Time to progression is dependent on the expression of the tumour suppressor PTEN in ovarian cancer patients.
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.


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 protein kinase 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.
Schöndorf
T
T
Department of Gynecology and Obstetrics, University of Cologne, Cologne, Germany.
Göhring
U-J
UJ
Roth
G
G
Middel
I
I
Becker
M
M
Moser
N
N
Valter
M M
MM
Hoopmann
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000209:etiology / Q000378:metabolism*; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000302:isolation & purification; D051057:Proto-Oncogene Proteins c-akt; D025521:Tumor Suppressor Proteins / Q000302:isolation & purification / Q000378:metabolism*
D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human