Expression of cyclin D1 in bone marrow of multiple myeloma patients before and after bortezomib treatment

Abstract

Cilj: Imunohistokemijski procijeniti ekspresiju ciklina D1 na mijelomskim stanicama u koštanoj srži pacijenata s multiplim mijelomom (MM), liječenih bortezomibom te dobivene podatke usporediti s kliničko-patološkim parametrima i odgovorom na terapiju. Ispitanici i metode: Ekspresija ciklina D1 analizirana je ubioptičkim uzorcima koštane srži 24 pacijenta s MM-om prije i nakon provedene terapije bortezomibom. Za određivanje ekspresije ciklina D1 na mijelomskim stanicama korištena je dvostruka imunohistokemijska metoda koja omogućava istovremeno bojanje uzorka s dva protutijela (u ovom slučaju s CD138 za identifikaciju plazma stanica i ciklinom D1). Pozitivnom reakcijom smatralo se nuklearno obojenje naciklin D1, bilo kojeg intenziteta, u ≥ 10 % plazma stanica. Rezultati su potom korelirani s kliničko-patološkim podacima pacijenata ispitivane skupine. Rezultati: Nuklearna ekspresija ciklina D1 u plazma stanicama oboljelim od MM-a prije terapije nađena u je 9/24 pacijenta, a ukupno negativnih pacijenata bez ikakvog nuklearnog bojanja 13/24 ili s bojanjem na ciklin D1 u < 10 % stanica 2/24 bilo je 15/24. Nakon terapije bortezomibom 5/24 pacijenta bilo je pozitivno na ciklin D1, dok je ukupno 19/24 pacijenata bilo negativno, tj. bez ikakvog nuklearnog bojanja 17/24 ili je imalo < 10 % tumorskih stanica 2/24 pozitivno na ciklin D1. U ovoj studiji nije nađena statistički značajna razlika u ekspresiji ciklina D1 prije i nakon provedene terapije bortezomibom (p = 0,084) niti s nekim od kliničko-patoloških parametara. Zaključak: Rezultati i razina ekspresije ciklina D1 uvelike variraju unutar različitih ispitivanih skupina, a također ovise i o terapiji koju su pacijenti dobivali, stoga je za utvrđivanje značaja ciklina D1 na prognozu i korelaciju s kliničko- -patološkim karakteristikama potrebna veća i homogenija skupina pacijenata.Objective: To evaluate, immunohistochemically expression of cyclin D1 in myeloma cells in the bone marrow of multiple myeloma (MM) patients treated with bortezomib and compare obtained data with clinico-pathological parameters and response to therapy. Patients and methods: Twenty four patients with MM treated with bortezomib were included in this study. To determine the expression of cyclin D1 in the bone marrow prior to and after bortezomib treatment, we used double immunohistochemical method, which allows simultaneous staining of the sample with two antibodies (in this case with CD138 (plasma cell marker) and cyclin D1). A positive reaction was considered when ≥ 10% plasma cells showed cyclin D1 nuclear staining, at any intensity. The results were correlated with patient’s clinicopathological data. Results: The nuclear expression of cyclin D1 in the plasma cells of patients with MM before therapy was found in 9/24 cases and there was 15/24 negative patients, including patients without any nuclear staining 13/24 or with nuclear staining for cyclin D1 but in < 10% of plasma cells 2/24. After bortezomib tretament, 5/24 patients were positive for cyclin D1 while 19/24 patients were negative, including patients without any nuclear staining 17/24 or they had < 10% of cyclin D1 positive tumor cells 2/24. In this study there was no statistically significant difference in the expression of cyclin D1 before and after bortezomib treatment (p = 0.084) as well as any correlation with some of the clinical or pathological parameters. Conclusion: The results and the level of expression of cyclin D1 vary within different study groups and depend as well on the prior treatment patients received. Therefore to determine the prognostics significance of cyclin D1 expression and its correlation with clinico-pathological features a larger and more homogeneous group of patients is required

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