Blood Tests for Cancer – Tumor Markers

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Blood tests for cancer are also called as Tumor Markers. THey are substances /molecular changes detected in abnormal amounts in the blood produced either by tumor or by the other cells in the body in response to the disease or related to the presence or progress of a tumor

The may be of following types:

  • Diagnostic markers
  • Prognostic markers
  • Therapy selection & response markers
  • Recurrence and metastasis markers

What are Ideal Criterion for Tumor Markers

  • Detectable early in malignant disease
  • Specific for type and site
  • Production by all patients with a specific malignancy
  • Correlates quantitatively with the tumor load, biological behavior, progression
  • Responds rapidly to a change in size
  • Standardized reproducible quantitative assay

None of the Tumor Markers fulfills all the above criterion.

What is the alarming blood level of various Tumor Markers?

Tumor Marker Level above which benign disease is unlikely
CEA >10ng per mL
CA 19.9 >1,000 units per mL
AFP >500 ng per mL.
Β-hCG >30mlU per mL
CA 125 >200 units per mL
PSA >10ng per mL

 

Brief Description of various Blood Tests (Tumor Markers) for Cancer

Prostate Specific Antigen

It is specific for prostate cancer.  Level of more than 4 ng/ml is seen in around 70% of the cases of prostate cancer. But some non-malignant prostate abnormalities could cause PSA elevation. Levels of PSA between 4 to 10 ng/ml could be overlapping for benign and malignant causes. In such cases, PSA velocity and Percent-Free PSA may be helpful to differentiate between the two.

prostate cancer investigations infographic

PSA velocity

It is the change in PSA values over time. It increases the specificity of a single PSA measurement for early cancer detection. Normal levels are around 0.75ng/ml/year. Current recommendation include collection of PSA velocity over not less than 18 months and the use of three values to calculate PSA velocity

Percent Free PSA

It is free PSA, expressed as a ratio with total PSA. Percentage of Free PSA is significantly lower in men with Ca prostate. US FDA approved it for early detection in patients with PSA between 4 & 10 ng/ml.

Benign conditions that may cause false positive PSA elevation are as follows-

  • BPH
  • Lower tract endoscope manipulation
  • Transrectal & transperineal prostate Bx
  • Acute urinary retention
  • Digital rectal examination
  • Prostate massage
  • Acute prostatitis

Clinical applications 

  • Screening – Along with other investigations, it is a part of screening workup for prostate cancer in high risk individuals.
  • Monitoring treatment– It helps in monitoring the response to treatment in prostate cancer. If it is well controlled on a particular therapy, it is an indicator of response to treatment.
  • Detection of early recurrence – If the PSA values start rising after a particular treatment, it may indicate recurrence, and requires imaging for confirmation of the same.

 

Human Chorionic Gonadotrophin (hCG)

It has two subunits, Alpha & Beta Chain. Alpha chain is identical to alpha chain of TSH,FSH, & LH. Serum half-life is 18 to 36 hours. Normal reference range is 0 to 5 IU/L.

Malignant Causes

  • GTN (complete/ partial molar pregnancy, choriocarcinoma)

ovarian cancer blood tests infographic

ovarian cancer germ cell tumors

  • Germ Cell Tumor of Testis

testicular cancer tumor markers infographic

  • Carcinoma of liver, stomach, lung & pancreas.

Non-Malignant Causes (False Positive Elevation)        

  • Ectopic pregnancy
  • Pituitary adenoma
  • Pregnancy
  • After termination of pregnancy
  • Hypogonadal state
  • Marijuana use

Clinical applications 

To monitor the response to treatment and in follow-up for-

  • Gestational trophoblastic tumor
  • With AFP in Non Seminomatous germ cell tumors (NSGCT) of testis, ovary, & other sites

 

Alfa Feto Protein (AFP)

It is a major protein in fetus and is undetectable after birth. Half life of AFP is 5 to 7 days. Normal values is less than 15 ng/mL.

Malignant Causes

  • NSGCT – Testis, ovary, other sites

ovarian cancer blood tests infographic

ovarian cancer germ cell tumors

testicular cancer tumor markers infographic

  • Hepatocellular Carcinoma (HCC)
  • Hepatoblastoma

Non-Malignant Causes (False Positive Elevation) 

  • Hepatitis
  • Cirrhosis
  • Biliary tract obustruction
  • Alcoholic liver disease
  • Ataxia telangiectasia
  • Hereditary tyrosinaemia
  • Wiscott – Aldrich syndrome
  • Physiological-Pregnancy,Infants

Clinical Applications 

Screening

  1. HCC – High risk population (eg; China)
  2. HCC – High risk disease groups (eg; Hemochromatosis, Hepatitis)

Diagnosis

  1. HCC
  2. Hepatoblastoma

Staging and Prognosis

  1. Germ Cell Tumor

 

Carcinoembryonic Antigen (CEA)

It is a 200 kDa. Glycoprotein with physiological function of role in cell adhesion and initiation of apoptosis. It’s half life is 3 days and normal values range from 0-3.5 ng/mL to 0-5.0 ng/mL. It is mainly used in colorectal cancer.

colon cancer investigations infographic

Malignant Causes

  • Gastric Cancer
  • Breast Cancer
  • Lung Cancer
  • Melanoma, pancreatic Cancer

Non-Malignant Causes (False Positive Elevation)    

  • Hepatitis
  • Cirrhosis
  • Alcoholic liver disease
  • Obstructive jaundice
  • Ulcerative colitis
  • Crohn’s disease
  • Pancreatitis
  • Renal disease & Chronic smokers

Clinical Application 

  1. Screening: Due to it’s low sensitivity, it has a limited role in screening of colorectal cancer.
  2. Diagnosis – It may sometimes be normal in cases of colorectal cancer (false negative) and sometimes be elevated in conditions other than colorectal cancer (false positive), as listed above. So these factors limit it’s use as a diagnostic test.
  3. Prognosis – High preoperative CEA value is an indicator of poor prognosis.
  4. Monitoring response to treatment
  5. Detection of early recurrence

 

CA 125

It is a mucin like molecule produced by mesothelial cells of peritoneum and tissues of mullerian origin. It is not found in normal ovary and it’s physiological function is unknown.

Ovarian CA-125 infographic

Malignant Causes

  • Benign:Endometriosis
    • Pelvic inflammatory disease
    • Adenomyosis
    • Benign ovarian neoplasm
    • Functional ovarian cyst
    • Menstruation
    • Uterine Myomata
  • Malignant: Ovarian carcinoma
    • Primary peritoneal carcinoma
    • Endometrial carcinoma

Non-Malignant Causes (False Positive Elevation)  

  • Benign: Acute hepatitis
    • Acute pancreatitis
    • Chronic liver disease
    • Cirrhosis
    • Congestive heart failure
    • Diverticulitis
    • Pericarditis
    • Systemic lupus erythematosus
    • Sarcoidosis

Clinical Application of CA-125

  1. Screening – Due to it’s low sensitivity, it has a limited role in screening of ovarian cancer.
  2. Diagnosis – It may sometimes be normal in cases of ovarian cancer (false negative) and sometimes be elevated in conditions other than ovarian cancer (false positive), as listed above. So these factors limit it’s use as a diagnostic test.
  3. Prognosis – High preoperative CAA-125 value is an indicator of poor prognosis and an independent prediction of survival
  4. Monitoring response to treatment
  5. Detection of early recurrence

 

CA 19-9

It’s half life is 1 to 3 days and normal  range is  0.37 to 0-100 U/L. It is mainly elevated in pancreaticobiliary tumors.

pancreatic cancer investigations

Malignant Causes

  • Pancreatic Cancer – 70-100% cases
  • Hepatocellular Carcinoma
  • Gastric Cancer
  • Colorectal Cancer

Non-Malignant Causes (False Positive Elevation)  

  • Acute and chronic pancreatitis
  • Hepatocellular jaundice
  • Cirrhosis
  • Acute cholecystitis
  • Cystic Fibrosis

Clinical Application of CA 19-9

  1. Screening – Due to it’s low sensitivity, it has a limited role in screening of pancreatic cancer.
  2. Diagnosis – It may sometimes be normal in cases of pancreatic cancer (false negative) and sometimes be elevated in conditions other than pancreatic cancer (false positive), as listed above. So these factors limit it’s use as a diagnostic test.
  3. Monitoring response to treatment
  4. Detection of early recurrence

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