objectives: • To know the tumour markers in use • and how to use them clinically. • To know the limitations of tumour markers in clinical situations. • To know the markers used in chemotherapy. Alpha fetoprotein • Fetal albumin • Found in germ cell tumours but also other cancers but especially • Liver cancers. Disorders associated with elevated serum AFP • Hepatoma • 90% • Viral hepatitis • 40% • Chronic active • 33% hepatitis • Cirrhosis • 5-50% • Tyrosinaemia • 100% Carbohydrate/cancer antigen CA 125 • Made by epithelial ovarian carcinoma cells • Ovarian cancer marker in 80% but • Found in other diseases too. • Used for prognosis. CA 19 9 • Gastrointestinal • Pancreatic • Colorectal cancers. CA 24 25, CA 27-29 • Breast cancer markers Placental like alkaline phosphatase PLAP • Breast cancer 20% • Ovarian cancer 20% • Seminomas 50%. Cancer markers: hormones • Insulin from insulinoma • Calcitonin from medullary carcinoma of thyroid • Catecholamines from pheochromocytoma • ADH from bronchogenic carcinoma • ACTH from bronchogenic ca • hCG from choriocarcinoma [May give rise to the paraneoplastic syndrome]. Cancer markers: monoclonal proteins (myeloma, unit 13) • Light chain – kappa or lambda • Heavy chain Also use: • Immunoglobulin typing • ALP for bone breakdown • Creatinine for renal function • Haemoglobin from bone marrow • Calcium from bone. Cancer markers: enzymes • LD – lymphoma, leukaemia (tumour necrosis syndrome) germ cell. • CKBB – neuroendocrine. Obsolete? • ALP – placental type, germ cell type, intestinal type (isoenzyme). Obsolete? • ACP – prostate – now obsolete. • PSA (serine protease) - prostate LD in lymphoma: Cancer markers: cell surface antigens
• T cell CD# (cell surface marker) in
lymphomas, leukaemias • Oestrogen and progesterone receptor in breast cancer. Is Tamoxifen likely to work? Cancer markers: acute phase reaction proteins • Alpha-1-acid glycoproteins (orosomucoid) • Alpha-1-anti trypsin • Ceruloplasmin (copper binding) • Haptoglobin • Fibrinogen • C-reactive protein Faecal occult blood Problems with cancer markers 1 – tumour heterogeneity: • Theory is one clone = one cancer type. • Party line is kill the clone kills the cancer but • Chemotherapy works for a while then fails. • Pathology shows different cell lines sometimes. Cells change as cancer ages. Problem with cancer markers 2- immunological control: • We can handle (by immune processes) a cancer billion cells perhaps. • Immune function in cancer not enhanced. • BCG vaccine may help control cancer. • In immune suppressed patients only some types of cancers are seen Karposi’s sarcoma: Problem 3, metastasis: • Not all cancers spread. • No usable marker for this potential Problem 3. secondary spread of cancer. Laboratory tests: • Liver – AFP, GGT – spread from colorectal, breast, lung, pancreas, stomach, testis, uterus, ovary. • Bone – calcium, ALP – from prostate, breast, lung, stomach, testis, uterus, thyroid. • Brain – csf tests-from breast, lung, testis. • Lung – LD - from colorectal, breast, pancreas, stomach, thyroid, liver, uterus. • Peritoneum AMS– from pancreas.