Tumor Markers & Cytopathology

Asst. Prof. Prasit Suwannalert, Ph.D. (Email: prasit.suw@mahidol.ac.th)

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