The potential role of bcl-2, bax, and Ki67 expression in thymus of patients with myasthenia gravis, and their correlation with clinicopathologic parameters.
OBJECTIVE
The aim of this study was to evaluate bcl-2, bax (apoptotic-oncoproteins), and Ki67 (cell proliferation-marker) expression in thymus of patients with myasthenia gravis (MG) and to determine the potential correlation with clinicopathologic parameters.


METHODS
The study was done on 38 patients (16 males, 22 females; mean age 38+/-10 years) with MG who underwent modified maximal thymectomy (MMT). Clinical staging (Osserman classification) included stage I in three, IIA in 19, IIB in 13 and III in three. Microscopic examination of thymus showed thymic hyperplasia in 19, atrophy in eight, thymoma in nine and thymic carcinoma in two. On paraffin sections, the streptavidin-biotin technique, using antibodies to bcl-2, bax, and Ki67, was employed, and in situ hybridization with digoxigenin-labeled probes to bcl-2 and bax was performed. In addition, the apoptotic body index (ABI) was assessed via the TUNEL method. Staining results were correlated with clinicopathologic parameters.


RESULTS
Bcl-2 expression was higher in hyperplasia and thymoma cases, compared to thymic carcinomas (P<0.001). Higher expression in carcinomas, compared to hyperplasia and thymomas, was observed for bax (P<0.001), Ki67 (P<0.001) and ABI (P<0.001). Statistical analysis demonstrated: (A) positive correlation of bax+ cells with MG stage (P<0.001), ABI and %Ki67+ cells with MG stage (P<0.001, respectively), %Ki67+ and %bax+ cells with ABI (P<0.05); and (B) reverse correlation between %bcl-2+ cells and MG stage (P<0.05).


CONCLUSIONS
In patients with MG who underwent MMT, bcl-2, bax, and Ki67 expression correlates positively or reversibly with the microscopic findings of thymus. Increased apoptosis and proliferation accompany advanced disease stage and possible worse prognosis.
Salakou
S
S
Department of Neurology, University of Patras, School of Medicine, Patras, Greece.
Tsamandas
A C
AC
Bonikos
D S
DS
Papapetropoulos
T
T
Dougenis
D
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology; D002277:Carcinoma / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D006965:Hyperplasia; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000473:pathology* / Q000601:surgery; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D013934:Thymectomy; D013945:Thymoma / Q000473:pathology* / Q000601:surgery; D013950:Thymus Gland / Q000473:pathology*; D013953:Thymus Neoplasms / Q000473:pathology* / Q000601:surgery; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D019394:Ki-67 Antigen; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein