Ovarian tumors. Prevalence, malignancy risk and significance of the Plasminogen activation system.
(2001)- Abstract
- The aims were to assess the prevalence of ovarian tumors in fertile asymptomatic women and to evaluate the risk of ovarian cancer in women with a history of benign ovarian tumors and endometriosis. In order to search for biomarkers in ovarian tumors, the plasminogen activating (PA) system was studied.
A random sample of women 25-40 years old was invited to a transvaginal ultrasonography examination. Ovarian cysts were found in 7% (22/335). At follow-up three months later 18 of the 22 cysts had spontaneously disappeared.
In a case-control study, The Swedish Hospital Discharge Register, The National Swedish Cancer Register, and the Fertility Register, were used to analyze the risk of developing ovarian... (More) - The aims were to assess the prevalence of ovarian tumors in fertile asymptomatic women and to evaluate the risk of ovarian cancer in women with a history of benign ovarian tumors and endometriosis. In order to search for biomarkers in ovarian tumors, the plasminogen activating (PA) system was studied.
A random sample of women 25-40 years old was invited to a transvaginal ultrasonography examination. Ovarian cysts were found in 7% (22/335). At follow-up three months later 18 of the 22 cysts had spontaneously disappeared.
In a case-control study, The Swedish Hospital Discharge Register, The National Swedish Cancer Register, and the Fertility Register, were used to analyze the risk of developing ovarian cancer in women hospitalized with the diagnoses of ovarian cyst, functional ovarian cyst, or endometriosis. Young women (15 to 29 years old) discharged from hospital for ovarian cysts and functional cysts showed a doubled risk of developing ovarian cancer. Women with ovarian cysts who had undergone ovarian cyst resection or unilateral oophorectomy had a nine times higher risk of developing ovarian cancer. Women with endometriosis had a minor increased risk of ovarian malignancy. The risk of developing ovarian cancer was inversely related to parity and the mean age at diagnosis of ovarian cancer was lower in all three study groups as compared with the control groups.
The gene expression of urokinase plasminogen activator (uPA), its receptor (uPAR) and inhibitor (PAI-1) was increased in malignant as compared with benign tumors, and also increased in poorly as compared with well-differentiated malignant tumors. All three mRNA species were mainly found in the stroma in poorly differentiated tumors and metastases. Stromal expression may be induced by the tumor cells. The protein levels of uPA, uPAR, uPA:PAI-1 complex were higher in malignant than in benign ovarian tumors. Furthermore, the protein content of uPA, uPA:PAI-1 complex and also PAI-1 was higher in poorly than in well-differentiated tumors. In contrast, the level of uPAR was lower in poorly than in well-differentiated malignant tumors, and also lower in advanced than in early stages of the disease. This discrepancy may be the result of increased turn-over of uPAR in poorly differentiated tumors.
High tumor tissue content of uPAR as well as low content of uPA was associated with longer postoperative survival. (Less) - Abstract (Swedish)
- Popular Abstract in Swedish
Äggstockscystors förekomst, risken för kvinnor med cystor att utveckla äggstockscancer samt Plasminogenaktiveringssystemets uttryck i äggstockstumörer
Äggstockscancer är ovanligt hos unga kvinnor, men den 4:e vanligaste dödsorsaken i cancer hos kvinnor i åldern 45-64 år i Sverige. Livstidsrisken är 1 på 70. På grund av få eller obefintliga symptom upptäcks äggstockscancer sent och ofta när sjukdomen är spridd. Om det ökade användandet av ultraljud lett till tidigare diagnos av äggstockscancer är oklart.
Vi bjöd in ett slumpmässigt urval av kvinnor i 25-40 års ålder till ultraljudsundersökning via slidan, för att få en uppfattning om hur vanligt det är med... (More) - Popular Abstract in Swedish
Äggstockscystors förekomst, risken för kvinnor med cystor att utveckla äggstockscancer samt Plasminogenaktiveringssystemets uttryck i äggstockstumörer
Äggstockscancer är ovanligt hos unga kvinnor, men den 4:e vanligaste dödsorsaken i cancer hos kvinnor i åldern 45-64 år i Sverige. Livstidsrisken är 1 på 70. På grund av få eller obefintliga symptom upptäcks äggstockscancer sent och ofta när sjukdomen är spridd. Om det ökade användandet av ultraljud lett till tidigare diagnos av äggstockscancer är oklart.
Vi bjöd in ett slumpmässigt urval av kvinnor i 25-40 års ålder till ultraljudsundersökning via slidan, för att få en uppfattning om hur vanligt det är med symptomfria cystor på äggstockarna. Vi fann att 6,6 % (22/335) av kvinnorna hade cystor i äggstockarna. Vid uppföljning tre månader senare hade 18 av de 22 cystorna spontant försvunnit.
För att se om kvinnor med äggstockscystor hade ökad risk för äggstockscancer matchades de kvinnor som vårdats för cystor i Sveriges slutenvårdsregister mot tre kontroller via befolkningsregistret. Kvinnor som fått cancer hittades i cancerregistret och antalet födda barn per kvinna via födelseregistret. Yngre kvinnor som sjukhusvårdats för cystor hade en dubblerad risk att senare få äggstockscancer och medelåldern vid cancerdiagnos var sex år lägre. Den ökade risken kvarstod hos kvinnorna trots att cystorna eller äggstocken med cystan opererats bort. Med ökat antal födda barn minskade risken.
För att öka kunskapen om tumörbiologin i äggstockstumörer och eventuellt finna nya tumörmarkörer studerades plasminogenaktiveringssystemet (PA-systemet). PA-systemet är ett proteinsystem som löser upp blodproppar, medverkar i sårläkning och aktiveras vid cancerutveckling vilket medför att omkringliggande vävnad bryts ned och att nya kärl bildas. Vi har i äggstockstumörer studerat genaktiviteterna och proteinmängderna i de olika ingående komponenterna i PA-systemet. Proteinmängderna relaterades även till överlevnad hos 51 cancerpatienter. Vi fann att genaktiviteten ökade för urokinasplasminogenaktivatorn (uPA), dess receptor (uPAR) och hämmare (PAI-1) i mer aggressiva tumörer och dottersvulster. Det var inte cancercellerna som svarade för den ökade genaktiviteten utan bindvävscellerna runt omkring cancercellerna. I tumörvävnad fann vi att proteinmängden ökade av uPA och PAI-1 med ökande aggressivitet i tumörerna. Koncentrationen uPAR var förhöjd i mindre aggressiva jämfört med mer aggressiva cancrar och metastaser. Höga uPAR nivåer i cancervävnad visade sig vara associerat med en halverad risk för död i äggstockscancer. En förklaring till de lägre nivåerna uPAR i de mest aggressiva tumörerna kan vara att receptorn inkorporeras och bryts ned inne i tumörcellerna eller borttransporteras via blodet. Höga uPA nivåer visade sämre prognos.
Resultaten i avhandlingen belyser att äggstockscystor är relativt vanligt hos fertila kvinnor men att cystorna oftast spontant försvinner inom tre månader. Resultaten tyder också på en ökad risk för äggstockscancer om kvinnan tidigare behandlats för cysta på äggstocken, även om cystan tagits bort. I äggstockscancervävnad produceras uPA, uPAR och PAI-1 främst i bindvävscellerna men aktiviteten av uPA sker kring cancercellerna. Höga uPAR-koncentrationer indikerar bättre prognos liksom låga uPA-nivåer pekar mot bättre prognos på lång sikt för patienterna med äggstockscancer. Framöver bör givetvis resultaten bekräftas av ytterligare studier avseende sambandet äggstockscystor och äggstockscancer, uPARs och uPAs prognostiska betydelse. Om PA-systemets komponenter i blodprov kan visa på tidig diagnos eller är av prognostisk betydelse för patienter med äggstockscancer återstår också att studera. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/42054
- author
- Borgfeldt, Christer LU
- supervisor
- opponent
-
- Docent Brännström, Mats, Department of Obstetrics and Gynecology, Göteborg University, Sweden
- organization
- publishing date
- 2001
- type
- Thesis
- publication status
- published
- subject
- keywords
- reproduktion, andrologi, gynekologi, sexuality, Obstetrik, Ovarian neoplasm, andrology, reproduction, epidemiology, ultrasonography, plasminogen activation, prognosis, gynaecology, Obstetrics, sexualitet
- pages
- 162 pages
- publisher
- Department of Obstetrics and Gynecology, Lund University
- defense location
- Dept. of Obstetrics and Gynecology in the auditorium, third floor, University Hospital in Lund, Sweden
- defense date
- 2001-11-23 09:00:00
- ISBN
- 91-628-5007-5
- language
- English
- LU publication?
- yes
- id
- 4e99550b-bc05-4b88-80ab-17a83db517b1 (old id 42054)
- date added to LUP
- 2016-04-04 10:07:46
- date last changed
- 2018-11-21 20:56:56
@phdthesis{4e99550b-bc05-4b88-80ab-17a83db517b1,
abstract = {{The aims were to assess the prevalence of ovarian tumors in fertile asymptomatic women and to evaluate the risk of ovarian cancer in women with a history of benign ovarian tumors and endometriosis. In order to search for biomarkers in ovarian tumors, the plasminogen activating (PA) system was studied.<br/><br>
<br/><br>
A random sample of women 25-40 years old was invited to a transvaginal ultrasonography examination. Ovarian cysts were found in 7% (22/335). At follow-up three months later 18 of the 22 cysts had spontaneously disappeared.<br/><br>
<br/><br>
In a case-control study, The Swedish Hospital Discharge Register, The National Swedish Cancer Register, and the Fertility Register, were used to analyze the risk of developing ovarian cancer in women hospitalized with the diagnoses of ovarian cyst, functional ovarian cyst, or endometriosis. Young women (15 to 29 years old) discharged from hospital for ovarian cysts and functional cysts showed a doubled risk of developing ovarian cancer. Women with ovarian cysts who had undergone ovarian cyst resection or unilateral oophorectomy had a nine times higher risk of developing ovarian cancer. Women with endometriosis had a minor increased risk of ovarian malignancy. The risk of developing ovarian cancer was inversely related to parity and the mean age at diagnosis of ovarian cancer was lower in all three study groups as compared with the control groups.<br/><br>
<br/><br>
The gene expression of urokinase plasminogen activator (uPA), its receptor (uPAR) and inhibitor (PAI-1) was increased in malignant as compared with benign tumors, and also increased in poorly as compared with well-differentiated malignant tumors. All three mRNA species were mainly found in the stroma in poorly differentiated tumors and metastases. Stromal expression may be induced by the tumor cells. The protein levels of uPA, uPAR, uPA:PAI-1 complex were higher in malignant than in benign ovarian tumors. Furthermore, the protein content of uPA, uPA:PAI-1 complex and also PAI-1 was higher in poorly than in well-differentiated tumors. In contrast, the level of uPAR was lower in poorly than in well-differentiated malignant tumors, and also lower in advanced than in early stages of the disease. This discrepancy may be the result of increased turn-over of uPAR in poorly differentiated tumors.<br/><br>
<br/><br>
High tumor tissue content of uPAR as well as low content of uPA was associated with longer postoperative survival.}},
author = {{Borgfeldt, Christer}},
isbn = {{91-628-5007-5}},
keywords = {{reproduktion; andrologi; gynekologi; sexuality; Obstetrik; Ovarian neoplasm; andrology; reproduction; epidemiology; ultrasonography; plasminogen activation; prognosis; gynaecology; Obstetrics; sexualitet}},
language = {{eng}},
publisher = {{Department of Obstetrics and Gynecology, Lund University}},
school = {{Lund University}},
title = {{Ovarian tumors. Prevalence, malignancy risk and significance of the Plasminogen activation system.}},
year = {{2001}},
}