Cyclin D1 and bax influence the prognosis after pancreatoduodenectomy for periampullary adenocarcinoma.
OBJECTIVE
The outcome of patients undergoing pancreatoduodenectomy for periampullary adenocarcinoma is influenced by various clinicopathological factors, chemo/radiotherapy and expression of various oncogenes, tumor suppressor genes, growth factors and factors controlling apoptosis. The aim of this study was to define clinicopathological predictors of survival in periampullary adenocarcinoma, and to determine the prognostic significance of cyclin D1, p27kip1 and bax expression in these tumors.


METHODS
Prospectively, we collected clinicopathological data for patients operated on between January 1995 and December 1998. Cyclin D1, p27kip1 and bax expression was assessed immunohistochemically. The potential influence of clinicopathological factors and cyclin D1, p27kip1 and bax expression on survival was investigated. Univariate analyses were performed using the Kaplan-Meier method and log-rank test. For multivariate analysis Cox proportional hazards regression was used.


RESULTS
Fifty-five patients were included in the study. The actuarial 5-year survival was 30%: 11% for pancreatic adenocarcinoma and 46% for distal bile duct/papillary adenocarcinoma Univariate analysis identified diabetes mellitus, blood transfusion, diameter of the tumor, histological type of the tumor, lymphatic invasion, neural invasion, lymph node metastasis, overexpression of cyclin D1 and lower expression of bax and p27kip1 as factors that significantly decrease survival rates. In multivariate analysis, the histological type of the tumor (p=0.001), lymph node involvement (p=0.03) and overexpression of cyclin D1 (p=0.02) independently influenced survival, whereas decreased expression of bax nearly reached statistical significance (p=0.054).


CONCLUSIONS
Our findings confirm the association between cyclin D1 and bax expression and aggressive biological behavior of periampullary adenocarcinomas. Moreover, these parameters were identified as independent prognostic indicators in these tumors.
Tomazic
Ales
A
Department of Abdominal Surgery, University Medical Centre Ljubljana, Slovenia. ales.tomazic@kclj.si
Pegan
Vladislav
V
Ferlan-Marolt
Ksaverija
K
Pleskovic
Alojz
A
Luzar
Bostjan
B
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D000328:Adult; D000368:Aged; D014670:Ampulla of Vater / Q000473:pathology / Q000601:surgery*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001707:Biopsy, Needle; D003138:Common Bile Duct Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D019938:Cyclin D1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016577:Pancreaticoduodenectomy / Q000379:methods* / Q000401:mortality; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012680:Sensitivity and Specificity; D015996:Survival Rate; D016896:Treatment Outcome; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019938:Cyclin D1