Abstract
BackgroundElevated serum concentrations of M2-pyruvate kinase (M2-PK) correlate with poor prognosis in patients with pancreaticobiliary and duodenal cancer, but the expression of M2-PK in formalin-fixed pancreatic tissue is unknown. We aimed to characterise the immunohistochemical expression of M2-PK in archived specimens of pancreaticobiliary and duodenal cancers, premalignant lesions, chronic pancreatitis, and normal pancreas.MethodsImmunohistochemical staining was performed with mouse anti-M2-PK monoclonal antibody (clone DF-4) at an optimal dilution of 1:25 on tissue microarrays constructed from formalin-fixed paraffin-embedded pancreatic tissue of 126 consecutive patients undergoing pancreatic resections between June 2001 and June 2006. 104 underwent resection for cancer and 22 for chronic pancreatitis. 78 specimens of chronic pancreatitis tissue were obtained adjacent to areas of cancer. Normal pancreatic tissue was obtained from the resection specimens in a total of 30 patients. Metastatic tumours in 61 regional lymph nodes from 61 patients were also studied. A further 11 premalignant pancreaticobiliary and duodenal lesions were studied. M2-PK expression was quantified with the immunohistochemical score (IHS; Range 0-12).ResultsBenign non-ductal tissue in chronic pancreatitis and normal pancreas showed variable expression of M2-PK (IHS = 1 in 25%, IHS = 2-3 in 40%, IHS>3 in 40%). Benign pancreatic ductal epithelium, all primary pancreaticobiliary and duodenal premalignant lesions and cancers (and lymph node metastasis) showed complete lack of expression (IHS = 0).ConclusionComplete lack of M2-PK expression was observed in benign pancreatic ducts, premalignant lesions and cancer. M2-PK is present only in benign non-ductal epithelium in normal pancreas and peri-tumoural tissue.
Highlights
Elevated serum concentrations of M2-pyruvate kinase (M2-PK) correlate with poor prognosis in patients with pancreaticobiliary and duodenal cancer, but the expression of M2-PK in formalin-fixed pancreatic tissue is unknown
Tumour M2PK has been detected in normal fresh colonic epithelium, but increases greatly in colonic adenocarcinomas, and plasma concentrations correlate with tumour load in patients with lung cancer [1,3]
Normal pancreatic tissue was obtained from the resection specimens, adjacent to areas of cancer or chronic pancreatitis
Summary
Elevated serum concentrations of M2-pyruvate kinase (M2-PK) correlate with poor prognosis in patients with pancreaticobiliary and duodenal cancer, but the expression of M2-PK in formalin-fixed pancreatic tissue is unknown. The predominance of the inactive dimeric form in tumour cells leads to an accumulation of all phosphometabolites preceding pyruvate kinase in the glycolytic pathway, such as phosphoenolpyruvate, glycerate 3-phosphate, glyceraldehyde 3- phosphate, fructose 1,6-bisphosphate, ribose-5 phosphate and 5'-ribose-pyrophosphate. These are available as precursors for synthesis of nucleic acids, amino acids and phospholipids [5,6]. This switch in metabolism may allow tumour cells to invade areas with low concentrations of oxygen and glucose. Tumour M2-PK has been shown to be measurable in plasma, and in faeces, leading to an interest in its potential as a metabolic marker for the screening of patients at increased risk of colorectal and gastric cancer [8,9]
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