Differential expression of chemokines in normal pancreas and in chronic pancreatitis

AbstractDysregulated expression of the secretory protein renalase (RNLS) can promote pancreatic ductal adenocarcinoma (PDAC) growth in animal models. We characterized RNLS expression in premalignant and malignant PDAC tissue and investigated whether plasma RNLS levels corresponded to clinical PDAC characteristics. RNLS immunohistochemistry was used to determine the presence and distribution of RNLS in normal pancreas, chronic pancreatitis, PDAC precursor lesions, and PDAC tissues. Associations between pretreatment plasma RNLS and PDAC clinical status were assessed in patients with varied clinical stages of PDAC and included tumor characteristics, surgical resection in locally advanced/borderline resectable PDAC, and overall survival. Data were retrospectively obtained and correlated using non-parametric analysis. Mild to no RNLS was detected by histochemistry in the normal pancreas in the absence of abdominal trauma. In chronic pancreatitis, RNLS immunoreactivity localized to peri-acinar spindle-shaped cells in some samples. It was also widely present in PDAC precursor lesions and PDAC tissue. Among 240 patients with PDAC, elevated plasma RNLS levels were associated with worse tumor characteristics, including greater angiolymphatic invasion (80.0% vs. 58.1%, p = 0.012) and greater node positive disease (76.5% vs. 56.5%, p = 0.024). Overall survival was worse in patients with high plasma RNLS levels with median follow-up of 27.70 months vs. 65.03 months (p < 0.001). RNLS levels also predicted whether patients with locally advanced/borderline resectable (LA/BR) PDAC underwent resection (AUC 0.674; 95%CI 0.42-0.82, p = 0.04). Overall tissue RNLS was increased in both premalignant and malignant PDAC tissues compared to normal pancreas. Elevated plasma RNLS levels were associated with advanced tumor characteristics, decreased overall survival, and reduced resectability in patients with LA/BR PDAC. These studies show that RNLS levels are increased in premalignant pancreatic tissues and that its levels in plasma correspond to the clinical behavior of PDAC.

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Immunohistochemical Detection of the β4 Integrin Subunit in Pancreatic Adenocarcinoma

Journal of Histochemistry & Cytochemistry ◽

10.1369/jhc.4b6522.2005 ◽

2005 ◽

Vol 53 (6) ◽

pp. 799-801 ◽

Cited By ~ 19

Author(s):

Brianna Gleason ◽

Brian Adley ◽

M. Sambasiva Rao ◽

Leslie K. Diaz

Keyword(s):

Pancreatic Cancer ◽

Chronic Pancreatitis ◽

Ductal Adenocarcinoma ◽

Integrin Subunit ◽

Immunohistochemical Detection ◽

Normal Pancreas ◽

Subunit Protein ◽

Archival Material ◽

Immunohistochemical Methods ◽

Β4 Integrin

The expression of the β4 integrin subunit protein in pancreatic cancer was investigated using routine immunohistochemical methods on paraffin-embedded archival material. Forty-eight cases of pancreatic ductal adenocarcinoma were immunostained with a monoclonal antibody to the β4 integrin subunit, and the extent of staining was compared with that seen in non-cancerous pancreatic tissues, including 15 separate cases of chronic pancreatitis and 6 sections from normal pancreas. We found that the β4 integrin subunit protein was overexpressed in the majority of pancreatic carcinoma cases tested, whereas chronic pancreatitis and normal pancreas did not display substantial levels of expression.

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Sa1543 A New EUS Imaging Diagnosis for Mild Chronic Pancreatitis: A Pilot Study of Differential Diagnosis Between Mild Chronic Pancreatitis and Normal Pancreas Based on the Quantitative Analysis With New Technology Using Raw Image

Gastrointestinal Endoscopy ◽

10.1016/j.gie.2012.04.332 ◽

2012 ◽

Vol 75 (4) ◽

pp. AB196 ◽

Cited By ~ 1

Author(s):

Atsushi Irisawa ◽

Goro Shibukawa ◽

Tadayuki Takagi ◽

Tsunehiko Ikeda ◽

Rei Suzuki ◽

...

Keyword(s):

Differential Diagnosis ◽

Chronic Pancreatitis ◽

Quantitative Analysis ◽

Pilot Study ◽

New Technology ◽

Normal Pancreas ◽

Imaging Diagnosis

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Differences in Immunohistochemical Expression of Xenobiotic-Metabolizing Enzymes Between Normal Pancreas, Chronic Pancreatitis and Pancreatic Cancer

Toxicologic Pathology ◽

10.1080/01926230390226041 ◽

2003 ◽

Vol 31 (5) ◽

pp. 506-513 ◽

Cited By ~ 14

Author(s):

Jens Standop ◽

Matthias Schneider ◽

Alexis Ulrich ◽

Markus W. Büchler ◽

Parviz M. Pour

Keyword(s):

Pancreatic Cancer ◽

Cytochrome P450 ◽

Chronic Pancreatitis ◽

Islet Cells ◽

Enzyme System ◽

Normal Pancreas ◽

Immunohistochemical Expression ◽

Metabolizing Enzymes ◽

Pancreatic Diseases ◽

Xenobiotic Metabolizing Enzymes

Metabolic activation of many toxins, carcinogens, drugs, and anti-cancer agents is governed by the cytochrome P450 (CYP) drug-metabolizing enzyme system. To help elucidate the role of this enzyme system in the pathogenesis of chronic inflammatory and malignant pancreatic diseases, we compared the immunohistochemical expression pattern of 8 CYP-enzymes in 24 normal, 20 chronic pancreatitis, and 21 pancreatic cancer specimens using antibodies to CYP 1A1, 1A2, 2B6, 2C8/9/19, 2D6, 2E1, and 3A4, and the NADPH cytochrome P450 oxido-reductase (NA-OR). Compared to the normal pancreas, a higher frequency of immunopositivity for CYP 1A2, 2B6, 2C8/9/19, 2D6, and NA-OR was found in chronic pancreatitis, and of all CYPs but 1A2 in pancreatic cancer. On the other hand, CYP 1A1 and 2E1 antibody staining was less frequently observed in chronic pancreatitis. In all specimens with pancreatic polypeptide (PP)-rich regions (pancreas head), more islet cells than ductal and acinar cells were immunopositive. Moreover, the immunoreactivity of islet cells from PP-rich specimens with anti-CYP antibodies was consistently more frequent and intense than in islet cells from PP-poor areas (body and tail). Immunoreactivity for xenobiotic-metabolizing enzymes was frequently observed in the normal pancreas, chronic pancreatitis, and pancreatic cancer, and displayed differences of its frequency and intensity between the 3 groups. Considering immunohistochemical evidence of enzyme expression and pancreatic blood supply together, islet cells appear to be an important and possible early site of CYP-enzyme induction in pancreatic diseases.

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