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  • 1.
    Carlsson, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy.
    Strang, Peter
    Facts, misconceptions, and myths about cancer.: What do patients with gynecological cancer and the female public at large know?1997In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 65, p. 46-53Article in journal (Refereed)
  • 2.
    Dahm-Kahler, Pernilla
    et al.
    Sahlgrens Univ Hosp, Dept Obstet & Gynecol, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Gothenburg, Sweden..
    Borgfeldt, Christer
    Lund Univ, Skane Univ Hosp, Dept Obstet & Gynecol, Lund, Sweden..
    Holmberg, Erik
    Sahlgrens Univ Hosp, Reg Canc Ctr Western Sweden, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Gothenburg, Sweden..
    Staf, Christian
    Sahlgrens Univ Hosp, Reg Canc Ctr Western Sweden, Gothenburg, Sweden..
    Falconer, Henrik
    Karolinska Univ Hosp, Div Obstet & Gynecol, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Bjurberg, Maria
    Skane Univ Hosp, Dept Clin Sci, Lund, Sweden..
    Kjolhede, Preben
    Linkoping Univ, Dept Clin & Expt Med, Dept Obstet & Gynecol, Linkoping, Sweden..
    Rosenberg, Per
    Linkoping Univ Hosp, Dept Oncol, Linkoping, Sweden..
    Stålberg, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hogberg, Thomas
    Lund Univ, Dept Canc Epidemiol, Lund, Sweden..
    Avall-Lundqvist, Elisabeth
    Linkoping Univ, Dept Oncol, Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.;Karolinska Inst, Dept Pathol & Oncol, Stockholm, Sweden..
    Population-based study of survival for women with serous cancer of the ovary, fallopian tube, peritoneum or undesignated origin - on behalf of the Swedish gynecological cancer group (SweGCG)2017In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 144, no 1, p. 167-173Article in journal (Refereed)
    Abstract [en]

    Objective. The aim of the study was to determine survival outcome in patients with serous cancer in the ovary, fallopian tube, peritoneum and of undesignated origin. Methods. Nation-wide population-based study of women 18 years with histologically verified non-uterine serous cancer, included in the Swedish Quality Registry for primary cancer of the ovary, fallopian tube and peritoneum diagnosed 2009-2013. Relative survival (RS) was estimated using the Ederer II method. Simple and multivariable analyses were estimated by Poisson regression models. Results. Of 5627 women identified, 1246 (22%) had borderline tumors and 4381 had malignant tumors. In total, 2359 women had serous cancer; 71% originated in the ovary (OC), 9% in the fallopian tube (FTC), 9% in the peritoneum (PPC) and 11% at an undesignated primary site (UPS). Estimated RS at 5-years was 37%; for FTC 54%, 40% for OC, 34% for PPC and 13% for UPS. In multivariable regression analyses restricted to women who had undergone primary or interval debulldng surgery for OC, FTC and PPC, site of origin was not independently associated with survival. Significant associations with worse survival were found for advanced stages (RR 2.63, P<0.001), moderate (RR 1.90, P<0.047) and poor differentiation (RR 2.20, P<0.009), neoadjuvant chemotherapy (RR1.33, P<0.022), residual tumor (RR 2.65, P<0.001) and platinum single (2.34, P<0.001) compared to platinum combination chemotherapy. Conclusion. Survival was poorer for serous cancer at UPS than for ovarian, fallopian tube and peritoneal cancer. Serous cancer at UPS needs to be addressed when reporting and comparing survival rates of ovarian cancer.

  • 3.
    Edqvist, Per-Henrik D.
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Huvila, Jutta
    Forsstrom, Bjorn
    Talve, Lauri
    Carpen, Olli
    Salvesen, Helga B.
    Krakstad, Camilla
    Grenman, Seija
    Johannesson, Henrik
    Ljungqvist, Oscar
    Uhlen, Mathias
    Ponten, Fredrik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Auranen, Annika
    Loss of ASRGL1 expression is an independent biomarker for disease-specific survival in endometrioid endometrial carcinoma2015In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 137, no 3, p. 529-537Article in journal (Refereed)
    Abstract [en]

    Objective. For endometrial carcinoma, prognostic stratification methods do not satisfactorily identify patients with adverse outcome. Currently, histology, tumor grade and stage are used to tailoring surgical treatment and to determine the need for adjuvant treatment Low-risk patients are not considered to require adjuvant therapy or staging lymphadenectomy. For patients with intermediate or high risk, some guidelines recommend tailoring adjuvant treatment according to additional negative prognostic factors. Our objective was to evaluate the biomarker potential of the ASRGL1 protein in endometrial carcinoma. Methods. Using The Human Protein Atlas (www.proteinatlas.org), the L-asparaginase (ASRGL1) protein was identified as an endometrial carcinoma biomarker candidate. ASRGL1 expression was immunohistochemically evaluated with an extensively validated antibody on two independent endometrial carcinoma cohorts (n = 229 and n = 286) arranged as tissue microarrays. Staining results were correlated with clinical features. Results. Reduced expression of ASRGL1, defined as <75% positively stained tumor cells, was significantly associated with poor prognosis and reduced disease-specific survival in endometrioid endometrial adenocarcinoma (EEA). In multivariate analysis the hazard ratios for disease-specific survival were 3.55 (95% CI = 1.10-11.43; p = 0.003) and 323 (95% Cl = 1.53-6.81; p = 0.002) in the two cohorts, respectively. Of the 48 cases with Grade 3 Stage I tumor all disease-related deaths were associated with low ASRGL1 expression. Conclusions. Loss of ASRGL1 in EEA is a powerful biomarker for poor prognosis and retained ASRGL1 has a positive impact on survival. ASRGL1 immunohistochemistry has potential to become an additional tool for prognostication in cases where tailoring adjuvant treatment according to additional prognostic factors besides grade and stage is recommended.

  • 4.
    Fonnes, Tina
    et al.
    Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen; Haukeland Hosp, Dept Obstet & Gynecol, Bergen.
    Berg, Hege F.
    Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen; Haukeland Hosp, Dept Obstet & Gynecol, Bergen.
    Bredholt, Therese
    Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen; Haukeland Hosp, Dept Obstet & Gynecol, Bergen.
    Edqvist, Per-Henrik D.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sortland, Kristina
    Univ Bergen, Dept Biomed, Bergen.
    Berg, Anna
    Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen; Haukeland Hosp, Dept Obstet & Gynecol, Bergen.
    Salvesen, Helga B.
    Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen; Haukeland Hosp, Dept Obstet & Gynecol, Bergen.
    Akslen, Lars A.
    Haukeland Hosp, Dept Pathol, Bergen; Univ Bergen, Ctr Canc Biomarkers, Dept Clin Med, Sect Pathol, Bergen.
    Werner, Henrica M. J.
    Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen; Haukeland Hosp, Dept Obstet & Gynecol, Bergen.
    Trovik, Jone
    Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen; Haukeland Hosp, Dept Obstet & Gynecol, Bergen.
    Tangen, Ingvild L.
    Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen; Haukeland Hosp, Dept Obstet & Gynecol, Bergen.
    Krakstad, Camilla
    Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen; Haukeland Hosp, Dept Obstet & Gynecol, Bergen.
    Asparaginase-like protein 1 is an independent prognostic marker in primary endometrial cancer, and is frequently lost in metastatic lesions2018In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 148, no 1, p. 197-203Article in journal (Refereed)
    Abstract [en]

    Objective

    Loss of Asparaginase-like protein 1 (ASRGL1) has been suggested as a prognostic biomarker in endometrial carcinoma. Our objective was to validate this in a prospectively collected, independent patient cohort, and evaluate ASRGL1 expression in endometrial carcinoma precursor lesion and metastases.

    Methods

    782 primary endometrial carcinomas, 90 precursor lesions (complex atypical hyperplasia), and 179 metastases (from 87 patients) were evaluated for ASRGL1 expression by immunohistochemistry in relation to clinical and histopathological data. ASRGL1 mRNA level was investigated in 237 primary tumors and related to survival and ASRGL1 protein expression.

    Results

    Low expression of ASRGL1 protein and ASRGL1 mRNA predicted poor disease specific survival (P < 0.001). In multivariate survival analyses ASRGL1 had independent prognostic value both in the whole patient cohort (Hazard ratio (HR): 1.53, 95% confidence interval (CI): 1.04–2.26, P = 0.031) and within the endometrioid subgroup (HR: 2.64, CI: 1.47–4.74, P = 0.001). Low ASRGL1 expression was less frequent in patients with low grade endometrioid primary tumors compared to high grade endometrioid and non-endometrioid primary tumors, and ASRGL1 was lost in the majority of metastatic lesions.

    Conclusions

    In a prospective setting ASRGL1 validates as a strong prognostic biomarker in endometrial carcinoma. Loss of ASRGL1 is associated with aggressive disease and poor survival, and is demonstrated for the first time to have independent prognostic value in the entire endometrial carcinoma patient population.

  • 5.
    Gyllensten, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Gustavsson, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lindell, Monica
    Wilander, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Primary high-risk HPV screening for cervical cancer in post-menopausal women2012In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 125, no 2, p. 343-345Article in journal (Refereed)
    Abstract [en]

    Objective. The present study was conducted to examine the value of screening for high-risk HPV in post-menopausal women.

    Methods. A cohort of post-menopausal women (n =2113), age range 55-76 years, from Uppsala County, Sweden, were offered testing for both high-risk HPV and a Pap smear in the gynaecological screening during 2008-2010. For the HPV test the cervical smear sample was applied to a filter paper matrix, an indicating FTA elute card and HPV typing performed using a real-time PCR assay. Histological verified CIN2+ lesion was used as an end-point measurement.

    Results. High-risk HPV were found in 6.2% (95% CI 5.2-7.3%) of the women (n = 130) and 22% (95% CI 14-32%) (n = 17) of these had CIN2 + lesions based on histology. The Pap smear taken in conjunction with the HPV test was abnormal in 9.7% (95% CI 5.7-16.3%) (n = 12) of HPV positive women. Among HPV positive women with an abnormal Pap smear, the frequency of histology verified CIN2+ lesions was 67% (95% Cl 38-86%) (n = 8), as compared to 14% (95% CI 7-24%) (n = 9) in HPV positive women with a normal smear. The prevalence of HPV16 in CIN2+ lesions (29%, 95% CI 22-37%) in post-menopausal women was less than half of previous estimates in pre-menopausal women from this population.

    Conclusions. Most histological CIN2+ lesions in post-menopausal women are not recognized by a single Pap smear. A large fraction of pre-invasive cervical cancer cases in post-menopausal women result from infections by HPV types not included in the present vaccine formulas.

  • 6.
    Hellberg, Dan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Tot, Tibor
    Dept of Pathology and Clincal Cytology, Falun Central Hospital, Falun Sweden.
    Stendahl, Ulf
    Pitfalls in immunohistochemical validation of tumor marker expression: exemplified in invasive cancer of the uterine cervix2009In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 112, no 1, p. 235-240Article in journal (Refereed)
    Abstract [en]

    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.

  • 7.
    Huvila, Jutta
    et al.
    Univ Turku, Turku Univ Hosp, Dept Pathol, Pl 52, FIN-20520 Turku, Finland.
    Laajala, Teemu D.
    Univ Turku, Dept Math & Stat, Pl20, Helsinki 00014, Finland;Univ Helsinki, FIMM, Inst Mol Med Finland, Pl20, FIN-00014 Helsinki, Finland.
    Edqvist, Per-Henrik D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mardinoglu, Adil
    KTH Royal Inst Technol, Sci Life Lab, S-10044 Stockholm, Sweden;Chalmers Univ Technol, Dept Biol & Biol Engn, S-41296 Gothenburg, Sweden.
    Talve, Lauri
    Univ Turku, Turku Univ Hosp, Dept Pathol, Pl 52, FIN-20520 Turku, Finland.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Grenman, Seija
    Univ Turku, Turku Univ Hosp, Dept Gynaecol & Obstet, Pl52, FIN-20520 Turku, Finland.
    Carpen, Olli
    Univ Turku, Turku Univ Hosp, Dept Pathol, Pl 52, FIN-20520 Turku, Finland;Univ Helsinki, Dept Pathol, Helsinki, Finland;Finland HUSIAB, Pl720, Helsinki 00029, Finland.
    Aittokallio, Tero
    Univ Turku, Dept Math & Stat, Pl20, Helsinki 00014, Finland;Univ Helsinki, FIMM, Inst Mol Med Finland, Pl20, FIN-00014 Helsinki, Finland.
    Auranen, Annika
    Univ Tampere, Tampere Univ Hosp, Dept Gynaecol & Obstet, Pl2000, Tampere 33521, Finland.
    Combined ASRGL1 and p53 immunohistochemistry as an independent predictor of survival in endometrioid endometrial carcinoma2018In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 149, no 1, p. 173-180Article in journal (Refereed)
    Abstract [en]

    Objective. In clinical practise, prognostication of endometrial cancer is based on clinicopathological risk factors. The use of immunohistochemistry-based markers as prognostic tools is generally not recommended and a systematic analysis of their utility as a panel is lacking. We evaluated whether an immunohistochemical marker panel could reliably assess endometrioid endometrial cancer (EEC) outcome independent of clinicopathological information. Methods. A cohort of 306 EEC specimens was profiled using tissue microarray (TMA). Cost- and time-efficient immunohistochemical analysis of well-established tissue biomarkers (ER, PR, HER2, Ki-67, MLH1 and p53) and two new biomarkers (L1CAM and ASRGL1) was carried out. Statistical modelling with embedded variable selection was applied on the staining results to identify minimal prognostic panels with maximal prognostic accuracy without compromising generalizability. Results. A panel including p53 and ASRGL1 immunohistochemistry was identified as the most accurate predictor of relapse-free and disease-specific survival. Within this panel, patients were allocated into high- (5.9%), intermediate- (295%) and low- (64.6%) risk groups where high-risk patients had a 30-fold risk (P < 0.001) of dying of EEC compared to the low-risk group. Conclusions. P53 and ASRGL1 immunoprofiling stratifies EEC patients into three risk groups with significantly different outcomes. This simple and easily applicable panel could provide a useful tool in EEC risk stratification and guiding the allocation of treatment modalities.

  • 8. Huvila, Jutta
    et al.
    Talve, Lauri
    Carpen, Olli
    Edqvist, Per-Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Grenman, Seija
    Auranen, Annika
    Progesterone receptor negativity is an independent risk factor for relapse in patients with early stage endometrioid endometrial adenocarcinoma2013In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 130, no 3, p. 463-469Article in journal (Refereed)
    Abstract [en]

    Objective. In endometrioid endometrial adenocarcinoma (EEA), the currently established prognostic factors in clinical guidelines are stage and grade. Many guidelines include lymphovascular invasion (LVI) and tumor size as prognostic factors. Although several studies have associated lack of estrogen (ER) and progesterone receptor (PR) expression with reduced outcome, the prognostic use of these markers is uncommon. Better prognostication of clinical behavior would be useful in patients with early stage (I-II) disease. In this study we evaluated ER and PR as prognostic factors in EEA, and compared their expression with other potential biomarkers and clinical parameters. Methods. Tissue microarrays were constructed from 182 patients with stages I-II EEA. ER, PR, p53, Ki-67, PTEN, MLH and HER-2 expression were assessed by immunohistochemical staining and HER-2 was confirrried with SISH. The results were correlated with clinicopathologic parameters and to disease-free survival. Results. Eleven patients (6%) developed recurrent disease during a median follow up time of 62.8 months. In univariate analysis FIGO grade (p = 0.019), positive expression of p53 (p = 0.010) and negative PR expression (p = 0.001) were associated with a shorter disease-free survival. In multivariate analysis only negative PR expression (p = 0.019) was significantly associated with a shorter disease-free survival. LVI and tumor size where not of prognostic value. Conclusions. Lack of PR expression is a strong, independent risk factor for tumor recurrence in patients with stages I-II endometrioid endometrial cancer. The use of this easily measurable biomarker as a prognostic factor in the clinical context should be considered and tested in a larger patient population. 

  • 9.
    Ivansson, Emma L.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Juko-Pecirep, Ivana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Gyllensten, Ulf B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Interaction of immunological genes on chromosome 2q33 and IFNG in susceptibility to cervical cancer2010In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 116, no 3, p. 544-548Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Cervical cancer is caused by persistent infection with human papillomavirus and genetic susceptibility factors may augment disease risk. The immune response consists of complex interactions and it was recently proposed that the association of combinations of genotypes at several genes should be examined. In support of this the combination CD28+17(TT)/IFNG+874(AA) was shown to increase cervical cancer risk in a Brazilian population (VB Guzman et al. New approach reveals CD28 and IFNG gene interaction in the susceptibility to cervical cancer. Hum Mol Genet 2008;17:1838-44) and our aim was to replicate this finding. METHODS: We re-examined the proposed associations by analysis of polymorphisms at CD28, IFNG, TNF, PDCD1, ICOS and CTLA4 in 1306 Swedish cases and 811 controls. RESULTS: Logistic regression analysis detected association at single SNP level for CD28+17 (p=0.01), IFNG+874 (p=0.02), and PDCD1+7785 (p=0.04). The two locus combination CD28+17(TT)/IFNG+874(AA) (OR=0.76 (0.60-0.96, empirical p=0.03) and the three-locus combination CD28+17(TT)/IFNG+874(AA)/ICOS+1564(TT) (OR=0.65(0.49-0.87), empirical p=0.006) were associated with decreased risk. The strongest association was detected for the combination CTLA4-319 (CC)/IFNG (AA) (OR=0.67(0.53-0.84), empirical p=0.0007). CONCLUSION: The observation that these combinations of loci are associated in different populations supports their importance in cervical cancer development although the opposite directions of the effect call for clarification. The polymorphisms studied might not be the functional variants per se, but linked to those exerting a functional effect. The opposite associations in the two populations could then be explained by differences in linkage disequilibrium and population structure.

  • 10.
    Juko-Pecirep, Ivana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Ivansson, Emma L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Gyllensten, Ulf B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Evaluation of Fanconi anaemia genes FANCA, FANCC and FANCL in cervical cancer susceptibility2011In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 122, no 2, p. 377-381Article in journal (Refereed)
    Abstract [en]

    Objective. Disrupting the function of any of the 13 Fanconi anaemia (FA) genes causes a DNA repair deficiency disorder, with patients being susceptible to a number of cancer types. Variation in the family of FA genes has been suggested to affect risk of cervical cancer. The current study evaluates the influence of three genes in the FA pathway on cervical cancer risk in Swedish women. Methods. TagSNPs in FANCA, FANCC and FANCL were selected using the Tagger algorithm in Haploview. A total of 81 tagSNPs were genotyped in 782 cases (CIN3 or ICC) and 775 controls using the Illumina GoldenGate Assay and statistically analyzed for association with cervical cancer. Results. 72 SNPs were successfully genotyped in >98% of the samples. Nominal associations were detected for FANCA rs11649196 (p = 0.05) and rs4128763 in FANCC (p = 0.02). The associations did not withstand correction for multiple testing. Conclusions. The current study does not support that genetic variation in FANCA, FANCC or FANCL genes affects susceptibility to cervical cancer in the Swedish population.

  • 11.
    Lindström, Annika K
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Asplund, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Correlation between LRIG1 and LRIG2 expressions and expression of 11 tumor markers, with special reference to tumor suppressors, in CIN and normal cervical epithelium2011In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 122, no 2, p. 372-376Article in journal (Refereed)
    Abstract [en]

    Objective. Novel biological markers LRIG1 and LRIG2 have been associated with favorable as well as poor prognosis, respectively, in different cancer types, including cervical cancer. The aim of this study was to investigate possible interactions between these proteins and other tumor markers, and as diagnostic adjuncts in CIN. Methods. Cervical biopsies from 171 women, with normal epithelium, and low-grade and high-grade CIN were stained for LRIG1 and LRIG2, and 11 additional tumor markers. The tumor markers were chosen to be relevant in cervical neoplasms. Staining was evaluated semiquantitatively. Results. Expression of LRIG1 and LRIG2 was found to correlate with increasing CIN grade, as well as with expression of tumor suppressor FHIT, independent of histological grade. In addition, tumor promoter LRIG2 expression correlated negatively with expression of tumor suppressor retinoblastoma protein and positively with IL-10. The latter correlation did not however remain after adjustment for CIN grade. p53 and p16 expressions correlated positively with LRIG1 expression in univariate analyses, but significance did not hold after adjustment for CIN grade. Conclusion. LRIG1 and LRIG2 expressions were seen in precancerous cervical epithelium and found to increase with increasing grade. There was an association between expression of these glycoproteins and FHIT tumor suppressor protein, independently of histological grade.

  • 12.
    Mattsson, Elisabet
    et al.
    Department of Health Care Sciences, Ersta Sköndal Bräcke University College, Stockholm, Sweden.
    Einhorn, Kim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Ljungman, Lisa
    Division of Nursing, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Stålberg, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikman, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Women treated for gynaecological cancer during young adulthood: A mixed-methods study of perceived psychological distress and experiences of support from health care following end-of-treatment2018In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 149, no 3, p. 464-469Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To investigate the prevalence and predictors of cancer-related distress in younger women treated for gynaecological cancer, and to explore women's needs and experiences of psychosocial support following end-of-treatment.

    METHODS:

    Data were collected from 337 gynaecological cancer survivors, 19-39years at diagnosis, using a study-specific questionnaire and the Swedish Quality Register of Gynaecologic Cancer. Predictors of distress were investigated with multivariable logistic regression analysis. Open-ended questions were analysed with content analysis.

    RESULTS:

    The prevalence of cancer-related distress was 85% (n=286) including fear of cancer-recurrence (n=175, 61%), anxiety (n=152, 53%), depression (n=145, 51%), fear of death (n=91, 32%), concerns regarding sexuality (n=87, 34%) and fertility (n=78, 27%), and changed body image (n=78, 27%). Multi-modal treatment (OR 2.25, 95% CI 1.13-4.49) and a history of psychological distress (OR 3.44, 95% CI 1.41-8.39) predicted cancer-related distress. The majority of women experiencing distress also reported a need for support after end-of-treatment (n=205, 71%). One-third of those receiving support reported the received support as inadequate (n=55, 34%). Eight categories described reasons for not seeking support, e.g., lacked strength to seek professional support and too busy managing every-day life and, wanted help but did not know who to turn to. Four categories described reasons for not receiving sought support e.g., found it difficult to openly express feelings, psychosocial care was under-dimensioned, insufficient and unprofessional.

    CONCLUSION:

    Results identify the importance of support and longer-term follow-up for young survivors of gynaecological cancer. The support needs to be organised to meet this group's specific needs.

  • 13.
    Skírnisdóttir, Ingiridur
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Non-genital tract metastases to the ovaries presented as ovarian tumors in Sweden 1990-2003: occurrence, origin and survival compared to ovarian cancer2007In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 105, no 1, p. 166-171Article in journal (Refereed)
    Abstract [en]

    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.

  • 14.
    Stålberg, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Svensson, T.
    Lonn, S.
    Kieler, H.
    The influence of comorbidity on mortality in ovarian cancer patients2014In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 133, no 2, p. 298-303Article in journal (Refereed)
    Abstract [en]

    Background. Ovarian cancer is a severe disease with a peak incidence in the older age groups where concurrent morbidity is common and could potentially influence mortality rates. Objectives. The aim was to study the influence of common comorbidity diagnoses on mortality in ovarian cancer patients. Methods. The study population was patients with ovarian cancer in Sweden 1993-2006 (n = 11.139) identified in the national Cancer Register. Comorbidity data was obtained from the Patient Register and mortality from Cause of Death Register. Mortality was analyzed with Cox' proportional hazards models and subgroup analyses were performed by age and tumor histology. Results. Almost all of the assessed comprbidities increased mortality in ovarian cancer patients. Thromboembolism was the most hazardous comorbidity (HR = 1.95, <1 year after cancer diagnosis and HR = 7.83, 1-5 years after cancer diagnosis) followed by hematologic complications (HR = 1.84 and 7.11 respectively) and infectious disease (HR = 1.48 and 5.28 respectively). The occurrence of diabetes mellitus and hypertension had less impact on mortality. Conclusion. Thromboembolism, hematologic complications and infections had a pronounced effect on mortality rates in women with ovarian cancer. The impact of comorbidity was mainly apparent among those with a more prosperous prognosis, such as longer time since cancer diagnosis, less aggressive tumors and younger age. (C) 2014 Elsevier Inc. All rights reserved.

  • 15.
    Tzortzatos, Gerasimos
    et al.
    Karolinska Inst, Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Div Obstet & Gynecol, S-17176 Solna, Sweden..
    Andersson, Emil
    Karolinska Inst, Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Div Obstet & Gynecol, S-17176 Solna, Sweden..
    Soller, Maria
    Skane Univ Hosp, Dept Clin Genet, S-21428 Malmo, Sweden..
    Askmalm, Marie Stenmark
    Linkoping Univ, Dept Clin Pathol & Clin Genet, Fac Hlth Sci, Cty Council Ostergotland, S-58185 Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Cty Council Ostergotland, Fac Hlth Sci, S-58185 Linkoping, Sweden..
    Zagoras, Theofanis
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Clin Genet,Inst Biomed, S-41345 Gothenburg, Sweden..
    Georgii-Hemming, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Lindblom, Annika
    Karolinska Inst, Karolinska Univ Hosp, Dept Clin Genet, S-17176 Solna, Sweden.;Karolinska Inst, Dept Mol Med & Surg, S-17176 Solna, Sweden..
    Tham, Emma
    Karolinska Inst, Karolinska Univ Hosp, Dept Clin Genet, S-17176 Solna, Sweden.;Karolinska Inst, Dept Mol Med & Surg, S-17176 Solna, Sweden..
    Mints, Miriam
    Karolinska Inst, Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Div Obstet & Gynecol, S-17176 Solna, Sweden..
    The gynecological surveillance of women with Lynch Syndrome in Sweden2015In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 138, no 3, p. 717-722Article in journal (Refereed)
    Abstract [en]

    Objective. Women with Lynch syndrome (LS) have up to a 60% lifetime risk of endometrial cancer (EC) and up to a 24% risk of ovarian cancer (OC). Gynecological surveillance is recommended, but the benefit and how it should be performed remain unclear. The purpose of this study was to assess diagnostic modalities for gynecological screening of LS patients in Sweden and clinical outcome. Methods. A retrospective nationwide study of 170 women with molecularly confirmed LS. Data including gynecological LS screening history, biopsy results (if any), genetic records, number of screening visits, results from screening including transvaginal ultrasound (TVUS), endometrial biopsy (EB), blood test for tumor marker cancer antigen (CA) 125, prophylactic surgery including age at procedure, and setting from which screening data were obtained from medical records. Results. A total of 117 women were eligible for gynecological screening and of these, 86 patients attended screening visits. Of these, 41 underwent prophylactic hysterectomy and/or bilateral salpingo-oophorectomy. Two patients (4.9%) were diagnosed with EC and two (4.9%) with precancerous lesions in conjunction with prophylactic surgery. Total incidence of gynecological cancer in the surveillance group (45 women) was 20% EC, 4% OC. Five patients had endometrial cancer or complex hyperplasia with atypia (n = 2) detected by endometrial biopsy. Four additional cases were detected due to interval bleeding. Both cases of ovarian cancer were detected by transvaginal ultrasound in patients with ovarian cysts under surveillance. The youngest woman with endometrial cancer was diagnosed at 35 years of age, before she was aware of her diagnosis of Lynch syndrome. Conclusions. Gynecological surveillance of women with Lynch syndrome may lead to earlier detection of precancerous lesions, which might have some impact on the morbidity from endometrial cancer although further studies are needed to prove this. Prophylactic hysterectomy with or without bilateral salpingo-oophorectomy reduces the cancer incidence. A practical approach to surveillance in Lynch syndrome women would be to offer annual surveillance beginning at age 30 years including probably both TVUS and EB in order to increase diagnostic yield with prospective data registry for follow-up studies. Prophylactic surgery could be performed at a suitable age after childbearing to obtain a balance between reducing the risk of cancer and minimizing long-term complications from premature menopause. (C) 2015 Elsevier Inc. All rights reserved.

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