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  • Bcl-2, BAX, and apoptosis in endometrial hyperplasia after high dose gestagen therapy: a comparison of responses in patients treated with intrauterine levonorgestrel and systemic medroxyprogesterone.

Bcl-2, BAX, and apoptosis in endometrial hyperplasia after high dose gestagen therapy: a comparison of responses in patients treated with intrauterine levonorgestrel and systemic medroxyprogesterone.

Gynecologic oncology (2005-05-12)
Anne Beate Vereide, Turid Kaino, Georg Sager, Anne Ørbo
ABSTRACT

The aim of the study was to investigate apoptosis as a growth regulatory mechanism of gestagen in endometrial precancers and to compare differences in the apoptotic cascade after high and low dose gestagen regimens. Pre- and post-treatment paraffin-embedded endometrial hyperplasia specimens from women treated with levonorgestrel intrauterine device (n = 26) and women treated with 10 mg medroxyprogesterone for 10 days per cycle (n = 31) were examined for changes in the expression of Bcl-2 and BAX and the extent of apoptosis after 3 months of treatment. Immunohistochemical expression in tissue specimens for Bcl-2 and BAX was evaluated by H-score. Average number of apoptotic cells per hundred cells within ten different high power field (40 x) was evaluated for each section after in situ apoptosis detection (TUNEL method). A second group of patients with endometrial hyperplasia was examined after 1 week treatment with levonorgestrel IUD (n = 6) or medroxyprogesterone (n = 5) to determine early effects on expression of Bcl-2 and BAX and the extent of apoptosis. All the patients in the IUD group (n = 31) but only about half of the patients in per oral group (16 of 26) responded to treatment. The glandular reduction in Bcl-2 expression was markedly greater for the IUD patients than for the patients who received oral gestagen. The decrease in BAX expression after IUD treatment was less than the reduction of Bcl-2. Decrease in glandular Bcl-2 after 3 months of treatment was coincident with a significant increase in the measurable amount of apoptosis. In stromal cells, the increase in expression of Bcl-2 and BAX was found after gestagen treatment, the response being much more marked for the IUD group. The non- responders to per oral gestagen had no Bcl-2 expression in stroma after 3 months of therapy whereas an increase was observed for the responders. After 1 week, glandular Bcl-2 expression was significantly reduced after treatment in the IUD group. As for the rest, no changes were detected in either of the groups. Our results indicate that proteins in the apoptotic cascade are regulated by gestagen therapy in human endometrial precancers. Expression of these proteins is shown to be dependent on administration form and/or type of gestagen. Stromal Bcl-2 expression appears to be a potential biomarker which can separate responders of gestagen treatment from non-responders after oral administration.

MATERIALS
Product Number
Brand
Product Description

Supelco
ORBO 609 Amberlite XAD®-2 (20/50) 400/200 mg, W,W,W separators, O.D. × L 8 mm × 110 mm, pkg of 50 ea
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ORBO 402 Tenax® TA specially treated (35/60), 100/50 mg, W,W,W separators, O.D. × L 8 mm × 100 mm, pkg of 50 ea
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ORBO 80 Coated Filter, with cassettes unassembled
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ORBO 554 H2SO4 on Silica Gel (20/40) 150/75 mg, W,W,W separators, O.D. × L 6 mm × 75 mm, pkg of 50 ea
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ORBO 23 2-HMP on Amberlite XAD®-2 (20/40), 120/60 mg, W,W,W separators, O.D. × L 6 mm × 85 mm, pkg of 25 ea
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ORBO 49P (OVS) Supelpak-20 specially treated Amberlite XAD®-2 (20/40), 270/140 mg, RC,GFF,F,F (specially cleaned) separators, O.D. × L 13-8 mm × 75 mm , OSHA Versatile Sampler (OVS) Tube, pkg of 10 ea
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ORBO 502 Activated Silica Gel (20/45) 100/50 mg, W,W,F separators, O.D. × L 6 mm × 75 mm, pkg of 50 ea
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ORBO 65P (OVS) Amberlite XAD®-4 specially cleaned, 160/80 mg, RC,GFF,F,F (specially cleaned) separators, O.D. × L 13-8 mm × 75 mm , OSHA Versatile Sampler (OVS), pkg of 10 ea
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ORBO 52 Small Activated Silica Gel (20/40) 150/75 mg, pk 50, W,W,F separators, O.D. × L 6 mm × 75 mm, pkg of 50 ea
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ORBO 43 Supelpak-20 specially treated Amberlite XAD®-2 (20/40), 100/50 mg, W,W,W (specially treated) separators, O.D. × L 8 mm × 100 mm, pkg of 50 ea
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ORBO 92 Carboxen® 564 (20/45), 160/80 mg, W,F,F separators, O.D. × L 6 mm × 75 mm, pkg of 25 ea, for analyte group Vinyl acetate