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Abstract Background Pancreatic cancer, including cancer of the ampulla of Vater and bile duct, is very aggressive and has a poor five year survival rate; improved methods of patient stratification are required. Methods We assessed the expression of calpain-1, calpain-2 and calpastatin in two patient cohorts using immunohistochemistry on tissue microarrays. The first cohort was composed of 68 pancreatic adenocarcinomas and the second cohort was composed of 120 cancers of the bile duct and ampulla. Results In bile duct and ampullary carcinomas an association was observed between cytoplasmic calpastatin expression and patient age (P = 0.036), and between nuclear calpastatin expression and increased tumour stage (P = 0.026) and the presence of vascular invasion (P = 0.043). In pancreatic cancer, high calpain-2 expression was significantly associated with improved overall survival (P = 0.036), which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.342; 95% confidence interva l = 0.157-0.741; P = 0.007). In cancers of the bile duct and ampulla, low cytoplasmic expression of calpastatin was significantly associated with poor overall survival (P = 0.012), which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.595; 95% confidence interval = 0.365-0.968; P = 0.037). Conclusion The results suggest that calpain-2 and calpastatin expression is important in pancreatic cancers, influencing disease progression. The findings of this study warrant a larger follow-up study.

Morphometry [nuclear Ki-67 labelling, mitotic activity index (MI), and volume-corrected mitotic index (M/V)] for periampullary cancers using tissue microarrays has not been performed previously. The purpose of the study was to assess these indices on tissue microarray (TMA) sections constructed from patients with periampullary cancers and study their association with clinicopathological variables. Immunohistochemical staining for Ki-67 was performed on formalin-fixed pancreatic TMA sections. Expression of Ki-67 was assessed as the percentage of cancer cell nuclei expressing MIB1, MI as the mean percentage of Ki-67 from 10 random high-power fields, and M/V was calculated after standardizing MI for connective tissue volume and microscope parameters in the tumor using established protocols. Patients ≥70 years with periampullary cancers had higher Ki-67 expression (>15) compared with patients <70 years of age (χ2 = 3.9, P = 0.047). Ki-67 expression was higher in tumors ≥2 cm (χ2 = 4.9, P = 0.028) compared with smaller tumors. Higher MI (>15) was clearly associated with worsening histological grade (χ2 = 9.2, P = 0.010). The median survival for tumors of the pancreaticobiliary subtype (pancreatic ductal adenocarcinoma and cholangiocarcinoma) was 43 months in the group with an M/V score of <20, compared with 18 months for the group with a score ≥20 ( P = 0.001). There was no statistically significant difference in survival, based on M/V score, for tumors of the intestinal subtype (ampullary and duodenal adenocarcinoma). In periampullary cancers, Ki-67 and MI are proliferative indices predictive of tumor behavior. M/V was predictive of survival in tumors of the pancreaticobiliary subtype. [ABSTRACT FROM AUTHOR]

Gossage L, Zaitoun A, Fareed K R, Turley H, Aloysius M, Lobo D N, Harris A L & Madhusudan S (2010) Histopathology 56, 908–920 Expression of key hypoxia sensing prolyl-hydroxylases PHD1, -2 and -3 in pancreaticobiliary cancer Aims: Tumour hypoxia is associated with an aggressive phenotype and resistance to chemotherapy and radiotherapy. The aim was to investigate whether key hypoxia sensing prolyl hydroxylases PHD1, PHD2 and PHD3 are dysregulated in pancreaticobiliary cancers, and to evaluate their potential clinical significance. Methods and results: Formalin-fixed human pancreatic tissue from 120 consecutive patients undergoing pancreatic resections between June 2001 and June 2006 was constructed into tissue microarrays. Expression of PHD1, PHD2 and PHD3 was analysed using immunohistochemistry and correlated with clinicopathological variables and disease-specific overall survival. PHD1, PHD2 and PHD3 were significantly overexpressed in pancreaticobiliary tumours compared with normal pancreatic ductal tissues ( P = 0.03, P < 0.0001 and P < 0.0001, respectively). PHD3 expression in tumour tissue was associated with a trend towards worse overall disease-specific survival in ampullary adenocarcinomas ( P = 0.035) and pancreatic adenocarcinomas ( P = 0.084). Absence of PHD1 expression was significantly associated with perineural invasion in pancreatic adenocarcinomas ( P = 0.02) and a trend towards significance was also seen for absence of PHD2 expression in pancreatic adenocarcinomas ( P = 0.04). Conclusions: Our results provide the first clinical evidence that PHD1, PHD2 and PHD3 may be involved in pancreaticobiliary tumorigenesis. [ABSTRACT FROM AUTHOR]