Expression analysis of apoptosis-related markers TP53, BCL-2, BAX and c-MYC in female genital tract sarcomas.
BACKGROUND
Most female genital tract sarcomas are highly malignant and fatal. Their aggressive growth pattern and poor response to chemotherapy are the major causes of death. Deregulation of the apoptosis pathway is related to tumorigenesis and chemodrug resistance. The purpose of this study was to investigate the expression status and relationship of the apoptosis-related markers TP53, BCL-2, BAX and c-MYC in this group of tumors. In addition, correlations of these markers with clinicopathologic findings and their prognostic significance were also examined.


METHODS
Paraffin blocks of female genital tract sarcoma tissue from 54 patients were obtained after pathology review. Protein expression of TP53, BCL-2, BAX and c-MYC was examined using immunohistochemical staining with standard procedures. A semiquantitative method was used to assess the staining result where scoring 1-3 was negative and 4-9 was positive for expression. The mutual relationships between TP53, BCL-2, BAX and c-MYC were examined. Associations between expression of the apoptotic markers and tumor stage as well as outcome were also analyzed.


RESULTS
We found that all 4 of the apoptosis-related markers were frequently expressed in female genital tract sarcomas. Of the 54 cases, 24 (44%) were positive for TP53, 23 (43%) for BCL-2, 25 (46%) for BAX, and 30 (56%) for c-MYC. A significant positive association was observed between BAX and c-MYC (p < 0.001). There was no significant difference for the expression status of the 4 markers in early and late stage tumors. In prognostic analysis, overexpression of TP53, late stage, and age were significant prognostic factors in both univariate and multivariate analyses.


CONCLUSIONS
Since changes in TP53, BCL-2, BAX and c-MYC frequently occur in female genital tract sarcomas, deregulation of apoptosis appears to be involved in the pathogenesis of this group of tumors. This mechanism may occur early in tumorigenesis and include the c-MYC/BAX apoptotic pathway or BCL-2. However, TP53 mutation may play a crucial role in this process, and clinically, it could be used as a prognostic indicator.
Liu
Fu-Shing
FS
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan, ROC. fsliu1217@yahoo.com.tw
Jan
Yee-Jee
YJ
Lai
Chiung-Ru
CR
Twu
Nae-Fang
NF
Lu
Chien-Hsing
CH
Hung
Man-Jung
MJ
Hsieh
Yeun-Ting
YT
Chiou
Li-Ching
LC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005260:Female; D005833:Genital Neoplasms, Female / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis*; D012509:Sarcoma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D051028:bcl-2-Associated X Protein / Q000032:analysis*
C489427:MYC protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein