Tumor Markers & Cytopathology
Asst. Prof. Prasit Suwannalert, Ph.D. (Email: [email protected])
Department of Pathobiology Faculty of Science, Mahidol University
(SCBM343- Clinical Pathology: 2nd Semester 2017)� 1
Objectives: After learning, student should be able to
1. Describe the basic concepts of tumor markers and
cytopathology
2. Discuss the applications of tumor markers and
cytopathology for cancer diagnosis
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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. 3
! 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.
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! 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.
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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.
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! 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).
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! 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).
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ALK gene rearrangements and overexpression ! Cancer types: Non-small cell lung cancer and
anaplastic large cell lymphoma ! Tissue analyzed: Tumor ! How used: To help determine treatment and
prognosis
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Tumor markers and cancer types Alpha-fetoprotein (AFP) ! Cancer types: Liver cancer and germ cell tumors ! Tissue analyzed: Blood ! How used: To help diagnose liver cancer and follow
response to treatment; to assess stage, prognosis, and response to treatment of germ cell tumors
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Beta-2-microglobulin (B2M) ! Cancer types: Multiple myeloma, chronic lymphocytic
leukemia, and some lymphomas ! Tissue analyzed: Blood, urine, or cerebrospinal fluid ! How used: To determine prognosis and follow
response to treatment
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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
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BRCA1 and BRCA2 gene mutations ! Cancer types: Ovarian cancer ! Tissue analyzed: Blood ! How used: To determine whether treatment with a
particular type of targeted therapy is appropriate
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BCR-ABL fusion gene (Philadelphia chromosome) ! Cancer types: Chronic myeloid leukemia, acute
lymphoblastic leukemia, and acute myelogenous leukemia
! Tissue analyzed: Blood and/or bone marrow ! How used: To confirm diagnosis, predict response to
targeted therapy, and monitor disease status
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BRAF V600 mutations ! Cancer types: Cutaneous melanoma and colorectal
cancer ! Tissue analyzed: Tumor ! How used: To select patients who are most likely to
benefit from treatment with certain targeted therapies
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C-kit/ CD117 ! Cancer types: Gastrointestinal stromal tumor and
mucosal melanoma ! Tissue analyzed: Tumor ! How used: To help in diagnosing and determining
treatment
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CA15-3/ CA27.29 ! Cancer type: Breast cancer ! Tissue analyzed: Blood ! How used: To assess whether treatment is working
or disease has recurred
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CA19-9 ! Cancer types: Pancreatic cancer, gallbladder cancer,
bile duct cancer, and gastric cancer ! Tissue analyzed: Blood ! How used: To assess whether treatment is working
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Calcitonin ! Cancer type: Medullary thyroid cancer ! Tissue analyzed: Blood ! How used: To aid in diagnosis, check whether treatment
is working, and assess recurrence
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CA-125 ! Cancer type: Ovarian cancer ! Tissue analyzed: Blood ! How used: To help in diagnosis, assessment of
response to treatment, and evaluation of recurrence
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Carcinoembryonic antigen (CEA) ! Cancer types: Colorectal cancer and some other
cancers ! Tissue analyzed: Blood ! How used: To keep track of how well cancer
treatments are working or check if cancer has come back
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CD20 ! Cancer type: Non-Hodgkin lymphoma ! Tissue analyzed: Blood ! How used: To determine whether treatment with a
targeted therapy is appropriate
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Chromogranin A (CgA) ! Cancer type: Neuroendocrine tumors ! Tissue analyzed: Blood ! How used: To help in diagnosis, assessment of
treatment response, and evaluation of recurrence
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Chromosomes 3, 7, 17, and 9p21 ! Cancer type: Bladder cancer ! Tissue analyzed: Urine ! How used: To help in monitoring for tumor
recurrence
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Circulating tumor cells of epithelial origin ! Cancer types: Metastatic breast, prostate, and
colorectal cancers ! Tissue analyzed: Blood ! How used: To inform clinical decision making, and to
assess prognosis
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Cytokeratin fragment 21-1 ! Cancer type: Lung cancer ! Tissue analyzed: Blood ! How used: To help in monitoring for recurrence
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EGFR gene mutation analysis ! Cancer type: Non-small cell lung cancer ! Tissue analyzed: Tumor ! How used: To help determine treatment and
prognosis
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Estrogen receptor (ER)/ Progesterone receptor (PR) ! Cancer type: Breast cancer ! Tissue analyzed: Tumor ! How used: To determine whether treatment with
hormone therapy and some targeted therapies is appropriate
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Fibrin/ Fibrinogen ! Cancer type: Bladder cancer ! Tissue analyzed: Urine ! How used: To monitor progression and response to
treatment
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HE4 ! Cancer type: Ovarian cancer ! Tissue analyzed: Blood ! How used: To plan cancer treatment, assess
disease progression, and monitor for recurrence
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HER2/ Neu gene ampliflication or protein overexpression ! Cancer types: Breast cancer, gastric cancer, and
gastroesophageal junction adenocarcinoma ! Tissue analyzed: Tumor ! How used: To determine whether treatment with
certain targeted therapies is appropriate
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Immunoglobulins ! Cancer types: Multiple myeloma and Waldenstrom
macroglobulinemia ! Tissue analyzed: Blood and urine ! How used: To help diagnose disease, assess
response to treatment, and look for recurrence
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KRAS gene mutation analysis ! Cancer types: Colorectal cancer and non-small cell
lung cancer ! Tissue analyzed: Tumor ! How used: To determine whether treatment with a
particular type of targeted therapy is appropriate
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Lactate dehydrogenese (LDH) ! Cancer types: Germ cell tumors, lymphoma,
leukemia, melanoma, and neuroblastoma ! Tissue analyzed: Blood ! How used: To assess stage, prognosis, and
response to treatment
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Neuron-specific enolase (NSE) ! Cancer types: Small cell lung cancer and
neuroblastoma ! Tissue analyzed: Blood ! How used: To help in diagnosis and to assess
response to treatment
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Nuclear matrix protein 22 ! Cancer type: Bladder cancer ! Tissue analyzed: Urine ! How used: To monitor response to treatment
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Programmed death ligand 1 (PD-L1) ! Cancer type: Non-small cell lung cancer ! Tissue analyzed: Tumor ! How used: To determine whether treatment with a
particular type of targeted therapy is appropriate
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Prostate-specific antigen (PSA) ! Cancer type: Prostate cancer ! Tissue analyzed: Blood ! How used: To help in diagnosis, assess response to
treatment, and look for recurrence
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Thyroglobulin ! Cancer type: Thyroid cancer ! Tissue analyzed: Blood ! How used: To evaluate response to treatment and
look for recurrence
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Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor (PAI-1) ! Cancer type: Breast cancer ! Tissue analyzed: Tumor ! How used: To determine aggressiveness of cancer and
guide treatment
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5-Protein signature ! Cancer type: Ovarian cancer ! Tissue analyzed: Blood ! How used: To pre-operatively assess pelvic mass for
suspected ovarian cancer
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21-Gene signature ! Cancer type: Breast cancer ! Tissue analyzed: Tumor ! How used: To evaluate risk of recurrence
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70-Gene signature ! Cancer type: Breast cancer ! Tissue analyzed: Tumor ! How used: To evaluate risk of recurrence
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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.
! Cytopathology is generally used on samples of free cells or tissue fragments, in contrast to histopathology, which studies whole tissues.
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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
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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.
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Samples for cytopathologic analysis !! Gynecologic cytopathology
! Non-gynecologic cytopathology!
" CNS!
" Respiratory cytology! " Breast cytology!
" Urogenital tract cytology!
" Hepato & GI tract cytology !
" Other fluids: synovial fluid, corneal !47
PAP test
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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.
(www.soc.ucsb.edu)
(Kross, 1999)
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1. Ectocervix !
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Superficial cells
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Intermediate cells
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Parabasal cells
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2. Endocervix !
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! 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.
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References