High expression of RelA/p65 is associated with activation of nuclear factor-kappaB-dependent signaling in pancreatic cancer and marks a patient population with poor prognosis.
Activation of nuclear factor-kappaB (NF-kappaB) signaling was observed in pancreatic adenocarcinoma cell lines and tumours. However, information on the expression of RelA/p65, the major transcription activating NF-kappaB subunit, in these carcinomas and possible correlations thereof with NF-kappaB activation and patient survival is not available. To provide this missing translational link, we analysed expression of RelA/p65 in 82 pancreatic adenocarcinomas by immunohistochemistry. Moreover, we measured activation of the NF-kappaB pathway in 11 tumours by quantitative PCR for NF-kappaB target genes. We observed strong cytoplasmic or nuclear expression of RelA/p65 in 42 and 37 carcinomas, respectively. High cytoplasmic and nuclear expression of RelA/p65 had negative prognostic impact with 2-year survival rates for patients without cytoplasmic or nuclear RelA/p65 positivity of 41 and 40% and rates for patients with strong cytoplasmic or nuclear RelA/p65 expression of 22 and 20%, respectively. High RelA/p65 expression was correlated to increased expression of NF-kappaB target genes. The observation that high expression of RelA/p65 is correlated to an activation of the NF-kappaB pathway and indicates poor patient survival identifies a patient subgroup that might particularly benefit from NF-kappaB-inhibiting agents in the treatment of pancreatic cancer. Based on our findings, this subgroup could be identified by applying simple immunohistochemical techniques.
Weichert
W
W
Institute of Pathology, Charité University Hospital, Berlin, Germany. wilko.weichert@charite.de
Boehm
M
M
Gekeler
V
V
Bahra
M
M
Langrehr
J
J
Neuhaus
P
P
Denkert
C
C
Imre
G
G
Weller
C
C
Hofmann
H-P
HP
Niesporek
S
S
Jacob
J
J
Dietel
M
M
Scheidereit
C
C
Kristiansen
G
G
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D011379:Prognosis; D015398:Signal Transduction; D016019:Survival Analysis; D051996:Transcription Factor RelA / Q000235:genetics* / Q000378:metabolism
D014408:Biomarkers, Tumor; D016328:NF-kappa B; D051996:Transcription Factor RelA