Cytokeratin 20 expression identifies a subtype of pancreatic adenocarcinoma with decreased overall survival.
BACKGROUND
Cytokeratins are markers of epithelial cell differentiation useful in determining histogenesis for malignancies with an unknown primary. Application of this principle to a single malignancy may identify cancer subtypes with altered developmental programs. Herein, we investigate the relevance of two widely used cytokeratins (CKs), 7 and 20, to subtype pancreas cancer and identify associations with clinical features.


METHODS
A tissue microarray was constructed using tumor specimens from 103 patients who underwent resection for pancreatic adenocarcinoma with curative intent. A subset of resection specimens was evaluated for pancreatic intraepithelial neoplasia (PanIN) lesions. Tissues were immunostained by using specific anticytokeratin 7 and 20 monoclonal antibodies.


RESULTS
CK 7 and 20 expression was present in 96% and 63% cases of pancreatic adenocarcinoma, respectively. Ubiquitous CK 7 expression precluded further analysis. Tumoral CK 20 expression was not associated with any histopathologic parameter but correlated with worse prognosis when considered as either a dichotomous (P=0.0098) or continuous (P=0.007) variable. In a multivariate model, tumoral CK 20 expression remained a significant independent prognosticator. CK 20 expression was absent in all PanIN lesions from eight resection specimens in which the tumor component was negative for CK 20. In contrast, presence of tumoral CK 20 was highly concordant with its expression in corresponding PanINs.


CONCLUSIONS
CK 20 expression defines a subtype of pancreas cancer with important biologic properties. When present, CK 20 expression is an early event in pancreatic carcinogenesis identifiable in precursor lesions. Further studies to identify the underlying genetic changes associated with this altered developmental pathway are warranted.
Matros
Evan
E
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Bailey
Gerald
G
Clancy
Thomas
T
Zinner
Michael
M
Ashley
Stanley
S
Whang
Edward
E
Redston
Mark
M
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053554:Keratin-20; D053552:Keratin-7; D007633:Keratins / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis
C507499:KRT20 protein, human; C507497:KRT7 protein, human; D053554:Keratin-20; D053552:Keratin-7; D007633:Keratins