Immunohistochemical validation of a novel epithelial and a novel stromal marker of pancreatic ductal adenocarcinoma identified by global expression microarrays: sea urchin fascin homolog and heat shock protein 47.
We extended the results of a previous microarray analysis by immunohistochemical validation of differential protein expression in a series of 57 surgically resected infiltrating ductal pancreatic adenocarcinomas. Two representative genes were examined: sea urchin fascin homolog (overexpressed in both cell lines and primary tumors) and heat shock protein 47 (HSP47; overexpressed in primary tumors only). Protein expression also was evaluated in the precursor lesions of pancreatic cancer pancreatic intraepithelial neoplasia (PanIN), and normal ductal epithelium. Fascin expression was seen in the neoplastic cells of 54 (95%) of 57 ductal adenocarcinomas but not in 49 (94%) of 52 adjacent nonneoplastic epithelium. In the multistep pathogenesis of ductal adenocarcinomas, fascin expression seemed to be a late event, usually present in PanINs 2 and 3. HSP47 expression was almost universal and most intense in the ductal adenocarcinoma-associated stromal desmoplasia (57/57), although 37 cases (65%) also expressed HSP47 in the neoplastic epithelium. HSP47 expression was absent in the majority of nonneoplastic pancreata (46 [88%]). Fascin and HSP47 are novel tumor markers with potential diagnostic and therapeutic implications for pancreatic carcinoma. These results establish the usefulness of global expression platforms to identify novel tumor markers.
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
Anirban
A
Maitra
Christine
C
Iacobuzio-Donahue
Ayman
A
Rahman
Taylor A
TA
Sohn
Peter
P
Argani
Renee
R
Meyer
Charles J
CJ
Yeo
John L
JL
Cameron
Michael
M
Goggins
Scott E
SE
Kern
Raheela
R
Ashfaq
Ralph H
RH
Hruban
Robb E
RE
Wilentz
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D002278:Carcinoma in Situ / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002452:Cell Count; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012334:RNA, Neoplasm / Q000032:analysis; D012617:Sea Urchins
D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008840:Microfilament Proteins; D012334:RNA, Neoplasm; C494660:SERPINH1 protein, human; C020324:fascin