated for high-grade CIN: An update of pooled evidence.
- 2005
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 99:3, Suppl 1, s. 7-11
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Human papilloma virus (HPV) testing and repeat cytology are both proposed as methods to triage women with minor cytological cervical lesions. By triage, those women can be identified who need referral for diagnostic exploration with colposcopy and/or biopsy. Methods. We conducted meta-analyses of reported studies on the accuracy to detect high-grade cervical intra-epithelial neoplasia or worse disease (CIN2+) in women with ASCUS or LSIL. We also performed meta-analyses to examine the best predictor of recurrence of CIN after treatment for CIN2 or CIN3. Results. We found that HPV testing using the Hybrid Capture II test is more effective (more sensitive, equally specific) than cytology for the triage of patients with ASCUS Pap smears. Because of the high rate of HPV positivity, this is not the case for patients with LSIL. Studies concerning post-treatment follow-Lip were heterogeneous. In general, HPV testing performed better than follow-up cytology to predict success or failure of treatment (significantly higher sensitivity, not significantly lower specificity). Conclusions. Overall, in comparison with follow-up cytology, HPV DNA testing is more sensitive and equally specific for triage of ASCUS cases and for predicting recurrence of CIN in women treated for high-grade CIN.
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| 2. |
- Casslén, Vera, et al.
(författare)
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Ovarian cancer cells stimulate uPA gene expression in fibroblastic stromal cells via multiple paracrine and autocrine mechanisms.
- 2009
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 115, s. 121-126
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Expression of uPA mRNA is massively up-regulated in the stroma of poorly differentiated ovarian tumors. We hypothesized that this expression was induced by paracrine signals from the epithelial tumor cells, and established an in vitro model of ovarian cancer microenvironment to study intercellular cross-talk. METHODS: ES-2 clear cell carcinoma cells were grown in tissue culture inserts in a double-chamber system with fibroblastic stromal LEP cells embedded in Matrigel. Binding-site directed antibodies were used to neutralize soluble cytokines in ES-2 conditioned medium (CM) before incubation with LEP cells. Real time PCR measured uPA mRNA in LEP cells, as well as mRNA for cytokines in both cell types. RESULTS: Co-culture with ES-2 cells as well as incubation with ES-2 CM induced uPA mRNA in LEP cells about two-fold. In short time (12 h) incubation of LEP cells with CM, antibodies to EGF and bFGF reduced induction of uPA mRNA, suggesting that these cytokines function as paracrine signals. EGF mRNA and bFGF mRNA were also found in ES-2 cells. At longer incubation (24 h) antibodies to bFGF, HB-EGF, HGF, IGF-1, and IL-1alpha reduced uPA mRNA induction, suggesting an autocrine function for these cytokines in LEP cells. In fact, expression of the same five cytokines was up-regulated in LEP cells exposed to CM. CONCLUSION: We identified two cytokines as paracrine signals, and five cytokines as autocrine signals in ovarian cancer cell induced up-regulation of uPA mRNA in stromal fibroblastic cells. It is crucial to understand intra-tumoral cross-talk, since it can offer new therapeutic approaches.
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| 3. |
- Hellberg, Dan, et al.
(författare)
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Pitfalls in immunohistochemical validation of tumor marker expression : exemplified in invasive cancer of the uterine cervix
- 2009
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 112:1, s. 235-240
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To study if immunohistochemical expression of tumor markers as prognostic predictors is influenced by clinical stage, adjustments for expression of other tumor markers and histological type in cervical cancer. METHODS: The study included 129 women with squamous cell cancer and 29 women with adenocarcinomas. Expression of 9 tumor markers relevant for cervical cancer and selected to represent different mechanisms in carcinogenesis was analysed. These were Ki-67, c-myc, LRIG1, p-53, p-27, CD44, VEGF, Cox-2 and CD4+. RESULTS: In late-stage cancer a higher number of tumor-infiltrating CD4 positive cells were associated with a favourable prognosis while a higher Ki-67 index with a poor prognosis. In early-stage cancer a high LRIG1 expression was associated with a favourable prognosis. Significantly different expressions were found at early-stage versus at late-stage squamous cell cancer for VEGF, p27 and LRIG1 which were all more strongly expressed in early stages. Adjustments for all selected tumor markers and clinical stage converted VEGF and LRIG1 expression from non-significant to significant prognostic predictors while the association between p53 expression and good prognosis was strengthened. Adjustments for Cox-2 and c-myc had the strongest impact on VEGF as a prognosis predictor and LRIG1 was most influenced by adjustment for p53. All correlations became non-significant when women with adenocarcinoma and other invasive tumor types were included. CONCLUSIONS: Failure to analyse clinical stages separately, failure to adjust for expression of relevant concurrent tumor markers and inclusion of different histological subtypes into the same study group may lead to false conclusions regarding the significance of prognostic tumor markers.
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| 4. |
- Henic, Emir, et al.
(författare)
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EGF-stimulated migration in ovarian cancer cells is associated with decreased internalization, increased surface expression, and increased shedding of the urokinase plasminogen activator receptor.
- 2006
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 101:1, s. 28-39
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. The EGFR is expressed in malignant ovarian tumor tissue, and tissue content of EGFR has been directly associated with poor prognosis in patients with ovarian cancer. The uPA system plays a role in pericellular proteolysis, cell migration, invasion, and is over-expressed in ovarian cancer. This study explored the effects of EGF on uPAR expression in the ovarian cancer cell line OVCAR-3. Methods. We used OVCAR-3 cells and the following methods: cell migration assay, time-lapse video microscopy, real-time PCR, assays for cellular binding of I-125-uPA and cellular degradation of I-125-uPA:PAI-1 complex, biosynthetic labeling using S-35-methionin, Western blot, Northern blot, and ELISAs for uPA, PAI-1, and uPAR. Results. EGF up-regulates both protein and mRNA not only for uPAR, but also for the ligand uPA and its inhibitor PAI-1. Cell surface uPAR, in control as well as EGF-stimulated cells, is present only in the intact, not the cleaved, form. Ligand binding experiments showed an increase of endogenously occupied uPAR, whereas non-occupied receptor sites were not increased. In addition, EGF treatment resulted in decreased degradation of radiolabeled uPA:PAI-1 complex. This suggests decreased internalization of uPAR, since the complex is internalized together with uPAR. Like EGF, colchicine, which inhibits endocytosis, increased cell surface expression of uPAR. In addition, we found an immediate increase of uPAR after exposing the cells to EGF and this was accompanied by a transient increase of cell migration. The increase of cell surface uPAR in response to EGF is accompanied by increased release of the soluble form of uPAR (suPAR) to the medium as well as by increased cell migration. Both uPAR and suPAR increased in cells treated with the endocytosis inhibitor colchicine even though cell migration was inhibited, suggesting that the mechanism of uPAR shedding is not related to cell migration. Conclusion. Increased cell surface uPAR in response to EGF stimulation results from mobilization of uPAR from detergent-resistant domains, increased expression of uPAR mRNA, and decreased internalization and degradation of uPAR. Both the anti-uPAR antibody R3, which inhibits binding of uPA, and the EGFR phosphorylation inhibitor Iressa inhibited cell migration in response to uPA as well as to EGF, suggesting that EGFR and uPAR are engaged in the same multiprotein assembly on the cell surface. (C) 2005 Elsevier Inc. All rights reserved.
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| 5. |
- Malander, Susanne, et al.
(författare)
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The contribution of the hereditary nonpolyposis colorectal cancer syndrome to the development of ovarian cancer.
- 2006
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 101:2, s. 238-243
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Ovarian cancer has one of the highest fractions of hereditary cases. The hereditary breast and ovarian cancer syndrome, primarily due to mutations in BRCA1 and BRCA2, is the main cause of heredity, but also the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome confers an increased risk of ovarian cancer. In order to clarify the contribution of HNPCC to the development of ovarian cancer, we collected data on family history of cancer and characterized MMR function in a consecutive series of 128 tumors unselected for age at diagnosis and previously characterized for BRCA gene mutations. Methods. Expression of the MMR proteins MLH1 PMS2, MSH2, and MSH6 was analyzed by immunohistochemistry using tissue microarray sections. Tumors with reduced staining or loss of staining were also analyzed for microsatellite instability (MSI). Results. Loss of MMR protein expression was identified in 3 ovarian cancers, all of which had a MSI-high phenotype. DNA sequence analysis revealed disease-causing germline mutations (deletions of exons 4-6 in MLHI and a 1-nucleotide deletion in exon 5 of MSH6) in two patients diagnosed at ages 40 and 49 years, both of whom had family histories suggestive of HNPCC. The genetic defect in the third case, which was a 47-year old woman without knowledge about her family history with loss of MLH1/PMS2 expression in the tumor tissue, remains elusive. A family history suggestive of HNPCC was identified in an additional case, but this tumor showed normal, retained MMR protein expression and a microsatellite stable phenotype. Conclusions. About 2% of ovarian cancer is caused by germline mutations in the MMR-genes, a minor proportion as compared to the contribution of the BRCA-genes (11% in the present series). However, identification of HNPCC patients is important since it allows inclusion of high-risk individuals into control programs aimed at preventing the more frequent colorectal and endometrial cancers. Tumors within the HNPCC-spectrum should therefore be included when recording a family history of cancer among patients diagnosed with ovarian cancer. (c) 2005 Elsevier Inc. All rights reserved.
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| 6. |
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| 7. |
- Persson, Jan, et al.
(författare)
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Robot-assisted abdominal laparoscopic radical trachelectomy.
- 2008
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 111, s. 564-567
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Radical trachelectomy in conjunction with pelvic lymphadenectomy is an established method to preserve fertility in early cases of cervical cancer. The radical trachelectomy is usually performed vaginally despite the initial use of laparoscopy for the lymphadenectomy. The complexity of a laparoscopic abdominal trachelectomy may explain this dual approach. Here we describe the surgical technique of a robot-assisted laparoscopic radical trachelectomy with lymphatic mapping using a radiotracer and without a vaginal approach. CASES AND SURGICAL TECHNIQUE: Two nulliparous women with early cervical cancer underwent a laparoscopic radical trachelectomy and pelvic lymphadenectomy with the assistance of the da Vinci robot (Intuitive Surgical Inc, Sunnyvale, CA). After the sentinel lymph nodes were found negative on frozen section, the parametria, paracolpia and sacrouterine ligaments were dissected sparing the main branches of the uterine arteries. Following ligation of the descending branches of the uterine arteries the cervix and the vagina were transsected using monopolar diathermia and the vagina was sutured to the remaining cervix. Finally, a permanent cerclage was placed. Time for surgery was 387 and 358 min respectively. No perioperative complications were noted and the postoperative period was uneventful in both cases. CONCLUSIONS: Robot-assisted laparoscopic abdominal trachelectomy is a feasible alternative to a combined laparoscopic and vaginal approach.
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| 8. |
- Persson, Jan, et al.
(författare)
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Robot assisted laparoscopic radical hysterectomy and pelvic lymphadenectomy with short and long term morbidity data.
- 2009
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 113, s. 185-190
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate feasibility and morbidity of robot assisted laparoscopic radical hysterectomy. METHODS: From December 2005 to September 2008 robot assisted laparoscopic radical hysterectomy and pelvic lymphadenectomy was performed on 80 women. Using a prospective protocol, and an active investigation policy for defined adverse events, perioperative, short and long term data were obtained. RESULTS: Time for surgery (skin to skin) reached 176 and 132 min after 9 and 34 procedures respectively. All tumours were radically removed. Median number of retrieved lymph nodes was 26 (range 15-55). All women had an early follow up (1-3 months) and 43 of eligible 46 women (93%) had a long term follow up (>/=12 months). In 33 of 80 women (41%) the peri/postoperative period was uneventful. The remainder had one or more mainly mild adverse events, most commonly from the vaginal cuff (n=17, 21%) or the lymphatic system (n=16, 20%). The proportion of uneventful cases increased significantly over time. Five women were resutured for dehiscence of the vaginal cuff, two women were reoperated for trocar site hernias and one woman had a ureter stricture that resolved following stent treatment. Eight women (14%) needed 60 days or more to resume spontaneous voiding. One 72-year old woman with disseminated endometrial cancer on autopsy died of pulmonary embolism 31 days after surgery. CONCLUSIONS: Robot assisted laparoscopic radical hysterectomy is a feasible alternative to conventional laparoscopy and open surgery. Effort should be made to ensure proper closure of the vaginal cuff, trocar sites and to develop nerve sparing techniques.
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| 9. |
- Skírnisdóttir, Ingiridur, et al.
(författare)
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Non-genital tract metastases to the ovaries presented as ovarian tumors in Sweden 1990-2003 : occurrence, origin and survival compared to ovarian cancer
- 2007
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 105:1, s. 166-171
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this register study was to determine occurrence of non-genital ovarian metastasis detected by gynecologic surgery presented as ovarian neoplasm in Sweden from 1 January 1990 to 31 December 2003. Origin of metastases and time of detection in relation to surgery were recorded. Age at diagnosis, survival for ovarian metastasis compared to ovarian cancer and prognostic factors were evaluated. METHODS: Utilizing the population-based Swedish In-Patient Registry, Cancer Registry and Causes of Death Registry, we identified 255 cases with non-genital tract metastases to the ovaries detected at gynecological surgery. During the study period, 10,955 newly diagnosed cases of ovarian cancer were reported to the Swedish Cancer Registry. RESULTS: The proportion of ovarian metastases detected at surgery of all ovarian neoplasm increased from 1.7% to 3.0% during the study period. The patients with ovarian metastasis of non-GI origin were younger than patients with primary ovarian cancer. The most common primary diseases were breast cancer (29%), colon cancer (27%) and gastric cancer (16%). Ovarian metastasis of GI origin preceded primary diagnosis in 51% of patients but for women with disease of non-GI origin the primary diagnosis was made in 18% of patients after surgery. Five-year survival for patients with ovarian metastasis of GI origin was 11% and it was 24% if metastases were of non-GI origin. Five-year survival for women with ovarian metastases from breast cancer was 26%. In a multivariate analysis, GI surgery at primary surgery for ovarian metastasis was unfavorable prognostic factor. Diagnosis of primary disease known before surgery, primary disease of non-GI or unknown origin and operation at university hospital all had favorable prognostic impact for overall survival. CONCLUSIONS: Detection of non-genital ovarian metastasis at gynecologic surgery is associated with poor prognosis, and prognosis is worse in tumors with GI origin and if the primary is not detected prior to surgery. The results indicate that a thorough patient evaluation is very important before surgery for suspected ovarian neoplasm.
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| 10. |
- Valentin, Lil, et al.
(författare)
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Ultrasound characteristics of different types of adnexal malignancies.
- 2006
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 102:1, s. 41-48
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To describe ultrasound characteristics of adnexal malignancies, i.e., borderline ovarian tumors, primary invasive ovarian epithelial cancer stage 1, primary invasive ovarian epithelial cancer stages 2–4, rare types of malignancy, and metastatic tumors. Methods. In a prospective international study involving nine European ultrasound centers, 1066 women with a pelvic mass judged to be of adnexal origin underwent transvaginal gray scale and color Doppler ultrasound examination by a skilled examiner before surgery. A standardized examination technique and predefined definitions of ultrasound characteristics were used. Results. Of 1066 masses, 266 were malignant and are included: 55 ovarian borderline tumors, 144 primary invasive epithelial ovarian cancers (42 stage 1, 102 stages 2–4), 25 rare malignancies, and 42 metastatic tumors. Most (56%) metastatic tumors and most (60%) rare types of tumor were solid and richly vascularized at color Doppler ultrasound examination (on a scale ranging from 1 to 4, color score based on subjective evaluation was 3 or 4 in 88% and 86%, respectively). Borderline ovarian tumors and stage 1 primary invasive ovarian epithelial cancers differed from stages 2–4 primary invasive ovarian epithelial cancers: they were larger (median volume 375 ml and 695 ml vs. 209 ml; P = 0.0213 and 0.0001), a larger proportion contained papillary projections (64% and 67% vs. 41%; P = 0.0072 and 0.0054), they were more often multilocular cysts without solid components (18% and 14% vs. 2%; P < 0.0017 and 0.0204), but they were less often purely solid (5% and 7% vs. 38%; P ≤ 0.0001 and 0.0005). With increasing degree of invasiveness – from borderline epithelial ovarian tumors via stage 1 invasive epithelial ovarian tumors to stages 2–4 invasive epithelial ovarian tumors – ascites became more common (9% vs. 31% vs. 61%; P = 0.0082, <0.0001, and 0.0017), and, among tumors with solid components (n = 179), the proportion of tumor consisting of solid tissue increased (median 2%–10%–34%; P = 0.0212, <0.0001, and 0.0003). Conclusion. Papillary projections are characteristic of borderline tumors and stage 1 primary invasive epithelial ovarian cancer. A small proportion of solid tissue at ultrasound examination makes a malignant mass more likely to be a borderline tumor or a stage 1 epithelial ovarian cancer than an advanced ovarian cancer, a metastasis, or a rare type of tumor.
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