Bcl-XL protein levels determine apoptotic index in pancreatic carcinoma.
OBJECTIVE
The present study was designed to analyze the expression of the major antiapoptotic molecules Bcl-2, Bcl-XL and the proapoptotic Bax in pancreatic ductal carcinoma and their correlation to the extent of apoptosis.


METHODS
Tissue samples were obtained from patients (age, 27-78 years) having surgery for pancreatic cancer. Normal pancreatic tissue away from the main tumor mass was also analyzed. The levels of Bcl-2, Bcl-XL, and Bax mRNA expression were analyzed by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). The presence of corresponding proteins was determined by immunohistochemistry (IHC). The apoptotic index was determined by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay.


RESULTS
A total of 25 cases were analyzed. The apoptotic index (percentage) ranged from 0.0% to 1.8%, with a median of 0.26. Semiquantitative RT-PCR revealed variable mRNA expression, with the Bcl-2/Bax ratio ranging from 0.2 to 1.5 and the Bcl-XL/Bax ratio ranging from 0.3 to 1.8. There was no correlation of mRNA levels with the apoptotic index. Immunohistochemical analysis showed positive Bcl-2, Bax, Bcl-XL expression in 20%, 72%, and 92% of cancer samples; however, their levels were variable. Spearman rank correlation coefficient test revealed a significant inverse association for the Bcl-XL IHC score and apoptotic index (P < 0.05). In contrast, Bcl-2, Bax protein levels did not show any association with the apoptotic index. However, as compared with the normal pancreas, Bcl-2, Bcl-XL, Bax were overexpressed in most of the pancreatic cancer samples (Mann-Whitney U test, P < 0.01).


CONCLUSIONS
In pancreatic cancer, there is an upregulation of all the apoptotic regulatory molecules and the apoptotic index is chiefly determined by Bcl-XL protein levels.
Sharma
Jyotika
J
Department of General Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Srinivasan
Radhika
R
Majumdar
Siddhartha
S
Mir
Snober
S
Radotra
Bishan Dass
BD
Wig
Jai Dev
JD
D000328:Adult; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism*
C494811:BCL2L1 protein, human; D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein