Apoptotic index or a combination of Bax/Bcl-2 expression correlate with survival after resection of pancreatic adenocarcinoma

Abstract

In the present study, the prognostic impact of factors involved in the apoptosis pathway were tested on 67 consecutive patients treated with surgical resection. Included in the study were all patients resected for pancreatic adenocarcinoma from 1988 to 2003. Expression analysis for p53, Bax, and Bcl-2 were performed by immunohistochemical staining. Apoptotic cells were identified by the TUNEL method. These data were correlated with survival. Sixty-seven tumor specimens were included in the study. A strong positive correlation was recorded between p53 overexpression and Bax expression levels (P < 0.001). By univariate analysis, overall survival seemed to be improved with Bcl-2 and Bax expression (respectively, P = 0.0379 and 0.0311). The median survival time in patients with low apoptotic index was better versus those with a high index (P = 0.0127). Lymph node involvement was the only clinico-pathologic parameter that significantly correlated with overall survival (P = 0.0202). By a multivariate Cox regression analysis, the only immunohistochemical parameter that influenced overall survival was the apoptotic index (P = 0.040). Tumor's overexpression of both Bax and Bcl-2 resulted the strongest independent prognostic factor (P = 0.013). This is the first study to report a statistically significant association of apoptosis to overall survival for pancreatic cancer patients treated with surgical resection. The contemporary overexpression of Bax and Bcl-2 represents the strongest prognostic factor.

Tissue Biomarkers for Prognosis in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-analysis

“…Of 84 studies, 11 assessed the prognostic utility of multiple markers (28, 49, 57, 80-82, 86, 89, 90, 94, 102, 123). Notably, apoptotic marker combinations were more powerful than single protein evaluation (49,80,90). A combination of DNA damage repair enzymes also outperformed single marker estimations (82).…”

Molecular mechanism of pancreatic cancer—understanding proliferation, invasion, and metastasis

“…The two anti-apoptotic BCL2-family members BCL XL and MCL-1 are upregulated in PDAC cells [80][81][82][83]. Conversely, the proapoptotic BAX protein is reduced in approximately 50% of PDAC [84,85].…”

Diagnostic value of selected markers and apoptotic pathways for pancreatic cancer

“…Expression analysis of p53, Bax, and Bcl-2 using immunohistochemical staining demonstrated a statistically significant association of apoptosis with the overall survival in pancreatic cancer patients treated with surgical resection. The overexpression of Bax and Bcl-2 represents the strongest prognostic factor [96]. These data underscore the need to pay more attention to the intracellular signaling pathways that delay apoptosis of cancer cells.…”