The Sol Goldman Pancreatic Cancer Research Center


Advances and Discoveries Made at Johns Hopkins


Target of chemopreventive agents (August 2002):
One of the more exciting approaches to saving lives is preventing pancreatic cancer through the use of "chemopreventive" agents. Chemopreventive agents are drugs that are taken regularly and reduce one's risk of cancer. Cox-2 (also known as cyclooxygenase 2) is an enzyme made by cells that is a target for some chemopreventive drugs. In the August issue of the American Journal of Clinical Pathology, Dr. Maitra and colleagues from Johns Hopkins report that cyclooxygenase 2 is expressed (made by) small lesions in the pancreas called "pancreatic intraepithelial neoplasia." This is important because pancreatic intraepithelial neoplasia is believed to be the precursor to pancreatic cancer. The expression of cyclooxygenase 2 in pancreatic intraepithelial neoplasia lesions suggests that cyclooxygenase 2 inhibitors could be used to prevent the development of pancreatic cancer. Further work is needed, but clearly chemopreventive agents, such as cyclooxygenase 2 inhibitors, offer an exciting new approach to fight pancreatic cancer before it develops.

American Journal of Clinical Pathology(Volume 118, pages 194-201)



BRCA2 gene is important in familial pancreatic cancer (July 2002):
Investigators from Johns Hopkins found that 1 in 6 (17%) patients with a very strong family history of pancreatic cancer have inherited ("germline") mutations (changes) in the BRCA2 gene. The BRCA2 is also known as the second breast cancer gene. Although it has been known for years that BRCA2 was important in familial breast cancer, the importance of BRCA2 in familial pancreatic cancer is only now coming to light. Inherited mutations in BRCA2 are particularly common in the Ashkenazi Jewish population. The identification of a gene responsible for the familial aggregation of pancreatic cancer is important because at-risk family members can now be tested to see if they carry this gene.

Cancer Research (Volume 62, pages 3789-93)

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Genetic alterations in solid-pseudopapillary tumors of the pancreas (April 2002):
Solid-pseudopapillary tumors are rare tumors of the pancreas that arise primarily in young women. They have a distinct appearance under the microscope and a much better prognosis than the more common ductal adenocarcinomas of the pancreas. Scientists at Johns Hopkins studied the fundamental genetic (DNA) changes in a series of solid-pseudopapillary tumors of the pancreas and found that they almost all have mutations (DNA changes) in a particular gene called Beta-catenin. By contrast, usual ductal adenocarcinomas of the pancreas almost never have Beta-catenin mutations.

It can sometimes be difficult in a small biopsy or even in a resected specimen to distinguish between the various types of tumors that arise in the pancreas. This discovery suggests that the presence or absence of Beta-catenin mutations in a tumor can be used to distinguish between solid-pseudopapillary tumors (which have a very good prognosis) and usual ductal adenocarcinomas (which do not have a good prognosis).

American Journal of Pathology (Volume 160, pages 1361-1369)

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Genetic alterations in acinar cell carcinomas of the pancreas (March 2002):
Acinar cell carcinomas are rare malignant tumors of the pancreas. They are microscopically different from the more common "ductal adenocarcinomas" of the pancreas. The fundamental DNA (genetic) changes that underlie the development of acinar cell carcinomas have not yet been elucidated. Scientists at Johns Hopkins studied 21 acinar cell carcinomas of the pancreas and found a distinct pattern of DNA changes in these tumors. These DNA changes included loss of chromosome arm 11p and changes in the "APC/beta-catenin pathway." These results indicate that acinar cell carcinomas are genetically distinct from pancreatic ductal adenocarcinomas, but some cases contain genetic alterations common to another rare tumor type in the pancreas called "pancreatoblastomas." An understanding of the variants of pancreatic cancer helps us understand why some tumors occur in different patients. In addition, it should form a basis for targeting specific therapies to specific tumor types.

American Journal of Pathology (Volume 160,pages 953-962)

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Discovery of a panel of genes made by pancreatic cancers (February and March 2002):
Scientists at Johns Hopkins used two different techniques―"SAGE" and gene chips―to discover a panel of over 100 genes that are made at high levels in pancreatic cancer but not in normal tissues. They used the recently developed technology "SAGE" (serial analysis of gene expression) technology as well as cutting-edge gene chips. These technologies were applied to a panel of pancreatic cancers and normal pancreas cells and the investigators discovered a novel panel of over genes that appear to be made ("expressed") at high levels in pancreatic cancer. Several genes that may be involved in the fundamental nature of malignant changes in pancreatic ductal epithelium were identified. Some genes, such as S100A4, prostate stem cell antigen, and carcinoembryonic antigen-related cell adhesion molecule 6, suggest potential use as diagnostic markers. Others suggest potential novel therapeutic targets. These two studies provide insight into the fundamental nature of pancreatic cancer and each of the more than 100 genes discovered to be made at high levels in pancreatic cancer may serve as a new marker for the early detection of pancreatic cancer, or as a target for the development of new chemotherapies.

Cancer Research (Volume 62, pages 819-826)
American Journal of Pathology (Volume 160, pages 1239-1249)

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Target of chemopreventive agents made in pancreatic cancer precursors:
One of the more exciting approaches to saving lives that would otherwise be lost to pancreatic cancer is preventing pancreatic cancer through the use of "chemopreventive" agents. Chemopreventive agents are drugs that are taken regularly and reduce one's risk of cancer. For example, a recent study suggested that regular aspirin use may reduce the risk of developing pancreatic cancer. Cox-2 (also known as cyclooxygenase 2) is an enzyme made by cells that is a target for some chemopreventive drugs. In the August issue of the American Journal of Clinical Pathology Dr. Maitra and colleagues from Johns Hopkins report that cyclooxygenase 2 is expressed (made by) small lesions in the pancreas called "pancreatic intraepithelial neoplasia".

Why is this important?
Pancreatic intraepithelial neoplasia is believed to be the precursor to pancreatic cancer. The expression of cyclooxygenase 2 in pancreatic intraepithelial neoplasia lesions suggests that cyclooxygenase 2 inhibitors could be used to prevent the development of pancreatic cancer. Further work is needed, but clearly chemopreventive agents, such as cyclooxygenase 2 inhibitors, offer an exciting new approach to fight pancrewatic cancer before it develops.

Am J Clin Pathol 2002 Aug;118(2):194-201.

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BRCA2 gene important in familial pancreatic cancer
In the July 2002 issue of Cancer research K. Murphy and colleagues from Johns Hopkins reported that 1 in 6 (17%) patients with a very strong family history of pancreatic cancer have inherited ("germline") mutations (changes) in the BRCA2 gene. The BRCA2 is also known as the second breast cancer gene. Although it has been known for years that BRCA2 was important in familial breast cancer, the importance of BRCA2 in familial pancreatic cancer is only now coming to light. Inherited mutations in BRCA2 are particularly common in the Askenazi Jewish population.

Why is this important?
The identification of a gene responsible for the familial aggregation of pancreatic cancer is important because at-risk family members can now be tested to see if they carry this gene. If you are interested in learning more about genetic testing visit: http://www.pbs.org/gene/findout/3_findout.html. To find a genetic counselor near you visit: http://www.nsgc.org/. To join the National Familial Pancreas Tumor Registry at Johns Hopkins, contact Alison Klein: aklein1@jhmi.edu.

Cancer Res 2002 Jul 1;62(13):3789-93.

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Genetic alterations in solid-pseudopapillary tumors of the pancreas:
Solid-pseudopapillary tumors are rare tumors of the pancreas that arise primarily in young women. They have a distinct appearance under the microscope and a much much better prognosis than the more common ductal adenocarcinomas of the pancreas. Dr. Susan Abraham and colleagues studied the fundamental genetic (DNA) changes in a series of solid-pseudopapillary tumors of the pancreas and found that they almost all have mutations (DNA changes) in a particular gene called Beta-catenin. By contrast, usual ductal adenocarcinomas of the pancreas almost never have Beta-catenin mutations.

Why is this important?
It can sometimes be difficult in a small biopsy or even in a resected specimen to distinguish between the various types of tumors that arise in the pancreas. This discovery by Dr. Abraham suggests that the presence or absence of Beta-catenin mutations in a tumor can be used to distinguish between solid-pseudopapillary tumors (which have a very good prognosis) and usual ductal adenocarcinomas (which do not have a good prognosis)

Am J Pathol 2002 Apr;160(4):1361-9

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Genetic alterations in acinar cell carcinomas of the pancreas
Acinar cell carcinomas are rare malignant tumors of the pancreas. They are microscopically different from the more common "ductal adenocarcinomas" of the pancreas. The fundamental DNA (genetic) changes that underlie the development of acinar cell carcinomas have not yet been elucidated. Scientists at Johns Hopkins studied 21 acinar cell carcinomas of the pancreas and found a distinct pattern of DNA changes in these tumors. These DNA changes included loss of chromosome arm 11p and changes in the "APC/beta-catenin pathway". These results indicate that acinar cell carcinomas are genetically distinct from pancreatic ductal adenocarcinomas, but some cases contain genetic alterations common to another rare tumor type in the pancreas called "pancreatoblastomas".

Why is this important?
An understanding of the variants of pancreatic cancer helps us understand why some tumors occur in different patients. In addition, it should form a basis for targeting specific therapies to specific tumor types.

Am J Pathol 2002 Mar;160(3):953-62

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Discovery of a panel of genes made by pancreatic cancers
Scientists at Johns Hopkins used two different techniques- "SAGE" and gene chips to discover a panel of over 100 genes that are made at high levels in pancreatic cancer but not in normal tissues. Dr. Ryu and colleagues used the recently developed technology "SAGE" (serial analysis of gene expression) technology while Dr. Christine Iacobuzio-Donahue and colleagues used gene chips. These technologies were applied to a panel of pancreatic cancers and normal pancreas cells and Drs. Ryu and Iacobuzio-Donahue discovered a novel panel of over genes that appear to be made ("expressed") at high levels in pancreatic cancer. Several genes that may be involved in the fundamental nature of malignant changes in pancreatic ductal epithelium were identified. Some genes, such as S100A4, prostate stem cell antigen, carcinoembryonic antigen-related cell adhesion molecule 6, and mesothelin, suggest potential use as diagnostic markers. Others suggest potential novel therapeutic targets.

Why is this important?
These two studies provide insight into the fundamental nature of pancreatic cancer and each of the more than 100 genes discovered to be made at high levels in pancreatic cancer may serve as a new marker for the early detection of pancreatic cancer, or as a target for the development of new chemotherapies.

Cancer Res 2002 Feb 1;62(3):819-26
Am J Pathol. 2002 Apr;160(4):1239-49

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Extent of surgery for pancreatic cancer:
The extent of surgery appropriate for patients with pancreatic cancer has long been debated. Some surgeons perform a "standard" whipple resection (also called a standard pancreaticoduodenectomy) while others have suggested that more extensive ("radical") surgery is needed. Dr. C. Yeo and colleagues from Johns Hopkins therefore performed a randomized study of 294 patients surgically treated at Johns Hopkins. Patients were randomized to either a "standard" whipple or a more "radical" whipple procedure. In the September 2002 issue of the Annals of Surgery, Dr. Yeo reports that the radical (extended) whipple can be performed with similar mortality (death rate) but some increased morbidity (complications) compared to standard whipple. No long-term benefit was found in the more radical surgery.

Why is this important?
This study suggests that although more radical surgery can be performed safely, it may not provide any long-term benefits.

Ann Surg 2002 Sep;236(3):355-68

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