Tumor Marker:- Part 5 – M-band, NMP 22, BTA, Oncogenes

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

M Band of Multiple Myeloma

1. The monoclonal band of immunoglobulin is used as a tumor marker.
2. Myeloma components or M band or monoclonal paraprotein is used to diagnose multiple myeloma.
3. 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 the serum and the urine electrophoresis.
   3. > 90 % of patient 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.
4. Bence-Jones 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:

Protein fractions	Result in %	The result of myeloma patient  g/dL	Normal range g/dL
Albumin	35.2	3.1	3.5 to 5.2
α1 – globulin	3.4	0.3	0.2 to 0.4
α2 – globulin	6.8	0.6	0.4 to 0.8
β – globulin	8.0	0.7	0.5 to 1.1
γ – globulin (M band)	46.6	4.1	0.6 to 1.3

 NMP22 (Nuclear matrix apparatus protein)

1. Other names are Bladder cancer marker or bladder tumor antigen
2. Nuclear matrix proteins made the internal structure of the nucleus.
   1. This bladder tumor antigen is a factor H-related protein that is produced by the bladder tumor.
   2. NMP 22 is a nuclear matrix protein that is deposited in the urine during the apoptosis of bladder cancer cells.
   3. 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.
3. 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 the patient who is at greater risk to develop bladder cancer.
   4. NMP22 may be raised in the tumor involving ureter and renal pelvis.
4. Urine sample:
   1. This protein is unstable in the urine if urine is not stabilized immediately, they can get a false result.
5. Normal source 2:
   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 :
   1. Involvement of the basement membrane in the tumor. OR
   2. Produced by the tumor.OR
   3. Combination of both.
3. BTA test was positive in 40% of the cases on cystoscopy proved bladder tumor.
4. While cytology gives only 17% positivity.
5. BTA is a marker of a bladder tumor.
   1. 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.
6. Normal source 2:
   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 the cancers.
4. There are two types of genes :
   1. Oncogene = these are the cell activation genes. Promote tumor formation.
   2. Suppressor gene = these genes are involved in the recognition and repair of damaged DNA.
5. c-erb B-2 is also called an HER-2/neu gene.

Table of Oncogenes

Oncogene	Type of cancer
N-rs mutation	Acute myeloid leukemia, Neuroblastoma
K-rs mutation	Leukemia, Lymphoma
c-myc transduction	B and T cell Lymphoma, Small cell lung cancer
c-erb B-2 amplification	Breast, Ovarian and GI tract cancers
N-myc amplification	Neuroendocrine tumor
bcl-2	Leukemia, Lymphoma

Suppressor gene

1. This is studied that normal cell contains a gene which suppresses the expression of malignancy.
2. The loss of the chromosome 5 gene leads to an increase in cell growth.
3. Metastasis occurs with the loss of genes.
4. The significance of 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 gene BRCA1 and BRCA2.

Table of Suppressor gene:

Suppressor gene	Tumor
RB gene	Retinoblastoma
p53 gene	Breast, colorectal, lung, renal, bladder, sarcoma
BRCA1	Neurofibromatosis, melanoma, breast
BRCA2	Breast

Table of tumor markers

Test	Marker of tumor
Alpha-fetoprotein	Liver cell carcinoma
Vanillylmandelic acid VMA	Pheochromocytoma and neuroblastoma
beta – HCG	Trophoblastic tumors
Liver alkaline phosphatase	liver metastasis,  seminoma, and ovarian cancers
Bone alkaline phosphatase	Osteogenic sarcoma and bone metastasis

The various enzyme in different tumors:

Enzymes	Organs involved in tumor
Alkaline phosphatase	Liver, bone, and sarcoma
Amylase	Pancreas
Aldolase	Liver
Creatine kinase-BB	Breast, colon, ovary, prostate, and lung
Gamma-glutamyltransferase	Liver
Lactate dehydrogenase	Lymphomas, leukemias, liver and other organs
5 nucleotidase	Liver
Prostatic acid phosphatase	Prostate

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

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