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Time to progression is dependent on the expression of the tumour suppressor PTEN in ovarian cancer patients
Author(s) -
Schöndorf T.,
Göhring U.J.,
Roth G.,
Middel I.,
Becker M.,
Moser N.,
Valter M. M.,
Hoopmann M.
Publication year - 2003
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2003.01116.x
Subject(s) - pten , cancer research , ovarian cancer , cancer , protein kinase b , tumor progression , oncology , medicine , biology , phosphorylation , pi3k/akt/mtor pathway , apoptosis , biochemistry
Background Quantitative analyses of PTEN expression of ovarian cancer tissues were performed in this study. PTEN expression was investigated in terms of each patient's progression‐free interval to indicate the role of PTEN in the generation of platinum refractory tumours. Materials and methods The study group comprised 20 ovarian cancer patients from whom fresh frozen tissues of both the primary tumour and specimens of progressive disease were available. The PTEN protein and phosphorylation of the downstream effector proteinkinase B (PKB) were quantified by Western blot analyses and subsequent densitometry. Data were analyzed for individual PTEN variation with respect to the clinical course as defined by the progression‐free interval. Results Applying the usual clinical criteria for platinum‐sensitivity after progression, seven patients were considered platinum‐sensitive whereas 13 patients had suffered a progression within 12 months after the chemotherapy. In 5/7 (71%) cases with prolonged time to progression, an increase in PTEN was observed. Decline of PTEN expression occurred in 9/13 (69%) patients with poor outcome. PTEN expression corresponds inversely to PKB phosphorylation in 14/20 (70%) tissues investigated. Conclusions The data suggest that decreased PTEN expression accompanies the progression of ovarian cancer. Declining PTEN expression results in a shortened relapse‐free interval, whereas an increase of PTEN prolongs the time to progression. However, as far as recurrence occurs, PTEN is not the only mechanism to suppress tumour progression in ovarian cancer.