| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 152, 1501-1507, Copyright © 1998 by American Society for Investigative Pathology
REGULAR ARTICLES |
M Goggins, GJ Offerhaus, W Hilgers, CA Griffin, M Shekher, D Tang, TA Sohn, CJ Yeo, SE Kern and RH Hruban
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
The clinical and pathological features of carcinomas of the pancreas with DNA replication errors (RER+) have not been characterized. Eighty- two xenografted carcinomas of the pancreas were screened for DNA replication errors using polymerase chain reaction amplification of microsatellite markers. Cases with microsatellite instability in at least two markers of a minimum of five tested were considered RER+. RER status was correlated with histological appearance, karyotype of the carcinomas when available, K-ras mutational status, and patient outcome. Three (3.7%) of the eighty-two carcinomas were RER+. In contrast to typical gland-forming adenocarcinomas of the pancreas, all three RER+ carcinomas were poorly differentiated and had expanding borders and a prominent syncytial growth pattern. Neither a Crohn's- like lymphoid infiltrate nor extracellular mucin production were prominent. Ductal adenocarcinomas of the pancreas typically contain a mutant K-ras gene, yet all three RER+ carcinomas had wild-type K-ras. One of the three RER+ carcinomas was karyotyped and showed a near diploid pattern. All three of the RER+ tumors were removed via Whipple resection. One of the three patients is free of disease 16 months after pancreaticoduodenectomy, one is alive and free of tumor at 52 months but developed two colon carcinomas during this period, and the third died of pancreatic cancer at 4 months. None of the three patients had a family history of colorectal carcinoma. A review of the K-ras wild-type carcinomas in a previously characterized series of pancreatic carcinomas with known K-ras mutational status identified two additional cancers with poor differentiation, a syncytial growth pattern, and pushing borders. Both of the cancers were diploid and both patients were longterm survivors (over 5 years). The inclusion of such patients in previous prognostic studies of pancreas cancer may explain the failure of histological grade to be a predictor of prognosis. These data suggest that DNA replication errors occur in a small percentage of resected carcinomas of the pancreas and that wild-type K-ras gene status and a medullary phenotype characterized by poor differentiation, and expanding pattern of invasion, and syncytial growth should suggest the possibility of DNA replication errors in carcinomas of the pancreas.
This article has been cited by other articles:
 |
|
 |
|
  G. Feldmann and A. Maitra Molecular Genetics of Pancreatic Ductal Adenocarcinomas and Recent Implications for Translational Efforts J. Mol. Diagn., March 1, 2008; 10(2): 111 - 122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Boyer Arnold and M. Korc Smad7 Abrogates Transforming Growth Factor-{beta}1-mediated Growth Inhibition in COLO-357 Cells through Functional Inactivation of the Retinoblastoma Protein J. Biol. Chem., June 10, 2005; 280(23): 21858 - 21866. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Iacobuzio-Donahue, M. S. van der Heijden, M. R. Baumgartner, W. J. Troup, J. M. Romm, K. Doheny, E. Pugh, C. J. Yeo, M. G. Goggins, R. H. Hruban, et al. Large-Scale Allelotype of Pancreaticobiliary Carcinoma Provides Quantitative Estimates of Genome-Wide Allelic Loss Cancer Res., February 1, 2004; 64(3): 871 - 875. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. S. Calhoun, J. B. Jones, R. Ashfaq, V. Adsay, S. J. Baker, V. Valentine, P. M. Hempen, W. Hilgers, C. J. Yeo, R. H. Hruban, et al. BRAF and FBXW7 (CDC4, FBW7, AGO, SEL10) Mutations in Distinct Subsets of Pancreatic Cancer: Potential Therapeutic Targets Am. J. Pathol., October 1, 2003; 163(4): 1255 - 1260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Rashid, T. Ueki, Y.-T. Gao, P. S. Houlihan, C. Wallace, B.-S. Wang, M.-C. Shen, J. Deng, and A. W. Hsing K-ras Mutation, p53 Overexpression, and Microsatellite Instability in Biliary Tract Cancers: A Population-based Study in China Clin. Cancer Res., October 1, 2002; 8(10): 3156 - 3163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-H. Lee, S. C. Abraham, H.-S. Kim, J.-H. Nam, C. Choi, M.-C. Lee, C.-S. Park, S.-W. Juhng, A. Rashid, S. R. Hamilton, et al. Inverse Relationship between APC Gene Mutation in Gastric Adenomas and Development of Adenocarcinoma Am. J. Pathol., August 1, 2002; 161(2): 611 - 618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Nakata, Y. Qing Wang, M. Yashiro, N. Nishioka, H. Tanaka, M. Ohira, T. Ishikawa, H. Nishino, and K. Hirakawa Prognostic Value of Microsatellite Instability in Resectable Pancreatic Cancer Clin. Cancer Res., August 1, 2002; 8(8): 2536 - 2540. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Abraham, T.-T. Wu, R. H. Hruban, J.-H. Lee, C. J. Yeo, K. Conlon, M. Brennan, J. L. Cameron, and D. S. Klimstra Genetic and Immunohistochemical Analysis of Pancreatic Acinar Cell Carcinoma : Frequent Allelic Loss on Chromosome 11p and Alterations in the APC/{beta}-Catenin Pathway Am. J. Pathol., March 1, 2002; 160(3): 953 - 962. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Anderson and J. E. Harris Selected Features of Nonendocrine Pancreatic Cancer Experimental Biology and Medicine, June 1, 2001; 226(6): 521 - 537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yamamoto, F. Itoh, H. Nakamura, H. Fukushima, S. Sasaki, M. Perucho, and K. Imai Genetic and Clinical Features of Human Pancreatic Ductal Adenocarcinomas with Widespread Microsatellite Instability Cancer Res., April 1, 2001; 61(7): 3139 - 3144. [Abstract] [Full Text]
|
|
|
|
|
|
A. C. Tersmette, G. M. Petersen, G. J. A. Offerhaus, F. C. Falatko, K. A. Brune, M. Goggins, E. Rozenblum, R. E. Wilentz, C. J. Yeo, J. L. Cameron, et al. Increased Risk of Incident Pancreatic Cancer Among First-degree Relatives of Patients with Familial Pancreatic Cancer Clin. Cancer Res., March 1, 2001; 7(3): 738 - 744. [Abstract] [Full Text]
|
|
|
|
 |
|
 E EFTHIMIOU, T CRNOGORAC-JURCEVIC, N R LEMOINE, and T A BRENTNALL Inherited predisposition to pancreatic cancer Gut, February 1, 2001; 48(2): 143 - 147. [Full Text] [PDF]
|
|
|
|
|
|
J. Alexander, T. Watanabe, T.-T. Wu, A. Rashid, S. Li, and S. R. Hamilton Histopathological Identification of Colon Cancer with Microsatellite Instability Am. J. Pathol., February 1, 2001; 158(2): 527 - 535. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. C. Slebos, J. A. Hoppin, P. E. Tolbert, E. A. Holly, J. W. Brock, R. H. Zhang, P. M. Bracci, J. Foley, P. Stockton, L. M. McGregor, et al. K-ras and p53 in Pancreatic Cancer: Association with Medical History, Histopathology, and Environmental Exposures in a Population-based Study Cancer Epidemiol. Biomarkers Prev., November 1, 2000; 9(11): 1223 - 1232. [Abstract] [Full Text]
|
|
|
|
|
|
R. H. Hruban, M. Goggins, J. Parsons, and S. E. Kern Progression Model for Pancreatic Cancer Clin. Cancer Res., August 1, 2000; 6(8): 2969 - 2972. [Full Text]
|
|
|
|
|
|
R. E. Wilentz, M. Goggins, M. Redston, V. A. Marcus, N. V. Adsay, T. A. Sohn, S. S. Kadkol, C. J. Yeo, M. Choti, M. Zahurak, et al. Genetic, Immunohistochemical, and Clinical Features of Medullary Carcinoma of the Pancreas : A Newly Described and Characterized Entity Am. J. Pathol., May 1, 2000; 156(5): 1641 - 1651. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ueki, M. Toyota, T. Sohn, C. J. Yeo, J.-P. J. Issa, R. H. Hruban, and M. Goggins Hypermethylation of Multiple Genes in Pancreatic Adenocarcinoma Cancer Res., April 1, 2000; 60(7): 1835 - 1839. [Abstract] [Full Text]
|
|
|
|
|
|
R. E. Wilentz, G. H. Su, J. L. Dai, A. B. Sparks, P. Argani, T. A. Sohn, C. J. Yeo, S. E. Kern, and R. H. Hruban Immunohistochemical Labeling for Dpc4 Mirrors Genetic Status in Pancreatic Adenocarcinomas : A New Marker of DPC4 Inactivation Am. J. Pathol., January 1, 2000; 156(1): 37 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. LONGNECKER Molecular Pathology of Invasive Carcinoma Ann. N.Y. Acad. Sci., June 30, 1999; 880(1): 74 - 82. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
