| 41. |
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| 42. |
- Heitz, F., et al.
(författare)
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Early tumor regrowth is a contributor to impaired survival in patients with completely resected advanced ovarian cancer. An exploratory analysis of the Intergroup trial AGO-OVAR 12
- 2019
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Ingår i: Gynecologic Oncology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0090-8258 .- 1095-6859. ; 152:2, s. 235-242
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Surgical assessment of residual tumor provides the strongest prognostic information in advanced ovarian cancer (AOC), with the best outcome observed after complete resection. Postoperative radiological assessment before initiation of chemotherapy can supplement the information obtained by surgical assessment; however, it may also reveal conflicting findings. Methods. Patients with AOC enrolled in the AGO-OVAR 12 trial underwent baseline imaging before the first chemotherapy cycle. The findings from surgical and radiologic assessment for disease extend were compared. Additionally, an integrated approach was assessed. Results. Complete data from all 3 assessment methods were available for 1345 patients. Of 689 patients with complete resection, tumor was observed in 28% and 22% of patients undergoing radiologic and integrated assessment, respectively. Patients with surgical- radiological and surgical-integrated concordant findings showed a 5-year overall survival (5Y-OS) of 72% and 71%, whereas patients with surgical-radiological and surgical-integrated discordant results showed inferior 5Y-OS of 47% and 49%, respectively. Patients with surgically assessed residual disease had a 5-YOS of 37%. The interval between surgery and baseline assessment was independently associated with discordance between assessment methods, which might reflect early tumor regrowth. Conclusions. Baseline tumor assessment before chemotherapy provides information that stratifies patients with complete resection into different prognostic groups. Integrating the data from different assessment methods might lead to improved definitions of prognostic groups. Further investigation to determine if earlier initiation of chemotherapy after debulking surgery could increase survival of patients with early tumor regrowth is warranted. (C) 2018 Published by Elsevier Inc.
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| 43. |
- 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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| 44. |
- Hellman, K., et al.
(författare)
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Primary treatment and relative survival by stage and age in vulvar squamous cell carcinoma: A population-based SweGCG study
- 2020
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 159:3, s. 663-671
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Vulvar cancer affects mainly elderly women and with an ageing population the incidence has increased. We explored the primary treatment patterns and relative survival of patients with vulvar squamous cell carcinoma (VSCC) by stage and age-group. Methods: A population-based nationwide study on women diagnosed with VSCC between 2012 and 2016 and registered in the Swedish Quality Registry for Gynecologic Cancer (SQRGC). Main outcome was 5-year relative survival (RS) estimated by the Pohar Perme method. The relative risk of excess mortality (EMRR) between different groups was analyzed by Poisson regression. The age-standardized relative survival (AS-RS) was estimated for the total cohort. Results: Median follow-up time was 41 months. The study population included 657 women; 33% were ≥ 80 years old. FIGO stage I was most common (55%). Primary surgery was performed in 96% stage I, 65% stage II, 80% stage III and 28% stage IV. In women ≥80 years, exploration of the groins and chemoradiotherapy was less often performed. They also received lower mean doses of radiation than younger women. The 5-year AS-RS was 74%. 5-year RS was 84% for stage I, 60% for stage II, 54% for stage III and 35% for stage IV. The EMRR for women ≥80 years compared with women <60 years was 4.3 (p < 0.001); 4.9 (p < 0.001) for stages I-II and 3.5(p = 0.007) for stage III. Conclusions: In general, primary treatment of patients with vulvar squamous cell carcinoma in Sweden adhered to guidelines. Areas of improvement include treatment for stage II and for the very old. © 2020 Elsevier Inc.
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| 45. |
- Hemminki, Kari, et al.
(författare)
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Effect of autoimmune diseases on risk and survival in female cancers.
- 2012
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 127:1, s. 180-185
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Patients with autoimmune (AI) diseases are diagnosed with increased frequencies of some cancers, which may depend on the underlying dysregulation of the immune system or treatment. Data on female cancers are limited. METHODS: We analyzed systematically risk and survival of female cancers of the breast, uterus, ovary and other genital organs in close to 200,000 patients diagnosed with any of 33 different AI diseases. Standardized incidence ratios (SIRs) for risk and hazard ratios (HRs) for survival were calculated for subsequent incident cancers or cancer deaths up to year 2008. RESULTS: For all breast cancer after any AI diseases, the SIR was 0.94; SIRs were modestly increased after two AI diseases and decreased after nine AI diseases, including Sjogren syndrome (0.46). For cervical cancer, the risk was increased after discoid lupus erythematosus (3.34) and systemic sclerosis (2.43). The HR was 2.12 in chronic rheumatic heart disease patients. The overall SIR for endometrial cancer was 0.85, with low SIR in ankylosing spondylitis (0.37); the HR was 4.05 for Sjogren syndrome. The SIR for ovarian cancer was increased for polymyositis/dermatomyositis (3.26) while the HR was increased for multiple sclerosis (2.43). The overall SIR for other genital cancers was increased to 1.54 and a very high risk of 35.88 was observed in localized scleroderma. CONCLUSIONS: Breast, endometrial and ovarian cancers were decreased after all AI diseases and most significant changes after individual AI diseases were towards lower risks. Probably treatment related factors explain the findings. For cervical and other genital cancers all significant changes were increased risks.
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| 46. |
- 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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| 47. |
- Herzog, Thomas J., et al.
(författare)
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Correlation between CA-125 serum level and response by RECIST in a phase III recurrent ovarian cancer study
- 2011
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Ingår i: Gynecologic Oncology. - New York : Elsevier BV. - 0090-8258 .- 1095-6859. ; 122:2, s. 350-355
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate in a large phase III recurrent ovarian cancer trial (OVA-301): 1) the concordance between CA-125 level vs. best overall response (OR) and progression-free survival (PFS) determined by radiological assessment 2) the impact of early CA-125 changes over the subsequent radiological response, and 3) the prognostic value of CA-125 response and CA-125 PFS to predict radiological response and PFS. Methods: Assessment of response in the entire randomized population was performed by the Response Evaluation Criteria in Solid Tumors 1.0 (RECIST) and modified Rustin criteria for CA-125 determination. Results: Most CA-125 decreases were observed in RECIST responders (82% of patients treated with the combination and 74% in the PLD alone). CA-125 progression preceded REC1ST progression in 35% of patients with a median lead time of 8.4 weeks. A high concordance rate between CA-125 PFS status at 4 months (PFS4) and CA-125 response as a predictor of PFS4 (87%) and radiological response (79%) was found in the combination, with high positive predictive value for radiological PFS4 (92%) and high negative predictive value for OR (90%). An early CA-125 decrease was predictive for the ultimate response since it was found in a high rate of RECIST responders. Conclusion: Radiological response was preceded by a favorable predictive CA-125 decrease in a high proportion of patients, suggesting that CA-125 evaluation may be an appropriate tool for tumor assessment in patients with ovarian cancer.
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| 48. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 49. |
- Horvath, György, 1942, et al.
(författare)
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Function of the exon 7 deletion variant estrogen receptor alpha protein in an estradiol-resistant, tamoxifen-sensitive human endometrial adenocarcinoma grown in nude mice.
- 2002
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Ingår i: Gynecologic oncology. - : Elsevier BV. - 0090-8258. ; 84:2, s. 271-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In addition to hormone and DNA binding, interactions, including competition with other proteins, appear to be a critical component of transcriptional regulation by the estrogen receptor alpha (ER(alpha)). In vitro studies suggest that exon deletion (Delta exon) variant forms of ER(alpha) may also play an important role in determining the progression from hormone dependence to hormone independence in receptor positive tumors. METHODS: We investigated the presence of ERalpha mRNA and protein variants and their possible role in a moderately differentiated human endometrial adenocarcinoma grown in nude mice. In addition to wild-type (wt), RT-PCR assay of the tumor revealed the presence of two mRNA variants, a low concentration of Delta5 and a high concentration of Delta7 ER(alpha). We detected wt, Delta7, and Delta5,7 mRNA by sequencing the transcripts after stable transfection of three HeLa cells with either splice variant. The linked in vitro translation/transcription assay of the transfected cells and the Western blot analysis of the original tumor generated both wt (66 kDa) and Delta7 (52 kDa), Delta5,7 (46 kDa) ER(alpha) proteins. RESULTS: Tumor growth was characterized as estradiol and progesterone resistant but tamoxifen sensitive, i.e., neither estradiol nor progesterone treatment altered the growth rate, whereas tamoxifen treatment significantly increased the tumor volume doubling time. Estradiol treatment decreased the wt and increased the Delta7 variant ER(alpha) protein expression significantly in a dose-dependent manner. Tamoxifen treatment, however, increased the expression of both proteins whereas progesterone had no effect. Estradiol treatment did not influence expression of the Delta5,7 variant protein, which increased significantly in the tamoxifen-treated tumors. Gel mobility shift assays revealed that both wt and Delta7 ER(alpha) proteins bind to the consensus DNA sequence, whereas the Delta5,7 variant protein did not. CONCLUSIONS: We conclude that estradiol, tamoxifen, and progesterone regulate wt and variant ER(alpha) mRNA and protein expression separately and differently and that this hormonal regulation probably occurs, via different mechanisms, at the transcriptional or posttranscriptional level. The Delta7 variant ER(alpha) may play a crucial role in the determination of hormone sensitivity and thus in the outcome of hormone treatment of human endometrial adenocarcinomas.
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| 50. |
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