• Information
  1. Utility
  2. Human Chorionic Gonadotropin
  3. Protein CA15-3
  4. Protein CA27.29
  5. Prostate Specific Antigen
  6. Protein CA 125
  7. Protein CA 19-9
  8. Carcinoembryonic Antigen
  9. alpha Fetoprotein
  10. Nuclear Matrix Protein 22
  11. Markers By Tumor Type

A. Utility [1,2]

1. Screening and Diagnosis of Cancer (Ca)
   1. Most are poor screening tools at present due to lack of specificity
   2. Helpful for initial predictions in identifying masses, particularly in high risk persons
2. Prognosis
3. Monitor regression with therapy
4. Detect Relapse

B. Human Chorionic Gonadotropin (HCG)

1. Trophoblastic tumors
   1. Choriocarcinoma
   2. Non-seminiferous Germ Tumors
   3. Seminiferous Germ Tumors, 10%
2. False Positives: Pregnancy and Ectopic Pregnancy
3. Serum half life is 1 day

C. Protein CA15-3

1. Breast Ca (most specific marker to date)
2. Benign Breast and Liver Disease may also elevate level
3. Clinical trials ongoing to access sensitivity, specificity

D. Protein CA27.29

1. CA27.29 antigen is a glycoprotein mainly found on breast Ca cells
2. CA27.29 can be measured with Truquant BR® blood test and predicts disease recurrence
3. CA27.29 turns out to be an epitope of CA15-3
4. Test is now FDA approved for detection of recurrent disease

E. Prostate Specific Antigen (PSA) [3]

1. Standard Analysis use the following interpretations:
   1. Levels 1-4ng/mL benign
   2. Levels 4-10ng/mL indeterminent (~25% are found to have cancer on biopsy)
   3. Levels >10ng/mL usually indicate locally spread or metastatic disease
2. Age and prostate volume adjustments more specific for Ca
3. Prostatic acid phosphatase is used only to monitor therapy, surgical resection, relapse

F. Protein CA 125

1. Ovarian Carcinoma (~80%)
2. Level of CA 125 is elevated in ~1% of normal women
3. Utility probably restricted to patients with pelvic mass
4. Some breast tumors express this antigen

G. Protein CA 19-9

1. Colorectal Ca: 20% of cases
2. Gastric Ca: 42% of cases
3. Hepatocellular Ca: 30% of cases
4. Pancreatic Ca: 85% of cases
   1. Positive predictive value ~60%
   2. Negative predictive value ~92%
5. This is a mucin detection assay detecting a non-universal epitope
6. CAM 17.1 assay is a new type of detection assay [4]

H. Carcinoembryonic Antigen (CEA)

1. Colon Ca
   1. Use to monitor therapy
   2. Detect relapse
2. May be elevated in any intestinal pathology
3. Certain teratomas
4. Lung and other adenocarcinomas [5]
5. CEA-scan (radioactive antibody) is near approval for detection of colon CA

I. alpha Fetoprotein (AFP)

1. Hepatocellular Ca
   1. Level >20ng/mL is suggestive; level >500ng/mL has ~100% positive predictive value
   2. Screen for Hepatitis B and C viruses
   3. Use to screen patients with cirrhosis (any cause) once per year
2. Teratoma
   1. Non-seminiferous only
   2. Positive AFP rules out seminomatous teratoma
3. Serum T1/2 ~ 5 days

J. Nuclear Matrix Protein 22 (NMP22) [6,7]

1. Nuclear matrix protein 22 shed in urine in bladder cancer
2. Sensitivity ~50% and specificity ~85% in voided urine sample
3. Has detected cancers that were missed on initial cystoscopy
4. Superior to voided urine cytology for recurrence detection
5. When combined with cystoscopy, improved detection of recurrent early stage disease
6. NMP22 tumor marker assessed with point-of-care test on voided urine sample

K. Markers By Tumor Type

1. Breast Cancer
   1. Common: CEA, CA15-3, CA 27.29
   2. CA549, CA M26, M29, MCA
   3. Estrogen and progesterone receptors
2. Colorectal Cancer
   1. Common: CEA
   2. CA 19-9
   3. CA195, CA72-4, CA50
3. Ovarian Cancer
   1. CA 125
   2. Galactosyl Transferase
4. Lung Cancer (Small Cell)
   1. NSE
   2. CK-BB
5. Pancreatic (and Gastric) Cancers
   1. Common: CA 19-9 and CEA
   2. CA195, CA72-4, CA50
6. Prostate: PSA
7. Liver
   1. AFP
   2. CEA
8. Neuroblastoma
   1. VMA
   2. Catecholamines
   3. Norepinephrine
9. Thyroid
   1. Thyroglobulin
   2. Calcitonin
   3. Thyroid transcription factor 1
10. Head and Neck: SOC
11. Bone: alkaline phosphatase
12. Neuroendocrine Markers [5]
    1. Neuron-specific enolase
    2. Synaptophysin
    3. Chromogranin

References

1. Perkins GL, Slater ED, Sanders GK, Prichard JG. 2003. Am Fam Phys. 68(6):1075
2. Bates SE. 1991. Ann Intern Med. 115(8):623
3. Frydenbrg M, Stricker PD, Kaye KW. 1997. Lancet. 349:1681
4. Yiannakou JY, Newland P, Calder F, et al. 1997. Lancet. 349:389
5. Lynch TJ, Wright CD, Choi NC, et al. 2004. NEJM. 351(8):809 (Case Record)
6. Grossman HB, Messing E, Soloway M, et al. 2005. JAMA. 293(7):810
7. Grossman HB, Soloway M, Messing E, et al. 2006. JAMA. 295(3):299