Tumor Markers and Cancer Risk Assessment

Tumor Markers

• CA-125 is a tumor marker that is often raised in ovarian carcinoma (epithelial OC - 80%).
• CA-125 can also be raised during pregnancy, due to fibroids, liver and pancreatic disease, endometriosis, pelvic inflammatory disease, and other malignant diseases (lung, breast, colon carcinoma).
• Human epididymis protein 4 (HE4) is a tumor marker for ovarian carcinoma and can also be overexpressed in endometrial cancer.
• Combined CA-125 and HE4 levels may be used in conjunction with ultrasound scans to aid with screening for ovarian carcinoma in high-risk individuals.
• **These markers are determined both before and after treatment for monitoring. **

Breast Cancer

• CA 15-3 levels can be raised in advanced breast carcinoma along with liver cirrhosis and ovarian cysts.
• Family history of breast cancer (BC) is a significant indicator of increased risk.
• BRCA1 and BRCA2 mutations are associated with a higher risk of breast cancer (BC) and ovarian cancer (OC).
  • BRCA1 mutations are also linked higher risk of colon and prostate cancer.
• BRCA1 mutations account for 5% of BC and OC.
• BRCA2 mutations account for 3% of BC and OC.

Estrogen Receptor (ER) and Progesterone Receptor (PR)

• ER and PR assays are crucial for assessing prognosis in breast cancer.
• ER and PR levels in tissue excised during surgery help determine individualized treatment strategies.

Her2

• Her2 is overexpressed in 25-30% of breast cancers.
• Patients with positive ER and PR responses often benefit from endocrine therapy.

CA-19-9

• CA-19-9 may be elevated in patients with pancreatic or colorectal carcinoma, or obstructive liver disease.
• CA-19-9 levels may also be raised in hepatic, thyroid, pulmonary disease, and diabetes mellitus (DM).

Thyroid Cancers

• Thyroglobulin * is a high-molecular-weight protein produced by the follicular cells of the thyroid. High levels are seen in follicular or papillary carcinoma of the thyroid.
• Thyroglobulin antibodies should be measured to assess the potential for reduced thyroglobulin levels.
• Calcitonin is a hormone secreted by parafollicular C-cells of the thyroid gland.
• Elevated Calcitonin levels are indicative of medullary thyroid carcinoma (MTC).
• Calcitonin levels can be elevated before any clinical evidence of a tumor.
• Hereditary MTC may be screened for with a calcitonin stimulation test.

Other Tumor Markers

• Serum paraprotein and urinary Bence Jones proteins are markers for multiple myeloma.
• Plasma lactate dehydrogenase (LDH) activity may be raised in certain hematological conditions, such as lymphomas.

Prostate Specific Antigen (PSA)

• The PSA index, which represents the percentage of free PSA among total PSA, is suggestive of BPH if above 17%, and prostate carcinoma if below 17%.
• Elevated plasma PSA can indicate carcinoma, even within the reference range.
• Plasma PSA levels above 20 μg/L suggest prostatic carcinoma that has spread beyond the prostate gland.
• PSA assays and digital rectal exams are used within screening programs for prostatic carcinoma in at-risk males.
• There is no universally agreed upon screening protocol for prostatic carcinoma in the general population.
• Prostate biopsy is generally indicated for PSA concentrations above 10 μg/L.

Carcinoembryonic Antigen (CEA)

• CEA is produced by various malignant tumors, especially colorectal carcinomas.
• Serial CEA estimations help monitor the effectiveness of treatment and detect recurrence.
• Plasma concentrations of CEA may be unreliable in determining tumor mass.
• High CEA concentrations often are associated with a poor prognosis.
• **CEA may also be elevated in non-malignant gastrointestinal tract conditions and in smokers, limiting its specificity. **

α-Fetoprotein (AFP)

• AFP synthesis is suppressed as the fetus matures.
• High AFP levels are observed in patients with hepatocellular carcinoma (primary hepatomas and hepatoblastomas) and teratoma.
• Moderately raised AFP levels can be due to non-malignant liver disease.

Human Chorionic Gonadotropin (hCG)

• hCG is mainly produced by the placenta, but also by trophoblastic cells of gonadal and extragonadal germ cell tumors.
• Ectopic secretion of hCG can occur in some bronchial carcinomas.
• hCG estimations are used to screen for choriocarcinoma in women who have experienced a hydatidiform mole.
• High hCG levels can indicate malignancy of the gonads, such as seminomas.
• hCG levels are used to monitor response to treatment and tumor recurrence.

Placental Alkaline Phosphatase (PLAP)

• PLAP and placental-like isoenzyme levels are elevated in seminoma and dysgerminoma.
• In combination with AFP and hCG, PLAP is useful for diagnosing and monitoring extragonadal and gonadal germ cell tumors.
• PLAP levels are also elevated in smokers.
• The concentration may be raised in the plasma of patients with ovarian carcinoma (OC) (80% of epithelial OC).

Other Tumor Markers

• Neuronal-specific enolase (NSE), a marker derived from neurodectal tissue, shows elevated plasma levels in small cell lung carcinoma and neuroblastoma.
• Inhibin, produced by the granulosa cells of the ovary and Sertoli cells of the testis, serves as a plasma tumor marker for ovarian granulosa cell tumors and testicular Sertoli cell tumors.
• Squamous cell carcinoma antigen is a potential plasma tumor marker for squamous cell carcinoma of the cervix.
• Chromogranin A is released from neuroendocrine cells, such as those found in phaeochromocytoma and carcinoid tumors.
• Protein S100B, expressed in brain astrocytes, glial cells, and melanocytes, may contribute to monitoring therapy for malignant melanoma.

Roles of Tumor Markers

• Determine risk (PSA)
• Screen for early cancer (Calcitonin, occult blood)
• Diagnose a type of cancer (hCG, catecholamines)
• Estimate prognosis (CA125)
• Predict response to therapy (CA15-3, CA125, PSA, hCG)
• Monitor for disease recurrence or progression (most widely used function)
• Therapeutic selection (Her2/neu, ER, PR)