IMMUNOLOGY & SEROLOGY (TopnotcherQT) > TUMOR MARKERS > Flashcards
TUMOR MARKERS Flashcards
AFP
Hepatic and testicular cancers
Amylase
Pancreatic cancer
CA-125
Ovarian cancer
CA-15.3
Breast cancer
CA-19.9 (related to Le antigens)
Pancreatic cancer
Calcitonin
Medullary Thyroid cancer
CEA
Colorectal cancer (treatment and recurrance)
CYFRA 21-1
- Head and neck tumors (squamous cell carcinoma)
- Lung cancer
- Detection of stage IV Breast cancer, recurrence, and metastasis
Estrogen receptor
Breast cancer
Nuclear matrix protein (NMP-22)
Bard’s BTA Test
Urinary bladder cancer
PSA
Prostate cancer
HCG
- Nonseminomatous testicular cancer
- Choriocarcinoma
Tumor markers that are used for:
- diagnosis/case finding (1)
- staging/prognosis (2)
- detecting recurrence (3)
- monitoring therapy (4)
AFP
CA-125
PSA
HCG
Tumor markers that are used for:
- monitoring therapy (4) only
CA-15.3 (Breast cancer)
Tumor markers that are used for:
- diagnosis/case finding (1)
- staging/prognosis (2)
- monitoring therapy (4)
CA-19.9 (Pancreatic cancer)
Tumor markers that are used for:
- staging/prognosis (2)
- detecting recurrence (3)
- monitoring therapy (4)
CEA (Colorectal cancer)
Tumor markers that are used for:
- staging/prognosis (2) only
Estrogen receptor (Breast cancer)
How can normal cells become malignant?
a. Overexpression of oncogenes
b. Underexpression of tumor suppressor genes
c. Viral infection
d. All of the above
d. All of the above
Normal cells can become malignant through various mechanisms:
- Overexpression of oncogenes: Genetic mutations or amplifications leading to excessive activity of proteins promoting cell growth and division (e.g., Ras, Myc).
- Underexpression of tumor suppressor genes: Mutations or deletions reducing the function of genes regulating cell growth, DNA repair, and apoptosis (e.g., p53, BRCA1).
- Viral infection: Certain viruses (e.g., HPV, EBV, HBV) can integrate into host DNA, disrupting normal cellular regulation and promoting oncogenesis.
Additional mechanisms:
1. Genetic mutations: Spontaneous or environmentally-induced mutations in critical genes.
2. Epigenetic changes: Alterations in gene expression without DNA sequence changes (e.g., DNA methylation, histone modification).
3. Chromosomal instability: Abnormalities in chromosome structure or number.
4. Immune system evasion: Cancer cells developing strategies to evade immune surveillance.
5. Environmental factors: Exposure to carcinogens (e.g., tobacco, UV radiation).
Which of the following best summarizes the concept of tumor development via immunoediting?
a. Tumor cells produce cytokines that are toxic to T cells
b. tumor cells that can escape the immune system have a growth advantage over tumor cells that are destroyed during immunosurveillance
c. T-cell activity causes an increase in MHC expression on tumor cells that allows them to escape the immune system
d. Secreted tumor-associated antigen saturates T-cell receptors and makes T cells incapable of binding to tumor cells
b. Tumor cells that can escape the immune system have a growth advantage over tumor cells that are destroyed during immunosurveillance
Immunosurveillance and immunoediting:
1. Immunosurveillance: Immune system recognizes and eliminates tumor cells
2. Immunoediting: Tumor cells that evade immune detection acquire a selective advantage, leading to tumor progression
Immunoediting process:
1. Elimination: Immune system removes most tumor cells
2. Equilibrium: Residual tumor cells coexist with immune system
3. Escape: Tumor cells develop immune-evasive strategies, leading to uncontrolled growth
Immune-evasive strategies:
1. Downregulation of tumor antigens or MHC molecules
2. Immunosuppressive cytokines (e.g., TGF-β, IL-10)
3. Checkpoint molecules (e.g., PD-L1)
4. Immunosuppressive cells (e.g., Tregs, myeloid-derived suppressor cells)
Understanding immunoediting helps in:
1. Cancer immunotherapy development
2. Targeting immune checkpoints
3. Enhancing anti-tumor immunity
Incorrect options:
a. Cytokines toxic to T cells are part of immune suppression, not immunoediting.
c. Increased MHC expression enhances immune recognition.
d. Antigen saturation is not a primary immunoediting mechanism.
Which of the following is an example of a tumor-specific antigen?
a. BCR/ABL fusion protein
b. CEA
c. CA 125
d. PSA
a. BCR/ABL fusion protein
BCR/ABL fusion protein
This is a tumor-specific antigen resulting from the chromosomal translocation t(9;22) in chronic myeloid leukemia (CML) and some acute lymphoblastic leukemias (ALL). The BCR/ABL fusion protein is unique to cancer cells.
Other options
1. CEA (Carcinoembryonic Antigen): A tumor-associated antigen, not tumor-specific, found in various cancers (e.g., colorectal, lung).
2. CA 125: A tumor-associated antigen, primarily associated with ovarian cancer.
3. PSA (Prostate-Specific Antigen): A tumor-associated antigen, not tumor-specific, elevated in prostate cancer and benign conditions.
Tumor-specific antigens are unique to cancer cells, whereas tumor-associated antigens are overexpressed or aberrantly expressed in cancer cells but also present in normal cells.
Most tumor markers are not used to screen the general population because they
a. cannot be inexpensively quantified
b. do not rise to high enough levels in the presence of cancer
c. can also be elevated in conditions other than the cancer
d. vary too much between patients belonging to different ethnic populations
c. can also be elevated in conditions other than the cancer
Limitations of tumor markers:
1. Lack of specificity: Elevated in non-cancerous conditions (e.g., inflammation, benign diseases)
2. Low sensitivity: Not detectable in early-stage cancer or all cancer types
3. Variability: Expression levels differ among patients and cancer types
Examples:
1. PSA (Prostate-Specific Antigen): Elevated in benign prostatic hyperplasia (BPH) and prostatitis
2. CA 125: Elevated in endometriosis, ovarian cysts, and pelvic inflammatory disease
3. CEA (Carcinoembryonic Antigen): Elevated in smoking, liver disease, and inflammatory bowel disease
Exceptions:
1. Screening for high-risk populations (e.g., BRCA1/2 for familial breast/ovarian cancer)
2. Monitoring cancer treatment response or recurrence
Ideal tumor marker characteristics:
1. High sensitivity and specificity
2. Early detection
3. Exclusive expression in cancer cells
4. Minimal variability among patients
Both AFP and hCG exhibit serum elevations in
a. pregnancy
b. ovarian germ cell carcinoma
c. nonseminomatous testicular cancer
d. all of the above
d. all of the above
Both AFP (Alpha-Fetoprotein) and hCG (human Chorionic Gonadotropin) can be elevated in:
- Pregnancy: hCG is produced by placental trophoblasts, while AFP is produced by fetal liver and yolk sac.
- Ovarian germ cell carcinoma: Certain subtypes, like yolk sac tumors and choriocarcinomas, produce AFP and/or hCG.
- Nonseminomatous testicular cancer: Specifically, yolk sac tumors and choriocarcinomas produce AFP and/or hCG.
Elevation patterns:
1. AFP: Elevated in yolk sac tumors, hepatocellular carcinoma, and some germ cell tumors.
2. hCG: Elevated in choriocarcinomas, germ cell tumors, and some trophoblastic diseases.
Clinical significance:
1. Tumor markers for diagnosis and monitoring
2. Prognostic value in germ cell tumors
3. Differentiation from other cancer types
Other conditions with elevated AFP/hCG:
1. Hepatocellular carcinoma (AFP)
2. Trophoblastic diseases (hCG)
3. Some pancreatic and gastric cancers (AFP)
Suppose a patient with ovarian cancer had a serum CA 125 level of 50 kU/L at initial diagnosis. After her tumor was surgically removed, her CA 125 level declined to 25 kU/L. She received chemotherapy drug #1; after 1 year, her CA 125 level was 40 kU/L. She was then given chemotherapy drug #2 and her CA 125 level rose to 60 kU/L. These results indicate that
a. surgery was effective in removing the patient’s tumor
b. chemotherapy drug #1 was more effective than chemotherapy drug #2
c. both chemotherapy drug #1 and chemotherapy drug #2 were effective
d. neither chemotherapy drug #1 nor chemotherapy drug #2 were effective
d. neither chemotherapy drug #1 nor chemotherapy drug #2 were effective
The reasoning:
- CA 125 decreased after surgery, indicating effective tumor removal.
- CA 125 increased after chemotherapy drug #1, suggesting disease progression.
- CA 125 further increased after chemotherapy drug #2, confirming a lack of efficacy.
Both chemotherapy drugs failed to control the disease, as evidenced by rising CA 125 levels.
All of the following are recommended for cancer screening in the groups indicated except
a. CA 125/women of reproductive age
b. AFP/subjects at high risk for liver cancer
c. PSA/men over 50 with at least 10 years of life expectancy
d. none of the above
a. CA 125/women of reproductive age
CA 125 is not recommended for routine screening in women of reproductive age due to:
- Low specificity (elevated in benign conditions like endometriosis, and ovarian cysts)
- Low sensitivity (not detectable in early-stage ovarian cancer)
- Potential for unnecessary surgeries and complications
Recommended screenings:
b. AFP (Alpha-Fetoprotein) for high-risk individuals, such as:
* Hepatitis B or C carriers
* Cirrhosis patients
* High-risk ethnic groups (e.g., African, Asian)
c. PSA (Prostate-Specific Antigen) for:
* Men over 50 with at least 10 years of life expectancy
* High-risk men (e.g., family history, African American)
Other recommended cancer screenings:
1. Mammography (breast cancer)
2. Colonoscopy (colorectal cancer)
3. Pap smear/HPV testing (cervical cancer)
4. Low-dose computed tomography (lung cancer) for high-risk individuals
The best use of serum tumor markers is considered to be in
a. screening for cancer
b. initial diagnosis of cancer
c. monitoring patients undergoing cancer treatment
d. determining patient prognosis
c. monitoring patients undergoing cancer treatment
Serum tumor markers are most useful for:
1. Monitoring treatment response
2. Detecting recurrence or progression
3. Assessing disease burden
Ideal characteristics for monitoring:
1. Elevated levels in cancer
2. Correlation with tumor burden
3. Rapid changes in response to treatment
Examples of tumor markers for monitoring:
1. CA 125 (ovarian cancer)
2. PSA (prostate cancer)
3. CEA (colorectal cancer)
4. AFP (hepatocellular carcinoma)
Limitations in other uses:
a. Screening: Low specificity and sensitivity, leading to false positives/negatives.
b. Initial diagnosis: Not definitive, requires confirmation with imaging and biopsy.
d. Prognosis: Markers provide limited prognostic information, other factors are more important.
Additional uses:
1. Staging and restaging
2. Detecting residual disease
3. Evaluating treatment efficacy
In order to use a tumor marker to monitor the course of the disease, which of the following must be true?
a. The laboratory measures the marker with the same method over the entire course of that patient’s treatment.
b. The marker must be released from the tumor or because of the tumor, into a body fluid that can be obtained and tested.
c. The marker’s half-life is such that the marker persists long enough to reflect tumor burden but clears fast enough to identify successful therapy.
d. All of the above.
d. All of the above
To effectively monitor disease course using tumor markers:
a. Consistent laboratory methods: Ensure comparable results over time.
b. Tumor-related release: Marker levels should reflect tumor burden or activity.
c. Optimal half-life: Balance between:
* Persistence: Reflecting tumor burden
* Clearance: Allowing detection of successful therapy
Additional considerations:
1. Marker specificity and sensitivity
2. Established reference ranges and thresholds
3. Correlation with clinical status and imaging findings
4. Regular sampling and testing schedules
Examples of markers meeting these criteria:
1. PSA (prostate cancer)
2. CA 125 (ovarian cancer)
3. CEA (colorectal cancer)
4. AFP (hepatocellular carcinoma)
Importance of consistent laboratory methods:
1. Minimizes variability
2. Ensures accurate trend analysis
3. Facilitates informed clinical decisions
Which of the following markers could be elevated in nonmalignant liver disease?
a. AFP
b. CEA
c. CA 15-3
d. All of the above
d. All of the above
All three markers (AFP, CEA, and CA 15-3) can be elevated in nonmalignant liver disease, although the likelihood and magnitude may vary:
- AFP: Liver regeneration, hepatitis, cirrhosis, and fatty liver disease
- CEA: Mild elevations in liver disease, such as cirrhosis and hepatitis
- CA 15-3: Rarely elevated in liver disease, but may be seen in cirrhosis and liver dysfunction
Elevation patterns:
- AFP: More significant elevations in hepatocellular carcinoma
- CEA: Higher elevations in colorectal, lung, and breast cancers
- CA 15-3: Primarily used for breast cancer monitoring
When interpreting results, consider:
1. Clinical context
2. Liver function tests
3. Imaging studies
4. Other tumor markers (if applicable)
Each of the following markers is correctly paired with a disease in which it can be used for patient monitoring except
a. CEA/choriocarcinoma
b. CA 15-3/breast adenocarcinoma
c. CA 125/ovarian adenocarcinoma
d. CA 19-9/pancreatic adenocarcinoma
a. CEA/choriocarcinoma
Reasoning
CEA (Carcinoembryonic Antigen) is not typically used for monitoring choriocarcinoma. Instead:
- hCG (human Chorionic Gonadotropin) is the preferred marker for choriocarcinoma.
- CEA is commonly used for colorectal cancer monitoring.
The other options are correct:
1. CA 15-3: Breast adenocarcinoma
2. CA 125: Ovarian adenocarcinoma
3. CA 19-9: Pancreatic adenocarcinoma
Which of the following is a marker used in immunohistochemical staining to identify tumors of epithelial origin?
a. Cytokeratins
b. Vimentin
c. CD45
d. CD10
a. Cytokeratins
Cytokeratins are intermediate filament proteins expressed in epithelial cells, making them useful markers for identifying tumors of epithelial origin, such as:
1. Carcinomas (e.g., breast, lung, colon)
2. Epithelioid malignancies (e.g., mesothelioma)
Other options:
b. Vimentin: Expressed in mesenchymal cells, used to identify sarcomas and lymphomas.
c. CD45: A leukocyte marker, used to identify hematopoietic malignancies.
d. CD10: Expressed in various cell types, including lymphoid and myeloid cells, and some epithelial tumors.
Cytokeratins are divided into:
1. Low molecular weight (LMW): Cytokeratins 8, 18, and 19
2. High molecular weight (HMW): Cytokeratins 1, 5, 10, and 14
Common cytokeratin antibodies used in immunohistochemistry:
1. AE1/AE3
2. CAM 5.2
3. CK7
4. CK20
Which of the following assays would you recommend to test for chromosomal rearrangements such as the BCR/ABL translocation seen in CML?
a. PCR
b. FISH
c. Microarray
d. Next generation sequencing
b. FISH (Fluorescence In Situ Hybridization)
FISH advantages:
1. High sensitivity and specificity
2. Rapid results (24-48 hours)
3. Visualizes chromosomal rearrangements
4. Detects variant translocations
Alternative Options:
a. PCR (Polymerase Chain Reaction): Useful for detecting BCR/ABL fusion transcripts, but may not identify variant translocations.
c. Microarray: Primarily used for gene expression profiling, not ideal for detecting chromosomal rearrangements.
d. Next-Generation Sequencing (NGS): Comprehensive genomic analysis, but may not be necessary for targeted BCR/ABL detection.
Additional Considerations
1. Cytogenetic analysis (karyotyping) can also detect chromosomal rearrangements.
2. RT-PCR (Reverse Transcription PCR) can quantify BCR/ABL transcript levels.
3. NGS may be useful for comprehensive genomic profiling in advanced cases.
Clinical guidelines:
1. National Comprehensive Cancer Network (NCCN)
2. American Society of Clinical Oncology (ASCO)
3. College of American Pathologists (CAP)
FISH protocol:
1. Probe selection (BCR and ABL-specific)
2. Sample preparation (bone marrow or blood)
3. Hybridization
4. Fluorescence microscopy analysis
Innate immune responses thought to be involved in defense against tumors include
a. NK cell-mediated apoptosis
b. MHC I-restricted T-cell-mediated destruction
c. ADCC
d. All of the above
a. NK cell-mediated apoptosis
NK cells play a key role in innate immunity against tumors through:
1. Recognition of tumor cells lacking MHC I expression
2. Induction of apoptosis (programmed cell death)
The other options are incorrect because:
b. MHC I-restricted T-cell-mediated destruction is an adaptive immune response.
c. ADCC (Antibody-Dependent Cellular Cytotoxicity) involves both innate and adaptive immunity.
NK cell-mediated apoptosis is a crucial innate mechanism for tumor surveillance and elimination.
A woman with breast cancer is treated with a monoclonal antibody to HER2. This is an example of
a. a cancer vaccine
b. an immunotoxin
c. passive immunotherapy
d. active immunotherapy
c. passive immunotherapy
Explanation:
Monoclonal antibodies (mAbs) targeting HER2 (e.g., Trastuzumab) are an example of passive immunotherapy:
- Pre-made antibodies administered to patient
- Bind to HER2 receptors, inhibiting tumor growth
- Do not stimulate immune response
Contrast with:
a. Cancer vaccine: Stimulates active immune response against tumor antigens (e.g., HPV vaccine)
b. Immunotoxin: Conjugated antibody-toxin complex, delivers toxin to tumor cells
d. Active immunotherapy: Stimulates immune system to produce own antibodies/immune response (e.g., checkpoint inhibitors)
Passive immunotherapy advantages:
1. Rapid action
2. Targeted specificity
3. Reduced side effects
Examples of mAbs in cancer therapy:
1. Trastuzumab (HER2+ breast cancer)
2. Rituximab (CD20+ lymphoma)
3. Cetuximab (EGFR+ colorectal cancer)
