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Int J Clin Exp Pathol 2010;3(1):47-55
Original Article
The Developmental Transcription Factor Gata4 is Overexpressed in Pancreatic
Ductal Adenocarcinoma
Matthew S. Karafin, Christopher T. Cummings, Baojin Fu, and Christine A. Iacobuzio-Donahue
Departments of Pathology1 and Oncology2, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions,
Baltimore MD
Received July 16, 2009; accepted August 16, 2009; Available online August 30, 2009
Abstract: GATA4 is a transcription factor that plays a role in regulating the normal development of many mesoderm and endoderm derived
tissues, including the pancreas. Silencing of GATA4 mRNA expression by promoter methylation has been implicated in carcinogenesis of the
ovary, lung and colorectum. By contrast, GATA4 mRNA expression is upregulated in pancreatic cancer cell lines and tissues. To further clarify
the relationship of GATA4 to pancreatic cancer, we immunolabeled 90 samples of pancreatic ductal adenocarcinoma using a GATA4 specific
monoclonal antibody. Both the intensity and percent of labeling was recorded for each carcinoma and correlated to the clinicopathologic
features available for each patient. Samples of normal adult (n=26) and fetal pancreatic tissue (n=8) were also immunolabeled for comparison
to expression patterns in pancreatic carcinoma tissues. Immunolabeling for GATA4 indicated robust nuclear expression in developing acini in
fetal pancreatic tissues, consistent with the role of GATA4 in embryologic development, and in mature pancreatic acinar epithelium.
Immunolabeling for GATA4 was also noted within normal duct epithelial cells, although it was always lesser in intensity than for acinar cell
nuclei in the same section. Positive GATA4 immunolabeling was seen in 61/90 (68%) infiltrating pancreatic cancers of which 27/90 (30%)
showed strong positive labeling. While there was no relationship among GATA4 and patient age, race or pathologic features, we did find a
significant association among strong positive labeling and female gender (p=0.01). These findings support previous studies implicating
GATA4 in pancreatic cancer and offer new avenues for investigation into this aggressive tumor type. (IJCEP907005).
Key words: pancreatic cancer, transcription factor, embryology, development
Full text PDF
Address all correspondence to:
Christine A. Iacobuzio-Donahue, MD, PhD
Departments of Pathology and Oncology
The Sol Goldman Pancreatic Cancer Research Center
Johns Hopkins Medical Institutions
Baltimore, MD, USA
E-mail: ciacobu@jhmi.edu
Original Article
The Developmental Transcription Factor Gata4 is Overexpressed in Pancreatic
Ductal Adenocarcinoma
Matthew S. Karafin, Christopher T. Cummings, Baojin Fu, and Christine A. Iacobuzio-Donahue
Departments of Pathology1 and Oncology2, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions,
Baltimore MD
Received July 16, 2009; accepted August 16, 2009; Available online August 30, 2009
Abstract: GATA4 is a transcription factor that plays a role in regulating the normal development of many mesoderm and endoderm derived
tissues, including the pancreas. Silencing of GATA4 mRNA expression by promoter methylation has been implicated in carcinogenesis of the
ovary, lung and colorectum. By contrast, GATA4 mRNA expression is upregulated in pancreatic cancer cell lines and tissues. To further clarify
the relationship of GATA4 to pancreatic cancer, we immunolabeled 90 samples of pancreatic ductal adenocarcinoma using a GATA4 specific
monoclonal antibody. Both the intensity and percent of labeling was recorded for each carcinoma and correlated to the clinicopathologic
features available for each patient. Samples of normal adult (n=26) and fetal pancreatic tissue (n=8) were also immunolabeled for comparison
to expression patterns in pancreatic carcinoma tissues. Immunolabeling for GATA4 indicated robust nuclear expression in developing acini in
fetal pancreatic tissues, consistent with the role of GATA4 in embryologic development, and in mature pancreatic acinar epithelium.
Immunolabeling for GATA4 was also noted within normal duct epithelial cells, although it was always lesser in intensity than for acinar cell
nuclei in the same section. Positive GATA4 immunolabeling was seen in 61/90 (68%) infiltrating pancreatic cancers of which 27/90 (30%)
showed strong positive labeling. While there was no relationship among GATA4 and patient age, race or pathologic features, we did find a
significant association among strong positive labeling and female gender (p=0.01). These findings support previous studies implicating
GATA4 in pancreatic cancer and offer new avenues for investigation into this aggressive tumor type. (IJCEP907005).
Key words: pancreatic cancer, transcription factor, embryology, development
Full text PDF
Address all correspondence to:
Christine A. Iacobuzio-Donahue, MD, PhD
Departments of Pathology and Oncology
The Sol Goldman Pancreatic Cancer Research Center
Johns Hopkins Medical Institutions
Baltimore, MD, USA
E-mail: ciacobu@jhmi.edu
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