Some of the cancer mutations include the ff.: 1. (Activation/Deactivation) of oncogenes 2. Growth factor (regulation/dysregulation) 3. Loss of the tumor (enhancer/suppressor) gene 4. Mutation of the cell cycle and (DNA/RNA) repair genes 5. (Activation/Deactivation) of adhesion molecules 6. (Dormancy/Stimulation) of angiogenesis genes 7. (Downregulation/Upregulation) of proteases

1. Activation 2. Dysregulation 3. Suppressor 4. DNA 5. Activation 6. Stimulation 7. Upregulation

Which among the factors does NOT determine cancer severity? 1. Tumor size 2. Histology 3. Regional lymph node involvement 4. Toxin secreted 5. Metastasis 6. Histologic assessment

4. Toxin secreted Note: Severity is determined by combining the factors above

(P) Lec 2: Tumor Markers (Part 1) Flashcards by Kchianna Lauren Coronel

Cancer is a general term to describe how many types of malignancies can affect how many tissue types?

Note: 2 numerical answers

200 malignancies for 50 tissue types

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Cancer is referred to as uncontrolled cell growth which is also known as what?

Tumorigenesis (of cells)

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Cancer may develop into a solid mass (tumor) and be spread to other areas of the body during what process?

Metastasis

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TOF: Cancer is considered as the leading cause of mortality in underdeveloped countries

False (DEVELOPED)

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TOF: Cancer is mainly caused by genetic mutations

True

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Most cases of cancer nowadays are caused by what kind of mutations?

Acquired genetic

Note: Mutations may be acquired or genetic/inherited but cancer nowadays is described as “acquired genetic”

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Some of the cancer mutations include the ff.:

(Activation/Deactivation) of oncogenes
Growth factor (regulation/dysregulation)
Loss of the tumor (enhancer/suppressor) gene
Mutation of the cell cycle and (DNA/RNA) repair genes
(Activation/Deactivation) of adhesion molecules
(Dormancy/Stimulation) of angiogenesis genes
(Downregulation/Upregulation) of proteases

Activation
Dysregulation
Suppressor
DNA
Activation
Stimulation
Upregulation

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TOF: Mutations that may cause tumorigenesis are NOT THE SAME with the mutations that may cause metastasis

True (cannot be both at the same time)

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Which among the factors does NOT determine cancer severity?

Tumor size
Histology
Regional lymph node involvement
Toxin secreted
Metastasis
Histologic assessment

Toxin secreted

Note: Severity is determined by combining the factors above

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In cases of solid tumors, they may be classified into what which correlates with the severity of the disease?

4 stages

Note: An increasing stage means that the disease is spreading (systemic)

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Cancer stages are presented as a function of what in terms of regionality and to other surrounding tissues?

Function of invasion and spread

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Cancer Staging Progression

The tumor is localized in the organ or tissue that it mainly affects

Stage I

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Cancer Staging Progression

There is an invasion of the primary tumor through the epithelium and into the BVs
Once inside the BVs, it is assumed that it is now circulating within the blood

Stage II

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Cancer Staging Progression

There is migration of the tumor cells into the regional lymph nodes

Stage III

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Cancer Staging Progression

Stage III is also known as?

Lymph node involvement stage

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Cancer Staging Progression

Involves the metastasis and invasion of tumor cells into distant tissue

Stage IV

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These are either produced directly by the tumor or as an effect of the tumor on healthy tissues

Tumor Markers

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What Makes an Ideal Tumor Marker?

Refers to the quality of only being produced by the specific organ that is affected by the tumor

Tumor-specific

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What Makes an Ideal Tumor Marker?

Refers to the quality of being easily distinguishable between an affected and unaffected individual

Absent in healthy individuals

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What Makes an Ideal Tumor Marker?

Refers to the quality of being detected as early as possible

Elevated at an early stage

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What Makes an Ideal Tumor Marker?

Refers to the quality of being detected in any specimen

Readily detectable in body fluids

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TOF: As of now, there is still no ideal tumor marker that fits all the criteria

True

Note: Markers can be used alongside signs and symptoms as well as histology in order to produce a diagnosis

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What happens to normal cells when they proliferate and/or dedifferentiate?

They become cancer cells

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Give the specific tumor marker

These (2) reflect increased cellular proliferation

HER2 and Prostate-specific Antigen (PSA)

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# Give the specific tumor marker This represents the dedifferentiation process of cancer

Carcinoembryonic Antigen (CEA)

# Give the specific tumor marker These (2) focus on collective changes in malignant cells

Genomics and Proteomics

# Types of Tumor Markers Includes Beta-2 Microglobulin and Immunoglobulins which are used for therapy purposes

Serum Proteins

# Serum Protein Markers This is a non-specific tumor marker present on the surface of all nucleated cells which makes the specific cell indistinguishable

Beta-2 Microglobulin

# Serum Protein Markers These are mostly used for hematologic malignancies

Immunoglobulins

# Types of Tumor Markers - The first class of tumor markers to be discovered - Includes the carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP)

Oncofetal Antigens

# Types of Tumor Markers These are specific markers of secreting tumors

Hormones

# Types of Tumor Markers These are specific markers of secreting tumors which are commonly found in urine

Metabolites

# Types of Tumor Markers - These are useful in classifying tumors in therapy - Includes Estrogen Receptor/Progesterone Receptor (ERPR)

Receptors

# Receptor Markers This receptor is known to be a serologic marker which immediately warrants a specific therapy once a solid tumor malignancy is found

Estrogen Receptor/Progesterone Receptor (ERPR)

# Types of Tumor Markers - Comes from the metabolic demands of high-proliferative cells - Also used to monitor the success of a therapy - Are usually seen in serum specimens

Enzymes

# Identify the Enzyme Tumor Marker - Tumor type: Prostate cancer - Method: Immunoassay - Specimen: Serum - Clinical utility: Prostate CA screening, therapy, monitoring, and recurrence

Prostate-specific Antigen (PSA)

# Identify the Enzyme Tumor Marker - Tumor type: Hematologic malignancy - Method: Enzyme assay - Specimen: Serum - Clinical utility: Prognostic indicator; elevated nonspecifically in numerous cancers

Lactate Dehydrogenase (LD)

# Identify the Enzyme Tumor Marker - Tumor type: Metastatic carcinoma of bone, hepatocellular carcinoma, osteosarcoma, lymphoma, and leukemia - Method: Enzyme assay - Specimen: Serum - Clinical utility: Determination of liver and bone involvement; nonspecific elevation in many bone-related and liver cancers

Alkaline Phosphatase (ALP)

# Identify the Enzyme Tumor Marker - Tumor type: Neuroendocrine tumors - Method: Radioimmunoassay and Immunohistochemistry - Specimen: Serum - Clinical utility: Prognostic indicator and monitoring disease progression for neuroendocrine tumors

Neuron-specific Enolase

# Identify the Serum Protein Tumor Marker - Tumor type: Plasma cell dyscrasia - Method: Serum protein electrophoresis or Immunofixation electrophoresis - Specimen: Serum - Clinical utility: Diagnosis and therapeutic monitoring of plasma cell malignancies

Serum M-protein

# Identify the Serum Protein Tumor Marker - Tumor type: Plasma cell dyscrasia - Method: Immunoassay - Specimen: Serum - Clinical utility: Diagnosis and therapeutic monitoring of plasma cell malignancies

Serum Free Light Chains

# Identify the Serum Protein Tumor Marker - Tumor type: Hematologic malignancies - Method: Immunoassay - Specimen: Serum - Clinical utility: Prognostic marker for lymphoproliferative disorders

Beta-2 Microglobulin

# Identify the Endocrine Tumor Marker - Tumor type: Neuroblastoma, pheochromocytoma, and paraganglionoma - Method: HPLC - Specimen: 24H urine - Clinical utility: Diagnosis of neuroblastoma

Homovanillic Acid (HVA) and Vanillylmandelic Acid (VMA)

# Identify the Endocrine Tumor Marker - Tumor type: Neuroblastoma, pheochromocytoma, and paraganglionoma - Method: HPLC - Specimen: 24H urine - Clinical utility: Screening and diagnosis of pheochromocytoma

Metanephrines (fractionated)

# Identify the Endocrine Tumor Marker - Tumor type: Neuroblastoma, pheochromocytoma, and paraganglionoma - Method: HPLC and LC-MS/MS - Specimen: 24H urine - Clinical utility: Screening and diagnosis of pheochromocytoma, paraganglionoma, and neuroblastoma

Catecholamines (fractionated)

# Identify the Endocrine Tumor Marker - Tumor type: Carcinoid tumors - Method: HPLC - Specimen: 24H urine - Clinical utility: Diagnosis of carcinoid tumors

Hydroxyindoleacetic acid (5-HIAA)

# Identify the Endocrine Tumor Marker - Tumor type: Carcinoid tumors - Method: HPLC - Specimen: Serum - Clinical utility: Diagnosis of carcinoid tumors

Serotonin

# Identify the Endocrine Tumor Marker - Tumor type: Medullary thyroid cancer (MTC) and neuroendocrine tumors - Method: Immunoassay - Specimen: Serum - Clinical utility: Screening response to therapy and monitoring for the recurrence of MTC

Calcitonin

# Identify the Endocrine Tumor Marker - Tumor type: Parathyroid adenoma - Method: Immunoassay - Specimen: Serum - Clinical utility: Diagnosis and postsurgical monitoring of primary hyperparathyroidism

Parathyroid hormone (PTH)

# Identify the Endocrine Tumor Marker - Tumor type: Pituitary adenoma, ectopic growth hormone-secreting tumor - Method: Immunoassay - Specimen: Serum - Clinical utility: Diagnosis and post-monitoring of acromegaly

Growth Hormone (GH)

# Identify the Endocrine Tumor Marker - Tumor type: Pituitary adenoma - Method: Immunoassay - Specimen: Serum - Clinical utility: Diagnosis and post-surgical monitoring of prolactinoma

Prolactin (PRL)

# Identify the Endocrine Tumor Marker - Tumor type: Pituitary adenoma and ectopic adrenocorticotropic hormone-producing tumor - Method: Immunoassay - Specimen: Serum - Clinical utility: Diagnosis of an ectopic adrenocorticotropic hormone-producing tumor

Adrenocorticotropic Hormone (ACTH)

# Identify the Endocrine Tumor Marker - Tumor type: Adrenal tumors - Method: Immunoassay - Specimen: Serum or urine - Clinical utility: Diagnosis of Cushing's syndrome and adrenal adenoma

Cortisol

# Identify the Endocrine Tumor Marker - Tumor type: Posterior pituitary tumors - Method: Immunoassay - Specimen: Serum - Clinical utility: Diagnosis of syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Antidiuretic Hormone (ADH)

# Identify the Endocrine Tumor Marker - Tumor type: Pheochromocytoma, neuroblastoma, carcinoid tumors, and small cell lung cancer - Method: ELISA or RIA - Specimen: Serum - Clinical utility: Diagnosis of carcinoid tumors, pheochromocytomas, and neuroblastomas

Chromogranin A

# Identify the Endocrine Tumor Marker - Tumor type: Insulin-secreting tumors - Method: ELISA or Immunoassay - Specimen: Serum - Clinical utility: Diagnosis of insulinoma

C-peptide

# Identify the Endocrine Tumor Marker This detects the presence of Zollinger-Ellison Syndrome

Gastrin

Endocrine tumor markers include what 2 types of tumor markers?

Hormones and Metabolites

In endocrine tumor markers, are the ff. hormones or metabolites? HVA, VMA, catecholamines, metanephrines, and 5-HIAA

Metabolites

In endocrine tumor markers, the rest of the markers are hormones except for this by-product of insulin production

C-peptide

Metabolites require what specimen for testing and what method? Note: 2 answers

Specimen: 24H urine Method: HPLC

This is a disease due to an excess in the production of the growth hormone

Acromegaly

# Identify the Carbohydrate and CA Antigen Tumor Marker - Tumor type: GI cancer and adenocarcinoma - Method: Immunoassay - Specimen: Serum - Clinical utility: Monitoring of pancreatic cancer

CA 19-9

# Identify the Carbohydrate and CA Antigen Tumor Marker - Tumor type: Metastatic breast cancer - Method: Immunoassay - Specimen: Serum - Clinical utility: Response to therapy and detecting recurrence

CA 15-3

# Identify the Carbohydrate and CA Antigen Tumor Marker - Tumor type: Metastatic breast carcinoma - Method: Immunoassay - Specimen: Serum - Clinical utility: Response to therapy and detecting recurrence

CA 27-29

# Identify the Carbohydrate and CA Antigen Tumor Marker - Tumor type: Ovarian cancer - Method: Immunoassay - Specimen: Serum - Clinical utility: For monitoring therapy

CA-125

# Identify the Receptor Tumor Marker - Tumor type: Breast cancer - Method: IHC - Specimen: Biopsy - Clinical utility: Hormonal therapy indicator

Estrogen Receptor and Progesterone Receptor (ER/PR)

# Identify the Receptor Tumor Marker - Tumor type: Breast, ovarian, and GI tumors - Method: IHC, FISH, and ELISA - Specimen: Biopsy - Clinical utility: Prognostic and hormonal therapy indicator

Her-2/neu

# Identify the Receptor Tumor Marker - Tumor type: Head, neck, ovarian, and cervical cancers - Method: IHC - Specimen: Biopsy - Clinical utility: Prognostic indicator

Epidermal growth factor receptor

# Receptor Tumor Markers This is the specimen of choice since these markers are present in the cells which make up the tissues

Biopsy

# Oncofetal Antigens Alpha fetoprotein (AFP) is commonly measured together with this to determine the type of cancer, whether it is seminomatous or non-seminomatous testicular cancer

hCG

# Is it seminomatous or non-seminomatous? Embryonal cancer, teratoma, choriocarcinoma, and yolk sac tumor

Non-seminomatous

# Is it seminomatous or non-seminomatous? Seminoma

Seminomatous (it is the ONLY one)

# Identify the Oncofetal Antigen Marker AFP: Increased hCG: Not increased

Yolk sac tumor

# Identify the Oncofetal Antigen Marker AFP: Not increased hCG: Increased

Choriocarcinoma

# Identify the Oncofetal Antigen Marker AFP: Increased hCG: (+/-)

Embryonal CA

# Identify the Oncofetal Antigen Marker AFP: Not increased hCG: Not increased

Teratoma

# Identify the Oncofetal Antigen Marker AFP: Not elevated in pure tumors hCG: (+/-)

Seminoma

# Uses/Applications of Tumor Markers - Uses PSA and AFP - A biopsy indicator involving histotechniques

Screening

# Uses/Applications of Tumor Markers - Uses metanephrines, HVA/VMA, prolactin, PTH, chromogranin A, cortisol, and ACTH - High levels are indicative of a disease

Diagnosis

# Uses/Applications of Tumor Markers - Uses B2-microglobulin, CA-125, CEA, LDH, Her-2/neu, ER, and PR - Receptor status is used as an indication of chemotherapy

Prognosis

# Uses/Applications of Tumor Markers TOF: Tumor marker concentration increases with tumor progression, the higher the stage of the tumor, the higher chance of metastasis

True

# Uses/Applications of Tumor Markers - Uses CA-125, CA 19-9, CEA, AFP, hCG, PSA, and SPE - Observes the efficacy of chemotherapy or residual diseases post-surgery

Monitoring treatment

# Uses/Applications of Tumor Markers TOF: Tumor markers are only useful in determining a prognosis

False (can also determine whether a specific therapy is effective or not)

# Uses/Applications of Tumor Markers TOF: Markers are only measured before a patient has undergone therapy

False (after as well)

# Uses/Applications of Tumor Markers Initially, there is a/an (increased/decreased) tumor marker at diagnosis

Increased

# Uses/Applications of Tumor Markers - Uses CA-15-3, CA-125, CEA, AFP, hCG, and PSA - There is an increased association with relapse

Detection of recurrence

The possibility of cancer recurrence is taken into account when a patient experiences the same set of what that they have already experienced before?

Symptoms

# Lab Considerations for Tumor Marker Measurement There is a wide range of ________ in tumor markers by orders of magnitude

Concentrations (hence why tumor markers are difficult to measure in different samples)

# Lab Considerations for Tumor Marker Measurement There is ________ of the tumor marker concentration between different manufacturers due to a lack of harmonization and standardization

Variability

# Methods of Detection - The most commonly used method to measure tumor markers - Markers are detected using capture and label antibodies

Immunoassays

# Methods of Detection When analyte concentrations exceed the analytical range excessively, both capture and label antibodies are saturated leading to a lack of sandwich formation (decreased signal), what is this event called?

Hook Effect

# Methods of Detection - This refers to the shape of the concentration-signal curve when reagents are saturated with excess antigen - Can result in falsely low measurements

Hook Effect

# Methods of Detection This is done to prevent the hook effect from happening

Dilution techniques

# Methods of Detection A disadvantage of the Immunoassay technique wherein there are excessively high levels of markers that can result in excess antigen

Hook Effect

# Methods of Detection A disadvantage of the Immunoassay technique wherein the presence of heterophile antibodies (e.g. human anti-animal antibodies [HAAA] and human anti-mouse antibodies [HAMAs]) can result in false positives and negatives

Interference

# Methods of Detection TOF: The immunoassay technque is not affected by icteric, lipemic, and hemolyzed samples and antibody cross reactivity

False (is affected)

# Methods of Detection Lipemic samples will only be accepted using the Immunoassay technique if the patient is sufffering from what 2 conditions?

1. Hyperlipoproteinemia 2. Liver damage

# Methods of Detection - Used to detect small molecules (e.g. endocrine metabolites) and catecholamines in plasma and urine

HPLC

# Methods of Detection In HPLC, catecholamines and their metabolites are used for the diagnosis of what 3 conditions?

1. Neuroblastoma (epinephrine, norepinephrine, and dopamine) 2. Pheochromocytoma (metanephrines) 3. Carcinoid tumors (5-HIAA)

# Methods of Detection TOF: HPLC does not produce any linearity/hook effect

True

# Methods of Detection - Used for the detection of tumor markers directly within solid tissues - Similar to immunoassays but a specific cell type is determined - e.g. ERPR is used for breast cancer detection

Immunohistocytochemistry

# Methods of Detection - These are released from cells when necrosed or have underwent changes in permeability - However, this cannot be used to identify a specific tumor or site of tumor

Enzyme Detection

# Commonly Requested Tumor Markers - A major fetal serum protein and major carcinoembryonic protein - Elevated in primary hepatocellular carcinoma (HCC) and germ cell tumors, specifically testicular cancer - Also elevated in pregnancy and benign liver diseases

Alpha Fetoprotein (AFP)

# Commonly Requested Tumor Markers TOF: Low levels of AFP in hepatocellular carcinoma = poor progonisis

False (high levels)

# Commonly Requested Tumor Markers - A mucin protein - Detects ovarian tumors at an early stage - The only clinically accepted serologic marker for ovarian cancer - Also elevated in endometriosis (myoma), 1st trimester of pregnancy, and during menstruation

Cancer Antigen 125 (CA-125)

# Commonly Requested Tumor Markers Aside from CA-125, this can also be used for ovarian CA diagnosis as it is less frequently increased in non-malignant conditions (e.g. endometriosis)

Human Epididymis Protein (HE4) Note: An increased CA-125 and HE4 is very evident for ovarian CA

# Commonly Requested Tumor Markers - The most widely used marker for colorectal cancer - Also elevated in lung, breast, and GI tumors and in impaired clearance - Associated with cell adhesions - Is NOT USED FOR SCREENING as it is sometimes regarded as non-specific for colon cancer

Carcinoembryonic Antigen (CEA)

# Commonly Requested Tumor Markers TOF: All instances of increased CEA levels point to cancer

False (it can also be increased when clearance is impaired)

# Commonly Requested Tumor Markers - A hormone normally secreted by trophoblasts of the placenta to maintain the corpus luteum during pregnancy - Is elevated in trophoblastic tumors, choriocarcinoma, ovarian, and testicular tumors (psammomatous or non-psammomatous) - Used for the detection of gestational trophoblastic diseases or hydatidiform moles

Human Chorionic Gondatotropin (hCG)

# Commonly Requested Tumor Markers This type of hCG is sensitive and specific for aggresive neoplasms

Beta-hCG (not alpha or total hCG)

# Commonly Requested Tumor Markers Beta-hCG has 2 subunits which are?

Intact and Free

# Commonly Requested Tumor Markers - Are serine proteases that regulate the viscosity of the seminal fluid - It aids in dissolving the cervical mucus cap to allow the penetration of sperm - Is measured via immunoassay to detect prostate cancer, infection, irritation, and benign prostatic hyperplasia

Prostate-specific Antigen (PSA)

# Commonly Requested Tumor Markers This form of PSA is present in the serum

Free form

# Commonly Requested Tumor Markers This form of PSA is bound to alpha 1-antichymotrypsin and alpha 2-macroglobulin

Complexed form

# Commonly Requested Tumor Markers TOF: When measuring PSA via immunoassays, it is able to detect those that are bound to alpha 2-macroglobulin

False (alpha 1-antichymotrypsin) Note: PSA complexed with A2-macroglobulin is not detectable

# Commonly Requested Tumor Markers A (high/low) level of the free form of PSA correlates with malignancy

Low

# Commonly Requested Tumor Markers Screening for prostate cancer is ideally done at what age?

> 50 years old

# Commonly Requested Tumor Markers What level of PSA is considered normal?

< 4 ng/mL

# Commonly Requested Tumor Markers TOF: AFP can only be detected in pregnancy and tumors related to the reproductive system

False (can also be found in liver diseases)