Tumor Markers

• Tumor markers in the diagnosis and monitoring of tumors are some more examples.

M-Band of Multiple Myeloma

1. The monoclonal band of immunoglobulin is used as a tumor marker.

Myeloma components:

1. M-band or monoclonal paraprotein is used to diagnose multiple myeloma.
2. Myeloma protein is an abnormal immunoglobulin fragment, such as an immunoglobulin light chain, that is produced in excess by an abnormal monoclonal proliferation of plasma cells, typically in multiple myeloma.
   1.  Other terms used are M-protein, M-component, M-spike, or paraprotein.
   2. This M-protein is found in serum and urine electrophoresis.
   3. > 90 % of patients will Multiple myelomas shows M-band in electrophoresis.
      1. The M band (protein) is paraprotein visible on electrophoresis. Giving a tall peak on a densitometer, also called M-spike.

Bence-Jones proteinuria:

1. It is protein is a light chain excreted in the urine of Multiple myeloma cases.
   1. Decreasing the level of Bence-Jones protein in the treatment shows a good response to treatment.

5. M-band in the myeloma patients on electrophoresis, when total protein is 8.8 g/dL:

 NMP 22 (Nuclear matrix apparatus protein 22)

1. Other names are Bladder cancer marker or bladder tumor antigen.
2. Definition of NMP 22:
   1. NMP 22  detects a nuclear protein, called NuMA (Nuclear mitotic apparatus), that is released from the nuclei of the tumor cells when they die.
3. Mechanism of NMP 22:
   1. Nuclear matrix proteins make the internal structure of the nucleus.
   2. This bladder tumor antigen is a factor H-related protein that is produced by the bladder tumor.
   3. NMP 22 is a nuclear matrix protein that is deposited in the urine during the apoptosis of bladder cancer cells.
   4. Their role is the regulation of DNA replication and synthesis of RNA.
4. This protein is excreted in the urine.
   1. Normally none or very little amount of this protein is found in the urine.
5. This is recommended for the follow-up of Transitional cell carcinoma of the urinary tract.
   1. This is a cheaper marker for the recurrence of bladder cancer.
   2. This is elevated in bladder cancer.
   3. NMP22 is a good screening test for a patient who is at greater risk of developing bladder cancer.
   4. NMP22 may be raised in the tumor involving the ureter and renal pelvis.
6. NMP 22 interpretations:
   1. NMP 22 is advised in patients who have urinary blaader cancer.
   2. It is quite sensitive but nonspecific.
   3. When NMP 22 performed after 1 to 6 weeks of the urinary bladder tumor surgery, is raised indicates recurrence of the tumor.
   4. NMP 22 results are normal in 80% of the patients with no disease.
   5. Infection may give false positive results due to the inflammatory cells (WBCs). Basically WBCs are the source of the false positive result.

Urine sample:

1. This protein is unstable in the urine. If urine is not stabilized immediately, they can get a false result.

Normal NMP22:

1. 1. <10 units/mL.

Bladder tumor-associated Antigen (BTA)

1. BTA are high molecular weight polypeptides.
2. BTA presence in the urine may be due to the following:
   1. Involvement of the basement membrane in the tumor. OR
   2. Produced by the tumor. OR
   3. Combination of both.
3. BTA represents 70% sensitivity and 70% specificity.
4. BTA test was positive in 40% of the cases on cystoscopy, proving bladder tumor.
5. While cytology gives only 17% positivity.
6. BTA is a marker of a bladder tumor.
7. But BTA is not a good screening test because this may be raised in other conditions like:
   1. Recent urologic surgery.
   2. Calculi.
   3. Urinary tract infection.

Normal source 2:

1. 1. <14 units/mL

Genetic markers

1. This is considered that multiple genetic alterations may lead to uncontrolled proliferation of the cells and result in cancers.
2. This gene abnormality also gives rise to metastases.
3. Evaluation of chromosomal changes may help to diagnose cancers.
   1. c-erb B-2 is also called an HER-2/neu gene.

Indications for genetic testing:

1. It is advised for the diagnosis of carrier identification like sickle cell trait, and Tay-Sach disease.
2. It advised for prenatal diagnosis of abnormal;it like Down’s syndroem.
3. It is advised for screening of newborns for comgenital hypothyroidism, and PKU.

There are two types of genes:

Oncogene :

• These are the cell activation genes. Promote tumor formation.

Suppressor gene:

•  These genes are involved in recognizing and repairing damaged DNA.

Table of Oncogenes

Suppressor gene

1. This is studied that normal cell contains a gene that suppresses the expression of malignancy.
2. The loss of the chromosome 5 gene leads to increased cell growth.
3. Metastasis occurs with the loss of genes.
4. The significance of the detection of mutation in the tumor suppressor gene help in the diagnosis and prognosis of the tumor.
5. This mutation of the suppressor gene also helps to predict susceptibility when the mutation is carried in the germline e.g., breast cancer genes BRCA1 and BRCA2.

Table of Suppressor gene:

Table of tumor markers

The various enzyme in different tumors:

Questions and answers:

• Please see in Tumor marker parts 1, 2,  and 3.