Cancer part 2
Unit 4. Tumour markers, 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 • Viral hepatitis • Chronic active hepatitis • Cirrhosis • Tyrosinaemia
• 90% • 40% • 33% • 5-50% • 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 2immunological 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.