Tumor markers Do Dr Jale oban Klinik Biyokimya

Tumor markers Doç. Dr. Jale Çoban Klinik Biyokimya Uzmanı

Definition • Tumor markers are substances produced either directly by tumor cells or by a tumorcell-induced synthesis in non-tumorous cells.

Classification • Onkofetal proteins • Carcinoembryonic antigen (CEA) • Alpha-fetoprotein (AFP) • Human chorionic gonadotropin (h. CG) • Carbohydrate antigen • • CA-125 CA-19 -9 CA-15 -3 and CA 27 -29 CA- 72 -4 • Enzymes • • • Creatin kinasa Lactat dehidrogenasa Prostata acid phosphatase Prostate specific antigen (PSA) Neuron-specific enolasa (NSE) Amylase

• Hormones and hormone receptors • ACTH and other endocrine hormones • Brest estrogen and progesterone receptors • Proteins as tumor markers • • Β 2 - microglobulin C-peptid Ferittin Tireoglobulin • Other markers – Cytokeratin-19 (CYFRA 21 -1) • Tissue polypeptide-antigen (TPA) • Tissue polypeptide-specific (TPS) antigen • Squamous cell carcinoma (SCC) antigen

IDEAL TUMOR MARKER • Be specific to the tumor • Level should change in response to tumor size • An abnormal level should be obtained in the presence of micrometastases • The level should not have large fluctuations that are independent of changes in tumor size • Levels in healthy individuals are at much lower concentrations than those found in cancer patients • Predict recurrences before they are clinically detectable • Test should be cost effective

• Criteria for ideal tumor marker, which would have sensitivity and specificity 100% have not been fulfilled by any known tumor marker • Use can be helpful to diagnose the cancer but it can not to be the only criteria

İndication • Early detection of malignant tumors in high -risk groups • Use in primary diagnosis • Prognostic utility • Therapy monitoring • Early detection on tumor recurrence

COMMON TUMOR MARKERS • • • CEA - Monitor colorectal, breast, lung cancer CA-125 - Ovarian cancer monitoring CA 15 -3 - Monitor recurrences of breast cancer AFP - Germ cell tumors, liver cancer Total PSA - Screen and monitor prostate cancer Free PSA - Distinguish prostate cancer from BPH HCG - Germ cell and trophoblastic tumors Hormone receptors - Breast cancer therapy NMP 22 - Monitor recurrences of bladder cancer

Tumor markers are not suited for screening asymptomatic individuals because they have a too low organ and tumor specificity as well as a too low predictive value positive of a test

AFP (alpha – fetoprotein) • The most widely used biochemical blood test for liver cancer - hepatocellular carcinoma (HCC) is alpha-fetoprotein (AFP) • AFP is a protein normally made by the immature liver cells in the fetus.

AFP (alpha – fetoprotein) • Malignant Conditions 1. Liver cancer - hepatocellular carcinoma 2. Germ cell tumors (cancer of the testes and ovaries) 3. Metastatic cancer in the liver (originating in other organs) • Non-Malignant Conditions Pregnancy Cirrhosis Hepatitis

Absolute indication • Suspected hepatocellular carcinoma • Germ cell tumors (testes, ovaries, extragonadal tumors) • Follow-up of patients after treatment for germ cell tumors or primary liver cell cancers or of those still undergoing treatment, e. g. Postoperatively or during/after irradiation and chemotherapy

Relative indications • Monitoring patients liver cirrhosis for the development of primary liver cell cancer • Monitoring patients who are at increased risk for germ cell tumors , e. g. cryptorchidism and healthy monozygotic twin siblings of patients with a testicular tumor. • Monitoring patients following resection of a testicular tumor who are in complete remission, because of the increased risk of developing a second, contralateral tumor.

Cirrhosis (AFP)

Hepatocellular carcinoma

Germ cell tumors (Testis Tm)

CEA (carcinoembryonic antigen) • Described by Gold and Freedman in 1965 as a marker for Colorectal Cancer • Glycoprotein with a carbohydrate composition ranging from 50 - 85% of molecular mass • It is normally produced during fetal development, but the production of CEA stops before birth. • CEA levels are raised in heavy smokers

CEA (carcinoembryonic antigen) • CEA levels 5 - 10 times upper limit of normal suggests colon cancer • Differential diagnosis of liver tumors • CEA is not used to screen for colon cancer

Increased levels of CEA • • Colorectal carcinoma Pancreatic carcinoma Lung carcinoma Breast carcinoma

CEA Distribution In Patients With Malignant Disease % Distribution of CEA Colorectal 0 -3 ng/ml 28 3. 1 – 10 ng/ml 20 >10 ng/ml 52 Breast 50 27 23 Ovarian 80 16 4 Pulmonary 39 29 32

colorectal carcinomas

colorectal carcinomas (CEA)

HCG (Human. Chorionic Gonadotropin) • Absolute indications 1. Germ cell tumors (cancer of the testes and ovaries) – hydatiform mole and choriocarcinoma in women , testicular cacer in men 2. Extragonadal germ tumors

Germ cell tumors (Testis Tm)

CA 19 -9 Suspected presence of • pancreatic, • hepatobiliary (liver cancer, biliary cancer), or • gastric cancer • Diagnosis and monitoring of colorectal cancer( second-line tumor marker after CEA) and ovarian cancer (second-line tumor marker after CA 125)

Pancreatic Cancer

CA 125 • CA-125 glycoprotein molecular weight 200 -1, 000 kda • Introduced in 1983 by Bast for ovarian cancer • Cut-off: 35 U/ml • The major diagnostic relevance of CA 125 is in assisting the diagnosis of ovarian cancer, evaluating the success of treatment, and the disease course. • Furthermore, it may be used as a second-line marker, after CA 19 -9, for pancreatic cancer.

CA-125 Distribution In Patients With Malignant Disease % Distribution of CA-125 Cancers <35 U/ml 35 -65 U/ml >65 U/ml Ovarian 14 9 77 Lung 56 19 25 Breast 82 8 10 Endometrial 70 8 22 Cervical 66 15 19 Colorectal 76 11 12

Over Ca

Pancreas Ca

Over Ca

CA 15 -3 • CA 15 -3 is a useful parameter for monitoring the disease course of patients with metastatic breast cancer.

Breast Cancer

Breast Cancer

Metastatik meme Ca

NSE (neuron specific enolase) • NSE is useful for monitoring the outcome of treatment and disease course in patients with neuroendocrine tumors, in particular small cell lung cancer and neuroblastoma.

PSA (prostate-spesific antigen) • Screening of asymptomatic men > 50 years of age for the presence of prostate cancer, together with digital rectal examination and transrectal ultrasound examination/biopsy on the individual findings

Prostate cancer

METASTATİK KOLON CA

NÜKS OVER CA

OVER CA

METASTATİK MEME KANSERİ

PSA Prostate-specific antigen • PSA is a protein produced by the cells of the prostate gland. • PSA is present in small quantities in the serum of normal men, and is often elevated in the presence of prostate cancer and in other prostate disorders prostatitis (inflammation of the prostate) and benign prostatic hyperplasia (BPH)