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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

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
Leading causes of death in the United States

Source: http://www.cdc.gov (1995 data)

causes of cancer deaths in the united states
Causes of cancer deaths in the United States

Source: CA Cancer J Clin 46:1996

incidence and mortality of gi pancreatic tumors 1996 estimates
Incidence and mortality of GI/pancreatic tumors (1996 estimates)

Source: CA Cancer J Clin 46:1996

colorectal cancer
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)
chemical markers of colorectal cancer
Chemical markers of colorectal cancer
  • Carcinoembryonic antigen (CEA)
  • High molecular weight alkaline phosphatase
  • Mucin CA M43
  • K-ras mutation
carcinoembryonic antigen
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
chemical markers of colorectal cancer8
Chemical markers of colorectal cancer
  • Carcinoembryonic antigen (CEA)
  • High molecular weight alkaline phosphatase
  • Mucin CA M43
  • K-ras mutation
high molecular weight alkaline phosphatase
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%
chemical markers of colorectal cancer10
Chemical markers of colorectal cancer
  • Carcinoembryonic antigen (CEA)
  • High molecular weight alkaline phosphatase
  • Mucin CA M43
  • K-ras mutation
ca m43
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
chemical markers of colorectal cancer12
Chemical markers of colorectal cancer
  • Carcinoembryonic antigen (CEA)
  • High molecular weight alkaline phosphatase
  • Mucin CA M43
  • K-ras mutation
k ras mutation
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
pancreatic cancer
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%
ca 19 9
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
slide18
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
cam 17 1
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
stomach cancer
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)
he uses statistics as a drunken man uses lamp posts for support rather than illumination

“He uses statistics as a drunken man uses lamp posts -- for support rather than illumination.”

Andrew Lang (1844-1912)