Tumor Markers

- there is different classification of tumor markers detected for risk of specific cancer or
detectable because of the cancer being present
1. Tumor Formation
- levels are highly detectable if there is already cancer = malignant
- levels are not detectable if patient is normal or benign
2. Proliferation
- there is cancer that metastasize
- spread throughout the body
3. Differentiation
- specificity and sensitivity are not hat high
- doesn't mean you are positive, you already have the underlying condition
Detected in
- solid tumor
- circulating tumor cells in peripheral blood
- lymph nodes in bone marrow
Maybe detected in body tissues or body fluids
- detect for specific increase or absence of specific enzymes or proteins
- do different methodologies and helpful for differentiation of different type of carcinoma

Ideal Characteristics for Tumor Markers

- they are too good to be true
1. Measured easily
- helpful in early detection of the disease
- for certain types of carcinomas, there are still no specific marker for the detection of
early disease
2. High analytical sensitivity of assay method
- rate of false-negative result should be low
3. High Analytical specificity of assay method
- lower rate of false positive result
- important for individuals that are normal or benign conditions
- if there are tumors already, elevated tumor markers are present
4. Cost-effective
- fast-turnaround time
- should be widely available
- they must be available at a reasonable cost but in reality, it is costly
- immunochromatographic testing, the test kit is expensive
5. Test results contribute to patient care and outcome
- must not only be limited with the screening or the presence of the disease
- it should also be helpful for the monitoring, Post-Op, identify if he condition may recur
6. Useful in differentiation of neoplastic from non-neoplastic disease and show positive
correlation
7. Useful for screening of early cancer or predict early recurrence and have prognostic
value

Uses
1. Screening in general population
- majority of tumor markers being monitored are not that specific for certain type of
carcinoma
- positive result doesn’t mean you have the condition
2. Differential diagnosis of symptomatic patients
3. Clinical staging of cancer
4. Estimating tumor volume
5. Prognostic indicator for disease progression
- test for survival rate
- good or bad prognosis
- low response to chemotherapy or hormonal therapy
6. Evaluating the success of treatment
- others may be undetectable if the organ is renewed
7. Detecting the recurrence
8. Monitoring response to therapy
9. post-operative evaluation
10. Surveillance of recurrence

Classification according to function and biochemical characteristics

1. Enzymes or isoenzymes (ALP, PAP)
a. ALP = alkaline phosphatase
- specificity and sensitivity is not high
- primary or secondary liver cancer, metastatic cancer with bone or liver involvement
- identify the condition of the patient
b. Lactate dehydrogenase (LD) = involved in tumor initiation and metabolism
- increased for patient with dysgerminoma
c. Prostatic acid phosphatase (PAP)
- prostate cancer
d. Prostate specific antigen (PSA)
- for male patients can be detected on low levels from normal serum of patients
- increased or elevations cannot be utilized if the patient really has cancer
> Forms
1. A2-macroglobulin = lacks immunoreactivity
2. A1-antichymotrypsin PSA-ACT = immunologically detectable
3. Free PSA and Total PSA = two most conformed being detected, routinely requested
by the physician
Increase in PSA is common for elderly male patient

2. Hormones (calcitonin, bHCG)

a. Calcitonin
- produced by C cells of thyroid gland to control serum calcium level
b. Human Chorionic Gonadotropin (HCG)
- produced by syncytiotrophoblast of placenta
- beta-HCG = first trimester = elevated
c. Inhibin
- to inhibit the secretion of FSH
- elevated to female patients specifically during their post-menopausal stages
- inhibin levels are elevated
- associated with infertility but do not conclude such
- can have increase concentration if they have granulosa cell tumors

3. Oncofetal antigens (AFP, CEA)

a. AFP = alpha-fetoprotein
- function just like the albumin since it is homologous to albumin
- transportation from the mother to the fetus = transfer of nutrients
- detected in fetus in early stages of life
- elevated: non-seminomatous germ cell tumors, hepatocellular carcinoma,
hepatoblastoma in children, advance adenocarcinoma
Applications
- monitoring of NSGCT in combination with HCG
- independent prognostic marker for NSGCT
b. Carcinoembryonic antigen (CEA)
- present in urothelial adenocarcinomas of the female
- we cannot differentiate endocervical from endometrial adenocarcinoma
- mammary or breast
c. Squamous cell carcinoma antigen
- increased with epidermoid carcinoma
d. Mullerian inhibiting substances
- just like inhibin, it is increased in patients in their postmenopausal women
- not commercially available for clinical use

4. Carbohydrate Markers
A. CA antigens
- high molecular weight mucin like glycoprotein expressed by various type of cancer
cells
a. CA 15-3
- breast carcinoma
b. CA 125
- ovarian, endometrial carcinoma
- pancreas, lung, breast, colorectal and gastrointestinal cancer
c. CA 19-9
- carcinoma of colorectal and pancreas
- seen in hepatobiliary, gastric, hepatocellular, breast cancer

5. Receptor Marker
a. ER positive = estrogen receptors
B. Progesterone receptor = PR+
- both positive means good prognosis
- both have higher rate of response to the hormonal therapy specifically those that are
given to the breast cancer
Common hormonal therapy
- tamoxifen
- aromatase inhibitors

6. Protein Markers
a. B2-macroglobulin
- multiple myeloma, Hodgkin lymphoma, chronic inflammation and viral hepatitis
b. Ferritin
- marker for Hodgkin lymphoma, leukemia, liver, lung and breast cancer
c. Thyroglobulin
d. immunoglobulin

Bladder Cancer
- we could detect BTA and NMP-22 but not solely used for diagnosis for this cancer
- gold standard is cystoscopy and urine cytology
- radiographic imaging may also be used

Breast Cancer
- low specificity as they may be affected by other types of cancer
- no tumor marker that can be utilized for its detection
- after their menstruation, check their breast if tumors are growing
- breast cancer tissues should be tested for ER, PR and HER2 antigen
- methods - immunohistochemistry as staining procedure, in-situ hybridization = 2 types:
fluorescence and chromogenic type, reverse-transcriptase PCR
A. Her 2-receptor overexpression detection
- 0-1+ grading = negative
- 2+-3+ = positive
- Ca 15-3 and CA 27.29, CA 27.29 is much more sensitive and specific

Colorectal Cancer
- neither CEA or CA 19-9 is useful as screening test for colorectal cancer
- elevated CEA level before surgery indicates worse prognosis
- useful for monitoring recurrence and response to treatment

Liver Cancer
- Serum AFP

Lung Cancer
- no tumor marker specific to diagnose lung cancer
- radiographic imaging is still the gold standard
- identify through chest x-ray

Thyroid cancer
- thyroglobulin and thyrocalcitonin

Prostate Cancer
- PSA

Testicular Skin
- elevated level of HCG and AFP
- Seminoma: 10% en have high HCG and not AFP
- non-seminoma: can be HCG, AFP or both
- choriocarcinoma: HCG is always raised and AFP is never elevated

Ovarian Cancer
- CA 125 = effective and assesses response of epithelial ovarian cancer to treatment or
to detect recurrence
- confirmation is to do ultrasound testing
- HCG and AFP = useful for diagnosis and follow-up

Melanoma Skin
- no tumor marker for early detection of melanoma
- TA-90 = look for chance of metastasis and S-100 = serum levels are elevated if
disease is widespread = for progression
- Tyrosinase = check if it spreads through peripheral blood

Lymphoma
A. Burkitt's type lymphoma and Leukemia
a. CD25: most sensitive serum marker for tumor burden
b. CD44: High concentration indicates poor prognosis
c. Lactate Dehydrogenase: normal levels are 100-250 IU/L

Conclusion
- screening: most tumor markers fail
1. low prevalence of malignancy in asymptomatic persons
- may be detected in normal or benign patients
2. Not elevated in patients with small-volume (early) cancer
- early stages, there are still no tumor marker for some cancer
- Diagnosis: most markers have low specificity, only for high-risk groups
- Prognosis: markers correlate with tumor burden
- except estrogen and progesterone receptor = higher levels correlate to high
hormonal response to patient with breast cancer
- Monitor treatment response: most markers level alone cannot be used to define
cancer
- Early detection of recurrence

- monitoring and identification for recurrence