Evaluation of osteopontin as biomarker for pancreatic adenocarcinoma.
OBJECTIVE
Pancreatic adenocarcinoma is a deadly disease with an overall 5-year patient survival of less than 5%. This dismal prognosis of pancreatic cancer is largely due to the advanced stage of the disease at presentation. If pancreatic cancer could be diagnosed more readily and accurately using serum markers, patient survival could theoretically be improved by enabling more patients to avail of surgical resection. One candidate tumor marker recently identified by global gene expression analysis of pancreatic cancer is the secreted glycophosphoprotein osteopontin (OPN). In this study, we evaluate OPN as a serum marker of pancreatic adenocarcinoma.


METHODS
In situ hybridization for OPN was performed on a pancreatic adenocarcinoma tissue microarray. Serum OPN levels were determined in preoperative sera from 50 patients with pancreatic cancer and 22 healthy control individuals by competitive ELISA.


RESULTS
In situ hybridization for OPN performed on a tissue microarray revealed strong OPN mRNA signal in tumor-infiltrating macrophages in 8 of 14 pancreatic adenocarcinomas. In contrast, OPN expression was not seen in the pancreatic cancer cells themselves, nor was it seen in normal pancreatic tissue or in the macrophages distant from the infiltrating cancer. Serum OPN levels, as measured by ELISA, were elevated in the sera of 50 patients with resectable pancreatic adenocarcinoma compared to 22 healthy control individuals (mean +/- SD for OPN was 482 +/- 170 ng/ml and 204 +/- 65 ng/ml, respectively; P < 0.001). Using a cutoff level of 2 SD above the mean for healthy individuals, elevated OPN had sensitivity of 80% and specificity of 97% for pancreatic cancer. In contrast, only 62% of these patients with resectable pancreatic cancer had elevated CA19-9.


CONCLUSIONS
Serum OPN may have utility as a diagnostic marker in patients with pancreatic cancer.
Department of Pathology and Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Jens
J
Koopmann
Neal S
NS
Fedarko
Alka
A
Jain
Anirban
A
Maitra
Christine
C
Iacobuzio-Donahue
Ayman
A
Rahman
Ralph H
RH
Hruban
Charles J
CJ
Yeo
Michael
M
Goggins
D000230:Adenocarcinoma / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D017403:In Situ Hybridization; D008264:Macrophages; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D053495:Osteopontin; D010190:Pancreatic Neoplasms / Q000473:pathology*; D012680:Sensitivity and Specificity; D012795:Sialoglycoproteins / Q000032:analysis* / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin