TUMOUR MARKERS

01. INTRODUCTION

This is an emerging field in medicine. Many researches are going on this topic. Tumour markers are important in diagnosing; treating and predicting the outcome of patients with different tumours.

02. DEFINITION

Tumour Marker is a substance present in the tumour or produced by the tumour or produced by the host in response to a tumour and it could be used to determine the presence of a tumour by measuring its concentrations in the blood or in other body fluids.
An ideal tumour marker should be produced only by the tumour cells and should be detectable in body fluids and it should not be present in normal individual an in benign conditions. But in reality this type of tumour markers are not available.

03. TYPE OF TUMOUR MARKERS

I. Enzyme or Isoenzyme
II. Hormones
III. Oncofoetal antigens
IV. Carbohydrate antigens
V. Receptors
VI. Abnormal genetic products
VII. Abnormal genes

I. Enzymes

Enzymes and isoenzymes are not specific enough to identify the type of cancer and the organ involved, except prostate specific antigen.
Ø Prostate specific antigen (PSA) is a glycoprotein expressed only by normal prostate tissue, benign hyperplastic and cancerous prostatic tissue. It has a mild protease activity. Increased level of PSA alone is not sufficient for diagnosis because it is also increased in benign prostatic hyperplasia as well. Therefore, combination of digital rectal examination and high levels of PSA followed transrectal ultrasonography should be done.
Ø Prostatic acid phosphatase is an enzyme which hydrolyses phosphate esters in acid PH. This is primarily produced by the prostate but is also present in red cells, liver, spleen and kidney. Therefore it is not specific.

II. hormones

A carcinoma may secrete hormones that are usually secreted by the tissue of origin (calcitonin by medullary carcinoma of the thyroid gland, hCG by choriocarcinoma). Some carcinoma may secrete unexpected hormones and they are known as ectopic hormones production in paraneoplastic syndrome (ACTH in small cell carcinoma of the lung, ADH in small carcinoma of the lung).

III. Oncofoetal antigens

Foetal antigens are proteins produced during the foetal life but disappear or present in very low level after birth. But malignant transformation of cells can cause reactivation of certain genes and produce Oncofoetal proteins (alpha fetoprotein, carcinoembryonic antigen).
Ø Alpha fetoprotein (AFP) is a glycoprotein and it is a marker of Hepatocellular carcinoma and germ cell carcinomas. The normal blood level is less than 10 microgram/ liter. The benign condition like hepatitis and cirrhosis can also result in high level of AFP (< 200microgram/l).If the level is higher than 1000microgram/l, it will be highly suggestive of carcinomas. Maternal AFP level can also be used as an indicator of foetal neural tube defect.
Ø Carcinoembryonic antigen (CEA) is a glycoprotein and it is a tumour marker of colorectal carcinoma (70%), lung carcinoma (45%), breast carcinoma (40%), gastric carcinoma (50%) and pancreatic carcinoma (55%).The normal blood level is less than 3 microgram/l. This tumour marker is used as a treatment monitoring tool in above mentioned carcinomas.


IV. Carbohydrate markers

Carbohydrate related tumour markers are either present on the tumour cell surface or secreted by the tumour cells. These are more specific than enzymes and hormones. Common carbohydrate tumour markers are CA 153 ( a marker of breast carcinoma) and CA 125 ( a marker of ovarian and endometrial carcinoma.

V. Receptors

Oestrogen and progesterone receptors are used in breast carcinoma as indicators for hormonal therapy. Patients who are positive for these receptors respond to hormonal therapy, and therefore, are associated with a better prognosis.

VI. Genetic markers

Genetic markers are used in;
Ø As an aid to diagnosis ( BRCA1 and BRCA2 genes in breast carcinoma)
Ø As a prognostic indicator (HER/Neu gene and P53 gene are poor prognostic indicators of breast carcinoma)



04. CLINICAL USES OF TUMOUR MARKERS

i) As an aid in diagnosis
Since most tumour markers are not specific enough, carcinomas are not usually diagnosed on elevated tumour marker value alone. But this can be used as an adjuvant in diagnosis.


ii) In monitoring of treatment
This the area in which most tumour markers are widely used (AFP in treatment of testicular germ cell tumour)


iii) Follow up of a treated patient
Even after successful treatment, patients should be followed up for evidence of recurrence (thyroglobulin in the follow of patients with follicular carcinoma of the thyroid).

iv) Clinical staging of the tumour
Some tumour markers correlate well with the total tumour mass. By quantification of such tumour markers it is possible to predict the tumour burden and tumour progression at the time of diagnosis (hCG in choriocarcinoma and AFP in testicular teratoma).

v) As a screening method
Since most tumour markers are not specific and sensitive enough, they are not recommended for the screening purpose, except in high risk population. In medullary carcinoma of thyroid (in MEN syndrome) screening of close relatives is done by measuring calcitonin level.