HMGA1 correlates with advanced tumor grade and decreased survival in pancreatic ductal adenocarcinoma.
Although pancreatic ductal adenocarcinoma is a common and almost uniformly fatal cancer, little is known about the molecular events that lead to tumor progression. The high-mobility group A1 (HMGA1) protein is an architectural transcription factor that has been implicated in the pathogenesis and progression of diverse human cancers, including pancreatic ductal adenocarcinoma. In this study, we investigated HMGA1 expression in pancreatic ductal adenocarcinoma cell lines and surgically resected tumors to determine whether it could be a marker for more advanced disease. By real-time quantitative RT-PCR, we measured HMGA1a mRNA in cultured pancreatic ductal adenocarcinoma cell lines and found increased levels in all cancer cells compared with normal pancreatic tissue. To investigate HMGA1 in primary human tumors, we performed immunohistochemical analysis of 125 cases of pancreatic adenocarcinoma and 99 precursor lesions (PanIN 1-3). We found nuclear staining for HMGA1 in 98% of cases of pancreatic adenocarcinoma, but only 43% of cases of PanIN precursor lesions. Moreover, HMGA1 immunoreactivity correlates positively with decreased survival and advanced tumor and PanIN grade. These results suggest that HMGA1 promotes tumor progression in pancreatic ductal adenocarcinoma and could be a useful biomarker and rational therapeutic target in advanced disease.
Hristov
Alexandra C
AC
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Cope
Leslie
L
Di Cello
Francescopaolo
F
Reyes
Marcelo Delos
MD
Singh
Mansher
M
Hillion
Joelle A
JA
Belton
Amy
A
Joseph
Biju
B
Schuldenfrei
Andrew
A
Iacobuzio-Donahue
Christine A
CA
Maitra
Anirban
A
Resar
Linda M S
LM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D025741:HMGA1a Protein / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D025741:HMGA1a Protein