TY - JOUR
T1 - Loss of Stk11/Lkb1 expression in pancreatic and biliary neoplasms
AU - Sahin, Fikret
AU - Maitra, Anirban
AU - Argani, Pedram
AU - Sato, Norihiro
AU - Maehara, Naoki
AU - Montgomery, Elizabeth
AU - Goggins, Michael
AU - Hruban, Ralph H.
AU - Su, Gloria H.
N1 - Funding Information:
Copyright © 2003 by The United States and Canadian Academy of Pathology, Inc. VOL. 16, NO. 7, P. 686, 2003 Printed in the U.S.A. Date of acceptance: February 27, 2003. Supported by The Michael Rolfe Foundation, The American Cancer Society (IRG 58–005–40), The Lustgarten Foundation Grant, the NIH (R03 CA93292), and the NIH (GI-SPORE CA62924). Address reprint requests to: Gloria H. Su, Ph.D., Department of Pathology, The Johns Hopkins University School of Medicine, Ross Building 632, 720 Rutland Ave., Baltimore, MD 21205-2196; fax: 410-614-0671; e-mail: ghsu@jhmi.edu.
PY - 2003/7/1
Y1 - 2003/7/1
N2 - We have documented previously somatic mutations of STK11/LKB11, the gene responsible for Peutz-Jeghers syndrome (PJS), in a small proportion of sporadic pancreatic adenocarcinomas, intraductal papillary mucinous neoplasms (IPMNs), and biliary adenocarcinomas. In this report, we characterize the expression of Stk11, the protein product of the STK11 gene, in a larger series of pancreatic and biliary neoplasms. First, the specificity of the Stk11 antibody was established in 23 neoplasms (22 IPMNs and 1 biliary adenocarcinoma) with known STK11 gene status. Complete absence of labeling was seen in the neoplastic cells of 3 of the 3 (100%) cases with previously documented biallelic inactivation of the STK11 gene, whereas 16 of the 20 (80%) IPMNs, presumably with at least one wild-type STK11 gene, retained Stk11 expression in the neoplastic cells. The marked decrease or absence of Stk11 expression in four neoplasms with wild-type STK11 suggests that additional mechanisms may account for the lack of Stk11 expression. Subsequently, to further evaluate Stk11 expression in pancreatic and biliary neoplasms, tissue microarrays (TMAs) were constructed from a series of nearly 100 ductal adenocarcinomas and biliary neoplasms. Stk11 expression was lost in 4 of the 56 (7%) pancreatic adenocarcinomas and 1 of the 38 (2.6%) biliary cancers by immunohistochemistry; the absence of labeling was confirmed by repeated immunohistochemical labeling of complete tissue sections for the same cases. Thus, Stk11 expression is abrogated in a small proportion of pancreatic and biliary neoplasms. The inactivation of Stk11 in 27% (6/22) of IPMNs versus 7% (4/56) of pancreatic adenocarcinomas suggests genetic disparities in the pathogenesis of these closely related neoplasms. Immunohistochemical analysis for Stk11 expression may be a valid surrogate for genetic analysis of STK11 gene mutations in cancers.
AB - We have documented previously somatic mutations of STK11/LKB11, the gene responsible for Peutz-Jeghers syndrome (PJS), in a small proportion of sporadic pancreatic adenocarcinomas, intraductal papillary mucinous neoplasms (IPMNs), and biliary adenocarcinomas. In this report, we characterize the expression of Stk11, the protein product of the STK11 gene, in a larger series of pancreatic and biliary neoplasms. First, the specificity of the Stk11 antibody was established in 23 neoplasms (22 IPMNs and 1 biliary adenocarcinoma) with known STK11 gene status. Complete absence of labeling was seen in the neoplastic cells of 3 of the 3 (100%) cases with previously documented biallelic inactivation of the STK11 gene, whereas 16 of the 20 (80%) IPMNs, presumably with at least one wild-type STK11 gene, retained Stk11 expression in the neoplastic cells. The marked decrease or absence of Stk11 expression in four neoplasms with wild-type STK11 suggests that additional mechanisms may account for the lack of Stk11 expression. Subsequently, to further evaluate Stk11 expression in pancreatic and biliary neoplasms, tissue microarrays (TMAs) were constructed from a series of nearly 100 ductal adenocarcinomas and biliary neoplasms. Stk11 expression was lost in 4 of the 56 (7%) pancreatic adenocarcinomas and 1 of the 38 (2.6%) biliary cancers by immunohistochemistry; the absence of labeling was confirmed by repeated immunohistochemical labeling of complete tissue sections for the same cases. Thus, Stk11 expression is abrogated in a small proportion of pancreatic and biliary neoplasms. The inactivation of Stk11 in 27% (6/22) of IPMNs versus 7% (4/56) of pancreatic adenocarcinomas suggests genetic disparities in the pathogenesis of these closely related neoplasms. Immunohistochemical analysis for Stk11 expression may be a valid surrogate for genetic analysis of STK11 gene mutations in cancers.
KW - Biliary cancer
KW - IPMN
KW - Immunohistochemistry
KW - LKB1
KW - Pancreatic cancer
KW - Peutz-Jeghers Syndrome
KW - STK11
KW - TMA
KW - Tumor-suppressor gene
UR - http://www.scopus.com/inward/record.url?scp=0038107613&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038107613&partnerID=8YFLogxK
U2 - 10.1097/01.MP.0000075645.97329.86
DO - 10.1097/01.MP.0000075645.97329.86
M3 - Article
C2 - 12861065
AN - SCOPUS:0038107613
VL - 16
SP - 686
EP - 691
JO - Modern Pathology
JF - Modern Pathology
SN - 0893-3952
IS - 7
ER -