Tumor Markers & Cytopathology Objectives: After learning, student should be able to 1. Describe the basic concepts of tumor markers and Asst. Prof. Prasit Suwannalert, Ph.D. (Email: prasit.suw@mahidol.ac.th) Department of Pathobiology Faculty of Science, Mahidol University cytopathology 2. Discuss the applications of tumor markers and cytopathology for cancer diagnosis (SCBM343- Clinical Pathology: 2 nd Semester 2017) 1 2 What are tumor markers?! Tumor markers are substances that are produced by cancer or by other cells of the body in response to cancer or certain benign (noncancerous) conditions.! Most tumor markers are made by normal cells as well as by cancer cells! Tumor markers are produced at much higher levels in cancerous conditions.! These substances can be found in the blood, urine, stool, tumor tissue, or other tissues or bodily fluids of some patients with cancer.! Most tumor markers are proteins. However, more recently, patterns of gene expression and changes to DNA have also begun to be used as tumor markers. 3 4
! Many different tumor markers have been characterized and are in clinical use.! Some are associated with only one type of cancer, whereas others are associated with two or more cancer types.! No universal tumor marker that can detect any type of cancer has been found. 5 How are tumor markers used in cancer care?! Tumor markers are used to help detect, diagnose, and manage some types of cancer.! Although an elevated level of a tumor marker may suggest the presence of cancer, this alone is not enough to diagnose cancer.! Therefore, measurements of tumor markers are usually combined with other tests, such as biopsies, to diagnose cancer. 6! Tumor marker levels may be measured before treatment to help doctors plan the appropriate therapy.! In some types of cancer, the level of a tumor marker reflects the stage of the disease and/or the patient s prognosis (likely outcome or course of disease).! A decrease in the level of a tumor marker or a return to the marker s normal level may indicate that the cancer is responding to treatment, whereas no change or an increase may indicate that the cancer is not responding.! Tumor markers may also be measured after treatment has ended to check for recurrence (the return of cancer). 7 8
Tumor markers and cancer types ALK gene rearrangements and overexpression! Cancer types: Non-small cell lung cancer and anaplastic large cell lymphoma! How used: To help determine treatment and prognosis Alpha-fetoprotein (AFP)! Cancer types: Liver cancer and germ cell tumors! How used: To help diagnose liver cancer and follow response to treatment; to assess stage, prognosis, and response to treatment of germ cell tumors 9 10 Beta-2-microglobulin (B2M)! Cancer types: Multiple myeloma, chronic lymphocytic leukemia, and some lymphomas, urine, or cerebrospinal fluid! How used: To determine prognosis and follow response to treatment Beta-human chorionic gonadotropin (Beta-hCG)! Cancer types: Choriocarcinoma and germ cell tumors! Tissue analyzed: Urine or blood! How used: To assess stage, prognosis, and response to treatment 11 12
BRCA1 and BRCA2 gene mutations! Cancer types: Ovarian cancer! How used: To determine whether treatment with a particular type of targeted therapy is appropriate BCR-ABL fusion gene (Philadelphia chromosome)! Cancer types: Chronic myeloid leukemia, acute lymphoblastic leukemia, and acute myelogenous leukemia and/or bone marrow! How used: To confirm diagnosis, predict response to targeted therapy, and monitor disease status 13 14 BRAF V600 mutations! Cancer types: Cutaneous melanoma and colorectal cancer! How used: To select patients who are most likely to benefit from treatment with certain targeted therapies C-kit/ CD117! Cancer types: Gastrointestinal stromal tumor and mucosal melanoma! How used: To help in diagnosing and determining treatment 15 16
CA15-3/ CA27.29! Cancer type: Breast cancer! How used: To assess whether treatment is working or disease has recurred CA19-9! Cancer types: Pancreatic cancer, gallbladder cancer, bile duct cancer, and gastric cancer! How used: To assess whether treatment is working 17 18 Calcitonin! Cancer type: Medullary thyroid cancer! How used: To aid in diagnosis, check whether treatment is working, and assess recurrence CA-125! Cancer type: Ovarian cancer! How used: To help in diagnosis, assessment of response to treatment, and evaluation of recurrence 19 20
Carcinoembryonic antigen (CEA)! Cancer types: Colorectal cancer and some other cancers! How used: To keep track of how well cancer treatments are working or check if cancer has come back CD20! Cancer type: Non-Hodgkin lymphoma! How used: To determine whether treatment with a targeted therapy is appropriate 21 22 Chromogranin A (CgA)! Cancer type: Neuroendocrine tumors! How used: To help in diagnosis, assessment of treatment response, and evaluation of recurrence Chromosomes 3, 7, 17, and 9p21! Cancer type: Bladder cancer! Tissue analyzed: Urine! How used: To help in monitoring for tumor recurrence 23 24
Circulating tumor cells of epithelial origin! Cancer types: Metastatic breast, prostate, and colorectal cancers! How used: To inform clinical decision making, and to assess prognosis Cytokeratin fragment 21-1! Cancer type: Lung cancer! How used: To help in monitoring for recurrence 25 26 EGFR gene mutation analysis! Cancer type: Non-small cell lung cancer! How used: To help determine treatment and prognosis Estrogen receptor (ER)/ Progesterone receptor (PR)! Cancer type: Breast cancer! How used: To determine whether treatment with hormone therapy and some targeted therapies is appropriate 27 28
Fibrin/ Fibrinogen! Cancer type: Bladder cancer! Tissue analyzed: Urine! How used: To monitor progression and response to treatment HE4! Cancer type: Ovarian cancer! How used: To plan cancer treatment, assess disease progression, and monitor for recurrence 29 30 HER2/ Neu gene ampliflication or protein overexpression! Cancer types: Breast cancer, gastric cancer, and gastroesophageal junction adenocarcinoma! How used: To determine whether treatment with certain targeted therapies is appropriate Immunoglobulins! Cancer types: Multiple myeloma and Waldenstrom macroglobulinemia and urine! How used: To help diagnose disease, assess response to treatment, and look for recurrence 31 32
KRAS gene mutation analysis! Cancer types: Colorectal cancer and non-small cell lung cancer! How used: To determine whether treatment with a particular type of targeted therapy is appropriate Lactate dehydrogenese (LDH)! Cancer types: Germ cell tumors, lymphoma, leukemia, melanoma, and neuroblastoma! How used: To assess stage, prognosis, and response to treatment 33 34 Neuron-specific enolase (NSE)! Cancer types: Small cell lung cancer and neuroblastoma! How used: To help in diagnosis and to assess response to treatment Nuclear matrix protein 22! Cancer type: Bladder cancer! Tissue analyzed: Urine! How used: To monitor response to treatment 35 36
Programmed death ligand 1 (PD-L1)! Cancer type: Non-small cell lung cancer! How used: To determine whether treatment with a particular type of targeted therapy is appropriate Prostate-specific antigen (PSA)! Cancer type: Prostate cancer! How used: To help in diagnosis, assess response to treatment, and look for recurrence 37 38 Thyroglobulin! Cancer type: Thyroid cancer! How used: To evaluate response to treatment and look for recurrence Urokinase plasminogen activator (upa) and plasminogen activator inhibitor (PAI-1)! Cancer type: Breast cancer! How used: To determine aggressiveness of cancer and guide treatment 39 40
5-Protein signature! Cancer type: Ovarian cancer! How used: To pre-operatively assess pelvic mass for suspected ovarian cancer 21-Gene signature! Cancer type: Breast cancer! How used: To evaluate risk of recurrence 41 42 70-Gene signature! Cancer type: Breast cancer! How used: To evaluate risk of recurrence Cytopathology! Cytology is the branch of life science that deals with the study of cells in terms of structure, function and chemistry.! Cytopathology is a branch of pathology that studies and diagnoses diseases on the cellular level. 43! Cytopathology is generally used on samples of free cells or tissue fragments, in contrast to histopathology, which studies whole tissues. 44
Advantage of of cytopathology! Rapid diagnosis with early detection of unsuspected diseases! Confirmation of suspected diseases without surgical trauma! Useful in flow up the course of disease or monitoring therapy Disadvantage of cytopathology! Interpretation of the cellular changes is based only on individual cell observation.! Not always finally diagnosis, so it is confirmed by histopathology in some cases.! Not determine the size and type of lesion of some cases. 45 46 Samples for cytopathologic analysis!! Gynecologic cytopathology! Non-gynecologic cytopathology! PAP test The Papanicolaou test (abbreviated as Pap test, also known as Pap smear, cervical smear, or smear test) is a method of cervical screening used to detect potentially pre-cancerous and cancerous processes in the cervix. " Respiratory cytology! " Breast cytology! " CNS! " Urogenital tract cytology! " Hepato & GI tract cytology! " Other fluids: synovial fluid, corneal! 47 (www.soc.ucsb.edu) 48
(Kross, 1999) 49 50 Superficial cells 1. Ectocervix! 51 52
Parabasal cells Intermediate cells 53 54 55 56 2. Endocervix! 56
References! NIH National Cancer Institute! Bigbee W, Herberman RB. Tumor markers and immunodiagnosis. In: Bast RC Jr., Kufe DW, Pollock RE, et al., editors. Cancer Medicine. 6th ed. Hamilton, Ontario, Canada: BC Decker Inc., 2003.! Prabodh K. Gupta and Zubair W. Baloch. Cytohistology: Essentials and Basic Concepts. 2011! Vinay Kumar, Abul K. Abbas, Jon C. Aster. Robbins Basic Pathology. 9th Edition, 2013. 57 58