TUMOUR MARKERS

Tumour markers are substances that present in the body in concentration which is related to the presence of a tumour. Sensitivity measures elevated tumour marker level in the presence of particular tumour. Specificity measures proportion of patients without tumour with normal marker levels, i.e. true negative. Positive predictive value is the percentage of positive results of tumour marker which are true positive.

The ideal tumour marker should have 100% sensitivity and 100% specificity. Tumour markers are used in screening, diagnosis, as prognostic indicator, to monitor therapy, and for early diagnosis of relapse. Tumour markers may have a high sensitivity in patients with advanced cancer but most have a low sensitivity in patients with early stage cancer.

Diagnostic sensitivity is the conditional probability that a person having a disease will be correctly identified by a clinical test, i.e., the number of true positive results divided by the number of true positive and false negative results. Diagnostic specificity is the conditional probability that a person not having the disease will be correctly identified by a clinical test, i.e., the number of true negative results divided by the number of true negative and false positive results.

Predictive value is the conditional probability that a clinical test result correctly identifies a patient as having or not having a disease, i.e., the predictive value of a positive test (positive predictive value) is the probability that a person with a positive test is a true positive (i.e., does have the disease) and the predictive value of a negative test (negative predictive value) is the probability that a person with a negative test does not have the disease. The predictive value of a screening test is determined by the sensitivity and specificity of the test, and by the prevalence of the condition for which the test is used.

Biomarker may assist in delineating reactive/inflammatory atypia from premalignant dysplasia and may serve to target early chemoprevention strategies before irreversible genetic alterations associated with carcinogenesis. Biomarker evaluation is an emerging field of the basic and clinical sciences which promises to add a new dimension to the conventional clinical and pathological evaluation of cancer. A major goal of biomarkers is to predict patients who will develop or who already have metastatic disease before initiating radical cystectomy. Biomarkers may be cell-associated or may exist as soluble markers in a variety of body fluids or serum. Cellular biomarkers are of special interest to the pathologist because localisation within the cell of origin assists in defining pathological processes and allow qualitative or quantitative biomarker assessment.

The urine sample reflects the entire urinary tract. Cancer develops through an overlapping network of molecular changes.

There are 3 types of genetic changes in cancer cells: 1- inactivation of normal gene expression by gene deletion and/or mutation; 2- alteration of gene products that maintain genomic stability; 3- upregulation of normal gene expression by mutation or amplification.

The success of the screening is determined by outcome measurements showing: 1) a shift toward less advanced clinical and pathological stages in detected cancers; 2) prolonged survival time after diagnosis; and 3) decreased disease-specific mortality in the screened population in comparison with an unscreened population. Screening tests are evaluated in terms of sensitivity, specificity, and predictive value. Sensitivity is the ability of a test to designate people with a disease as positive.

The purpose of screening, therefore is to detect high-grade cancers when they are still in a premuscle-invading stage when they can be readily managed by endoscopic and intravesical means.

Dysplasia refers to several types of abnormal cell configuration that range between normal to carcinoma in situ (CIS). Hyperplasia refers to an increase in the number of cells present without any premalignant abnormalities.

Biomarkers may be cell-associated or may exist as soluble markers in a variety of body fluids or serum. Cellular biomarkers are of special interest to the pathologist because localisation within the cell of origin assists in defining pathological processes and allow qualitative or quantitative biomarker assessment.

Criteria for biomarkers: 1- Biomarkers should fit expected biological mechanisms. 2- Biomarker assay should have acceptable sensitivity, specificity, positive predictive value and accuracy. 3- Biomarker assay should be relatively easy and cost-effective. 4- Biomarkers should have a clinical utility, functional role, contribution to biomarker profile, and adaptability to automation.

Early markers are expressed in the tumour, adjacent field, and histologically normal urothelium, whereas later markers are expressed in tumour. Biomarkers antedate conventional cytology by at least 1 year in disease detection.

Articles by R.A.S Hemat

Clinical Orthomolecularism Classroom