title: High nuclear S100A6 (Calcyclin) is significantly associated with poor survival in pancreatic cancer patients.
abstract: Recent studies have reported elevated levels of S100A6 in pancreatic ductal adenocarcinoma cells. Here, we describe a detailed analysis of S100A6 expression in benign (n = 32), malignant (n = 60), and premalignant pancreatic ductal cells [96 pancreatic intraepithelial neoplasias (PanIN) from 46 patients]. S100A6 staining was more intense in malignant cells than in benign cells (P = 0.0001). In malignant cells, staining was higher in the nucleus than in the cytoplasm (P = 0.003). Univariate analysis revealed a significant decrease in survival time for patients with high levels of nuclear (P = 0.01) but not cytoplasmic (P = 0.20) S100A6. No evidence was found for an association between nuclear S100A6 expression and other variables, including gender, age at surgery, tumor size or grade, nodal metastases, resection margin, vascular invasion, perineural invasion, p53 or Smad4 levels (both linked to survival in previous studies), or the p65 subunit of nuclear factor-kappaB (a potential regulator of S100A6). Although nodal metastases and resection margin involvement were also associated with poor survival (P = 0.06 in both cases), multivariate analysis suggests that nuclear S100A6 is a significant independent indicator of survival (P = 0.003). Whereas PanIN 1a lesions showed a general absence of S100A6 staining, there was a progressive increase in the proportion of positively stained PanINs with increasing PanIN grade. In particular, we observed an increase in the frequency and intensity of nuclear staining. Our results suggest that up-regulation of S100A6 is an early event in pancreatic cancer development and that elevated levels of nuclear S100A6 may affect clinical outcome.
authors.affiliation: Division of Surgery and Oncology, Department of Pathology, University of Liverpool, Liverpool, Merseyside, UK.
authors.forename: Dale
authors.initials: D
authors.lastname: Vimalachandran
authors.forename: William
authors.initials: W
authors.lastname: Greenhalf
authors.forename: Christopher
authors.initials: C
authors.lastname: Thompson
authors.forename: Jutta
authors.initials: J
authors.lastname: Lüttges
authors.forename: Wendy
authors.initials: W
authors.lastname: Prime
authors.forename: Fiona
authors.initials: F
authors.lastname: Campbell
authors.forename: Andrew
authors.initials: A
authors.lastname: Dodson
authors.forename: Richard
authors.initials: R
authors.lastname: Watson
authors.forename: Tatjana
authors.initials: T
authors.lastname: Crnogorac-Jurcevic
authors.forename: Nicholas
authors.initials: N
authors.lastname: Lemoine
authors.forename: John
authors.initials: J
authors.lastname: Neoptolemos
authors.forename: Eithne
authors.initials: E
authors.lastname: Costello
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins / Q000096:biosynthesis* / Q000378:metabolism; D051996:Transcription Factor RelA
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D016328:NF-kappa B; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; D051996:Transcription Factor RelA; C055351:S100A6 protein, human