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  1. AU="Annukka Pasanen"
  2. AU="Yi, Ling Ka"
  3. AU="Kong, Hyejin"
  4. AU="Bilio, João"
  5. AU=Hill Stephen J
  6. AU="Hatayama, Sho"
  7. AU="Ruuskanen, Suvi K"
  8. AU="Kim, Song-Rae"
  9. AU="Mizia-Stec, Katarzyna"
  10. AU="Helen V. Firth"
  11. AU=Giroux Leprieur Etienne
  12. AU="Xinhui Gao"
  13. AU="Christoph Schlapbach"
  14. AU="Akbar, Shayista"
  15. AU="Butler, Eboneé N"
  16. AU="Moura-Alves, Márcio"
  17. AU="Marcet, Ismael"
  18. AU=Eichfelder Sebastian
  19. AU=Timins M E
  20. AU="Weber, Stephan"
  21. AU=Galuska David
  22. AU="Carrieri, Mariella"
  23. AU="Hafkamp, Frederique J"
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  1. Article ; Online: Differential impact of clinicopathological risk factors within the 2 largest ProMisE molecular subgroups of endometrial carcinoma.

    Annukka Pasanen / Mikko Loukovaara / Terhi Ahvenainen / Pia Vahteristo / Ralf Bützow

    PLoS ONE, Vol 16, Iss 9, p e

    2021  Volume 0253472

    Abstract: Objective To assess whether the prognostic impact of conventional risk factors and ancillary biomarkers differs across the 2 largest ProMisE molecular subgroups of endometrial carcinoma (EC). Methods Direct sequencing of POLE exonuclease domain hot spots ...

    Abstract Objective To assess whether the prognostic impact of conventional risk factors and ancillary biomarkers differs across the 2 largest ProMisE molecular subgroups of endometrial carcinoma (EC). Methods Direct sequencing of POLE exonuclease domain hot spots and immunohistochemistry for MLH1, PMS2, MSH2, MSH6 and p53 were performed on 745 unselected endometrioid ECs to identify mismatch repair deficient (MMR-D, n = 264) and no specific molecular profile (NSMP, n = 206) ECs. Molecular group-specific survival analyses and interaction analyses were performed to determine the prognostic relevance of clinicopathological factors and various biomarkers (L1 cell adhesion molecule, estrogen and progesterone receptor, beta-catenin, p16, E-cadherin, KRAS) within the subgroups. Results Molecular subgroup did not have an independent effect on disease-specific survival after adjustment for conventional risk factors (P = 0.101). High grade (G3) and p16 hyperexpression remained significant predictors of survival in NSMP. Stage II-IV, ≥50% myometrial invasion, lymphovascular space invasion and loss of E-cadherin were independent predictors in the MMR-D group. In the interaction analysis, molecular subclass significantly modified the prognostic effect of high grade and p16 hyperexpression, which showed a stronger negative effect on survival in NSMP as compared to MMR-D (P for interaction = 0.016 for grade and 0.033 for p16). Conclusions Grade of differentiation and p16 hyperexpression appear to have a stronger prognostic impact in NSMP as compared to MMR-D EC. While these results need to be confirmed in a larger study population, they indicate that differential impact of risk factors needs to be taken into account when developing new molecular class-integrated risk stratification algorithms for EC.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Clinical factors as prognostic variables among molecular subgroups of endometrial cancer.

    Anne Kolehmainen / Annukka Pasanen / Taru Tuomi / Riitta Koivisto-Korander / Ralf Bützow / Mikko Loukovaara

    PLoS ONE, Vol 15, Iss 11, p e

    2020  Volume 0242733

    Abstract: Background Clinical factors may influence endometrial cancer survival outcomes. We examined the prognostic significance of age, body mass index (BMI), and type 2 diabetes among molecular subgroups of endometrial cancer. Methods This was a single ... ...

    Abstract Background Clinical factors may influence endometrial cancer survival outcomes. We examined the prognostic significance of age, body mass index (BMI), and type 2 diabetes among molecular subgroups of endometrial cancer. Methods This was a single institution retrospective study of patients who underwent surgery for endometrial carcinoma between January 2007 and December 2012. Tumors were classified into four molecular subgroups by immunohistochemistry of mismatch repair (MMR) proteins and p53, and sequencing of polymerase-ϵ (POLE). Overall, cancer-related, and non-cancer-related mortality were estimated using univariable and multivariable survival analyses. Results Age >65 years was associated with increased mortality rates in the whole cohort (n = 515) and in the "no specific molecular profile" (NSMP) (n = 218) and MMR deficient (MMR-D) (n = 191) subgroups during a median follow-up time of 81 months (range 1‒136). However, hazard ratios for cancer-related mortality were non-significant for NSMP and MMR-D. Diabetes was associated with increased overall and non-cancer-related mortality in the whole cohort and MMR-D subgroup. Overweight/obesity had no effect on outcomes in the whole cohort, but was associated with decreased overall and cancer-related mortality in the NSMP subgroup, and increased overall and non-cancer-related mortality in the MMR-D subgroup. Overweight/obesity effect on cancer-related mortality in the NSMP subgroup remained unchanged after controlling for confounders. High-risk uterine factors were more common, and estrogen and progesterone receptor expression less common in NSMP subtype cancers of normal-weight patients compared with overweight/obese patients. No clinical factors were associated with outcomes in p53 aberrant (n = 69) and POLE mutant (n = 37) subgroups. No cancer-related deaths occurred in the POLE mutant subgroup. Conclusions The prognostic effects of age, BMI, and type 2 diabetes do not appear to be uniform for the molecular subgroups of endometrial cancer. Our data support further evaluation of BMI combined with genomics-based risk-assessment.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616 ; 610
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Parity associates with chromosomal damage in uterine leiomyomas

    Heli Kuisma / Simona Bramante / Kristiina Rajamäki / Lauri J. Sipilä / Eevi Kaasinen / Jaana Kaukomaa / Kimmo Palin / Netta Mäkinen / Jari Sjöberg / Nanna Sarvilinna / Jussi Taipale / Liisa Kauppi / Manuela Tumiati / Antti Hassinen / Janne Pitkäniemi / Jyrki Jalkanen / Sanna Heikkinen / Annukka Pasanen / Oskari Heikinheimo /
    Ralf Bützow / Niko Välimäki / Lauri A. Aaltonen

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 10

    Abstract: Many factors have been associated with chromosomal damage, including mechanical forces in a constrained cellular environment. Here the authors reveal an association between parity and chromosomal damage by analysing karyotypes of 1946 uterine leiomyomas. ...

    Abstract Many factors have been associated with chromosomal damage, including mechanical forces in a constrained cellular environment. Here the authors reveal an association between parity and chromosomal damage by analysing karyotypes of 1946 uterine leiomyomas.
    Keywords Science ; Q
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Multiple clinical characteristics separate MED12-mutation-positive and -negative uterine leiomyomas

    Hanna-Riikka Heinonen / Annukka Pasanen / Oskari Heikinheimo / Tomas Tanskanen / Kimmo Palin / Jaana Tolvanen / Pia Vahteristo / Jari Sjöberg / Esa Pitkänen / Ralf Bützow / Netta Mäkinen / Lauri A. Aaltonen

    Scientific Reports, Vol 7, Iss 1, Pp 1-

    2017  Volume 7

    Abstract: Abstract Up to 86% of uterine leiomyomas harbour somatic mutations in mediator complex subunit 12 (MED12). These mutations have been associated with conventional histology, smaller tumour size, and larger number of tumours within the uterus. Prior ... ...

    Abstract Abstract Up to 86% of uterine leiomyomas harbour somatic mutations in mediator complex subunit 12 (MED12). These mutations have been associated with conventional histology, smaller tumour size, and larger number of tumours within the uterus. Prior studies, with limited sample sizes, have failed to detect associations between other clinical features and MED12 mutations. Here, we prospectively collected 763 uterine leiomyomas and the corresponding normal myometrial tissue from 244 hysterectomy patients, recorded tumour characteristics, collected clinical data from medical records, and screened the tissue samples for MED12 mutations to assess potential associations between clinical variables and mutation status. Out of 763 leiomyomas, 599 (79%) harboured a MED12 mutation. In the analysis of tumour characteristics, positive MED12-mutation status was significantly associated with smaller tumour size, conventional histology, and subserous location, relative to intramural. In the analysis of clinical variables, the number of MED12-mutation-positive tumours showed an inverse association with parity, and the number of mutation-negative tumours showed a positive association with a history of pelvic inflammatory disease. This study confirmed the previously reported differences and discovered novel differentiating features for MED12-mutation-positive and -negative leiomyomas. These findings emphasise the relevance of specific driver mutations in genesis and presentation of uterine leiomyomas.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616 ; 610
    Language English
    Publishing date 2017-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  5. Article ; Online: Genetic predisposition to uterine leiomyoma is determined by loci for genitourinary development and genome stability

    Niko Välimäki / Heli Kuisma / Annukka Pasanen / Oskari Heikinheimo / Jari Sjöberg / Ralf Bützow / Nanna Sarvilinna / Hanna-Riikka Heinonen / Jaana Tolvanen / Simona Bramante / Tomas Tanskanen / Juha Auvinen / Outi Uimari / Amjad Alkodsi / Rainer Lehtonen / Eevi Kaasinen / Kimmo Palin / Lauri A Aaltonen

    eLife, Vol

    2018  Volume 7

    Abstract: Uterine leiomyomas (ULs) are benign tumors that are a major burden to women’s health. A genome-wide association study on 15,453 UL cases and 392,628 controls was performed, followed by replication of the genomic risk in six cohorts. Effects of the risk ... ...

    Abstract Uterine leiomyomas (ULs) are benign tumors that are a major burden to women’s health. A genome-wide association study on 15,453 UL cases and 392,628 controls was performed, followed by replication of the genomic risk in six cohorts. Effects of the risk alleles were evaluated in view of molecular and clinical characteristics. 22 loci displayed a genome-wide significant association. The likely predisposition genes could be grouped to two biological processes. Genes involved in genome stability were represented by TERT, TERC, OBFC1 - highlighting the role of telomere maintenance - TP53 and ATM. Genes involved in genitourinary development, WNT4, WT1, SALL1, MED12, ESR1, GREB1, FOXO1, DMRT1 and uterine stem cell marker antigen CD44, formed another strong subgroup. The combined risk contributed by the 22 loci was associated with MED12 mutation-positive tumors. The findings link genes for uterine development and genetic stability to leiomyomagenesis, and in part explain the more frequent occurrence of UL in women of African origin.
    Keywords uterine leiomyoma ; genome-wide association study ; leiomyomagenesis ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2018-09-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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