1. Doç.Dr. Jale Çoban Klinik Biyokimya Uzmanı
Tumor markers
Doç.Dr. Jale Çoban
Klinik Biyokimya Uzmanı

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

3. Classification Onkofetal proteins Carbohydrate antigen Enzymes
Carcinoembryonic antigen (CEA)
Alpha-fetoprotein (AFP)
Human chorionic gonadotropin (hCG)
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

4. Hormones and hormone receptors
ACTH and other endocrine hormones
Brest estrogen and progesterone receptors
Proteins as tumor markers
Β2- 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

5. 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

6. 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

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

8. COMMON TUMOR MARKERS CEA - Monitor colorectal, breast, lung cancer
CA Ovarian cancer monitoring
CA 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 Monitor recurrences of bladder cancer

9. 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

10. 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.

11. 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

12. 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

13. 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.

14. Cirrhosis (AFP)

15. Hepatocellular carcinoma

16. Germ cell tumors (Testis Tm)

17. CEA (carcinoembryonic antigen)
Described by Gold and Freedman in1965 as a marker for Colorectal Cancer
Glycoprotein with a carbohydrate composition ranging from % 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

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

19. Increased levels of CEA
Colorectal carcinoma
Pancreatic carcinoma
Lung carcinoma
Breast carcinoma

20. CEA Distribution In Patients With Malignant Disease
% Distribution of CEA
0-3
ng/ml
3.1 – 10
>10
Colorectal 28 20 52
Breast 50 27 23
Ovarian 80 16 4
Pulmonary 39 29 32

21. colorectal carcinomas

22. colorectal carcinomas (CEA)

23. HCG (HumanChorionic 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

24. Germ cell tumors (Testis Tm)

25. 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 CA125)

26. Pancreatic Cancer

27. Pancreatic Cancer

28. Pancreatic Cancer

29. Pancreatic Cancer

30. Pancreatic Cancer

31. 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 CA19-9, for pancreatic cancer.

32. 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 22
Cervical 66 15
Colorectal 76 11 12

33. Over Ca

34. Pancreas Ca

35. Over Ca

36. Over Ca

37. Over Ca

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

40. Breast Cancer

41. Breast Cancer

43. Breast Cancer

44. Breast Cancer

45. Breast Cancer

46. Metastatik meme Ca

48. 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.

49. 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

50. Prostate cancer

51. Prostate cancer

52. ?

54. METASTATİK KOLON CA

55. NÜKS OVER CA

56. ?

57. OVER CA

58. METASTATİK MEME KANSERİ

59. ?

60. ?

61. 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)