TUMOUR MARKERS

A 56-year old woman with a history of alcohol abuse and liver cirrhosis attended A&E with acute abdominal pains. A panel of tumour markers were requested with results as follows:AFP = 5 kU/L (<7)CA125 = 48 kU/L (<35)CA199 = <10 kU/L (<33)CEA = 3 μg/L (<5)

(a) Name two possible causes of elevated CA125 in this lady.
Ans: Ovarian cancer, cirrhosis, ascites, pancreatitis, inflammation of GI tract, peritonitis

(b) The biomarkers listed above are proteins produced by the tumour cell. State another class of molecule that is currently used as a tumour biomarker giving one example plus the malignancy it is most associated with.

Ans: Hormones: e.g ACTH; pituitary, Calcitonin; medullary thyroid cancer Enzymes eg LDH; germ cell, NSE; lung Neurotransmitters: eg noradrenaline; pheochromocytoma  dopamine; neuroblastoma.

 (c) Give two reasons why tumour markers should not be used in isolation to diagnose malignancy.
Ans: Inadequate sensitivity; low result cannot exclude malignancy.

Inadequate specificity; may be elevated in benign conditions.

(d) Give two general examples of when the measurement of tumour markers is clinically useful.
Ans: Monitoring response to therapy.
Detection of recurrence after treatment or period of remission.

(e) List three properties of the ideal cancer biomarker.

Ans: Detectable only when tumour is present. Sensitive enough to detect small treatable tumours. Specific for type and site of malignancy Correlate with tumour burden.

(f) Using hCG as an example, briefly discuss the analytical problems associated with tumour marker assays.

Ans: Include following up to maximum of four: Assay standardization  Heterogeneous molecule (intact, core fragment, nicked, hyperglycosylation); different manufactures use antibodies with differing specificities.

Biological variation: Different tumours produce different forms of hCG; international reference preparation may not represent biological specimen.

FRCPath: Part 1. Examination in Clinical Biochemistry Specimen Short Answer Question