Apoptosis and expression of Bcl-2 and Bax proteins in invasive ductal carcinoma of the pancreas

The Bcl-2 family of genes plays important roles in the regulation of apopto sis. The present study was designed to assess the clinicopathologic signifi cance of apoptosis and the expression of the apoptosis-inhibitory Bcl-2 pro tein (pBcl-2) and the apoptosis-promoting Bax protein (pBax) in human invas ive ductal carcinomas (IDCs) of the pancreas. The present study included 66 IDCs that were resected between 1982 and 1998. Apoptosis was assessed by t he in situ nick end labeling method and pBcl-2 and pBax were stained immuno histochemically. Apoptosis was quantified as the apoptotic index (AI, the p ercentage of apoptotic cells of the total tumor cells), and a high AI (>10% ) was observed in 26 of the 66 (39%) IDCs. The Al correlated significantly with the extent of nodal involvement. pBax immunoreactivity was detected in 42 of 66 IDCs (64%), and pBax expression was significantly correlated with female gender and showed a significant negative correlation with the exten t of nodal involvement. pBcl-2 was expressed in 16 IDCs (24%) but did not s how any correlation with the clinicopathologic factors. The AI did not corr elate with the expression of pBcl-2 or pBax, but there was a significant co rrelation between the expression of pBcl-2 and that of pBax; 15 of the 16 p Bcl-2(+)IDCs were also pBax(+), and only one pBcl-2(+)IDC was pBax(-). Univ ariate analysis demonstrated that the degree of apoptosis had no significan t influence on the patients' prognosis. pBax or pBcl-2 expression was signi ficantly associated with a better prognosis, and in particular, the pBax(+) pBcl-2(+) group had a significantly higher survival than the other groups. On the other hand, the survival curve of the adjuvant chemotherapy (ACT) gr oup was also higher than that of the surgery alone (SA) group, with borderl ine statistical signfiicance. The ACT group showed a significantly better s urvival rate than the SA group for the pBax(+)IDC patients, but the Al and pBcl-2 expression were not correlated with an improved survival rate in the ACT group. Multivariate analysis showed that the AI, pBcl-2 expression, an d pBax expression by themselves did not represent significant variables for death owing to IDC, but pBax expression was significantly associated with the efficacy of ACT. In conclusion, pBax expression may be essential for pB cl-2 expression. pBcl-2 and pBax expressions are not significant prognostic factors for patients with IDC, but pBax expression may be beneficial in pr edicting the effects of ACT on patients with IDC.