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Soluble chemical markers of gastrointestinal and pancreatic tumors

Soluble chemical markers of gastrointestinal and pancreatic tumors. Roger L. Bertholf, Ph.D. Associate Professor of Pathology University of Florida Health Science Center/Jacksonville. Leading causes of death in the United States. Source: http://www.cdc.gov (1995 data).

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Soluble chemical markers of gastrointestinal and pancreatic tumors

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  1. Soluble chemical markers of gastrointestinal and pancreatic tumors Roger L. Bertholf, Ph.D. Associate Professor of Pathology University of Florida Health Science Center/Jacksonville

  2. Leading causes of death in the United States Source: http://www.cdc.gov (1995 data)

  3. Causes of cancer deaths in the United States Source: CA Cancer J Clin 46:1996

  4. Incidence and mortality of GI/pancreatic tumors (1996 estimates) Source: CA Cancer J Clin 46:1996

  5. Colorectal cancer • Vast majority of cases are adenocarcinomas • Begins with adenomatous polyps • Molecular biology • Point mutations in ras proto-oncogene on chromosome 12 • p53 deletion (chromosome 17) • “DCC” gene deletion (chromosome 18) • “MCC” gene mutation (chromosome 5) • “APC” gene mutation (chromosome 5)

  6. Chemical markers of colorectal cancer • Carcinoembryonic antigen (CEA) • High molecular weight alkaline phosphatase • Mucin CA M43 • K-ras mutation

  7. Carcinoembryonic antigen • Oncofetal antigen expressed in gut, pancreas, and liver • MW 150-300 kD; 50% carbohydrate • Normally, production disappears after birth • Elevated in 60-90% of colorectal cancers • False elevations due to cirrhosis, emphysema, colitis • Most useful for clinical staging, detecting recurrence

  8. Chemical markers of colorectal cancer • Carcinoembryonic antigen (CEA) • High molecular weight alkaline phosphatase • Mucin CA M43 • K-ras mutation

  9. High molecular weight alkaline phosphatase • Also called the “fast liver” fraction • Is more sensitive for cholestasis than liver ALP • In patients with histologically-verified colorectal cancers: • Sensitivity = 63% • Specificity = 89% • In conjunction with CEA • Sensitivity = 72% • Specificity = 87%

  10. Chemical markers of colorectal cancer • Carcinoembryonic antigen (CEA) • High molecular weight alkaline phosphatase • Mucin CA M43 • K-ras mutation

  11. CA M43 • Mucin antigen • Using a two-site solid phase immunoassay: • Sensitivity = 42% • Specificity = 97% • Positive predictive value = 98% • In combination with CEA, sensitivity is slightly improved

  12. Chemical markers of colorectal cancer • Carcinoembryonic antigen (CEA) • High molecular weight alkaline phosphatase • Mucin CA M43 • K-ras mutation

  13. K-ras mutation • Point mutations in the ras family of oncogenes have been described in several malignancies • K-ras mutations at codons 12 and 13 • Most common mutation is Gly-12 to Val-12 • Found in 39-47% of colorectal tumors • Method improvements • Competitive allele-specific oligonucleotide hybridization • Mutant-enriched PCR

  14. Pancreatic cancer • 90% are exocrine, most commonly in the head of the organ • 75% of ductal adenocarcinomas secrete mucin • Clinically silent until it reaches advanced stage • Lung, liver metastases • One-year survival is 8-10% • Five-year survival is 2%

  15. Chemical markers of pancreatic cancer • CA 19-9 • TPS • CAM 17.1

  16. CA 19-9 • Sialylated Lexa • Secreted by gastric, colonic, endometrial, and salivary epithelia • Lea-b- individuals (5%) do not make Ca 19-9 • Clinical performance • Sensitivity = 80% • Specificity = 60-100% (depending on control group) • Low positive predictive value in a screening scenario

  17. Chemical markers of pancreatic cancer • CA 19-9 • TPS • CAM 17.1

  18. TPS • Specific epitope of tissue polypeptide antigen (TPA) • Nonspecific marker of cellular proliferation • Sensitivity is nearly 100% for detecting pancreatic cancer • Specificity, as expected, is low

  19. Chemical markers of pancreatic cancer • CA 19-9 • TPS • CAM 17.1

  20. CAM 17.1 • Immunoglobulin M antibody with high specificity for intestinal mucus • Epitope is a sialylated blood group antigen (probably I) • Sensitivity = 67% in patients with diagnosed pancreatic cancer (correlated with stage) • Specificity • 100% in healthy volunteers • 80% in gastric cancer patients

  21. Stomach cancer • At one time, the most common cause of cancer death in men • Death rate in U.S. has dropped nearly 80% since 1930 • Reason for decline is unknown • 95% are adenocarcinoma originating in mucous cells • Most are discovered after penetrating into the muscularis • Metastases are common • 20% ten-year survival if advanced • “Early gastric cancer” (confined to mucosa or submucosa)

  22. “He uses statistics as a drunken man uses lamp posts -- for support rather than illumination.” Andrew Lang (1844-1912)

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