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Tissue polypeptide antigen (TPA) and tissue polypeptide specific antigen (TPS)

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TPA and TPS Overview

Tissue Polypeptide Antigen (TPA) and Tissue Polypeptide Specific Antigen (TPS) are related tumor markers that reflect cell proliferation activity, particularly in epithelial cells. They are fragments of intracellular structural proteins called cytokeratins (specifically cytokeratins 8, 18, and 19), which are released into the circulation during cell division and cell death.

Because increased cell proliferation is a hallmark of cancer, elevated levels of TPA and TPS can be found in the blood of patients with various types of epithelial malignancies. However, they are considered non-organ-specific markers, meaning they can be elevated in many different cancer types and also in certain benign conditions involving increased cell turnover or inflammation.

Tumour markers serve as indispensable tools in the realm of cancer detection and diagnosis, offering valuable insights into disease progression and treatment response.

Tissue Polypeptide Antigen (TPA)

Biology

TPA represents a mixture of fragments derived from cytokeratins 8, 18, and 19. These cytokeratins are part of the intermediate filament network within simple and glandular epithelial cells. TPA is considered a "proliferation antigen" because its levels tend to increase when cells are actively dividing or dying, releasing these fragments. The originally described molecular weight was around 22,000 Da (22 kDa), though it represents a heterogeneous mixture.

Indications

TPA has been investigated primarily for:

  • Monitoring patients diagnosed with various epithelial carcinomas, such as:
    • Bladder carcinoma
    • Breast carcinoma
    • Bronchial (Lung) carcinoma
    • Colorectal carcinoma
    • Cervical carcinoma
  • Assessing treatment response and potentially detecting recurrence in these cancers.

Interpretation

  • Normal Range: Typically cited as < 85 - 120 U/L (Units per liter). Reference ranges are highly method-dependent and should be confirmed with the specific laboratory.
  • Elevated Levels:
    • Observed in a significant proportion of patients with the carcinomas listed above, often correlating with tumor burden or stage.
    • Can also be elevated in various benign conditions involving inflammation or increased cell turnover, including benign lung diseases, liver diseases (hepatitis, cirrhosis), and benign diseases of the urogenital tract.
    • Levels may also rise during pregnancy or with infections.

Due to its lack of specificity, TPA is not used for cancer screening or primary diagnosis.

Tissue Polypeptide Specific Antigen (TPS)

Biology

TPS is considered to be a more specific marker related to TPA. It primarily measures soluble fragments specifically derived from cytokeratin 18. Like TPA, TPS is released during cell division (mitosis) and apoptosis/necrosis, reflecting cell proliferation activity in epithelial tissues and tumors derived from them.

Indications

Similar to TPA, TPS has been mainly investigated for:

  • Monitoring treatment response and disease progression in various epithelial cancers, including bladder, breast, lung (bronchus), ovarian, prostate, and gastrointestinal carcinomas.

Interpretation

  • Normal Range: Often cited similarly to TPA, around < 80 - 120 U/L, but again, highly dependent on the specific assay method.
  • Elevated Levels:
    • Observed in patients with various carcinomas, with levels potentially correlating with tumor activity and proliferation rate.
    • Like TPA, TPS can also be elevated in benign inflammatory conditions and other situations involving increased cell turnover (e.g., infections, liver disease).

TPS vs TPA

TPS was developed with the aim of being more specific for carcinoma cell activity than the broader TPA mixture. It represents specific epitopes primarily on cytokeratin 18 fragments released during the S/G2/M phases of the cell cycle.

However, clinical studies comparing the two have yielded mixed results regarding diagnostic sensitivity for specific cancers. The original text suggests that for bladder and lung cancer, TPS sensitivity might actually be lower than TPA's sensitivity. In practice, neither marker has gained widespread acceptance as a primary tumor marker compared to more established markers for specific cancers (like PSA for prostate, CA 125 for ovarian, CEA/CA 19-9 for GI, etc.). Their main potential value lies in reflecting general tumor proliferation activity.

General Limitations (TPA & TPS)

  • Low Organ Specificity: Elevated levels can occur in many different types of epithelial cancers and numerous benign conditions.
  • Low Sensitivity: Often not elevated in early-stage cancers.
  • Not for Screening/Diagnosis: Unsuitable for general population screening or initial cancer diagnosis.
  • Influence of Benign Conditions: Inflammation, infection, liver disease, kidney disease, and pregnancy can all affect levels.
  • Assay Variability: Significant variability between different commercial kits exists.

Their clinical utility is limited, and they are less commonly used than other more established tumor markers in most settings today.

Testing Procedure

  • Sample Type: Blood serum or plasma.
  • Preparation: No specific patient preparation like fasting is generally required.
  • Collection: Standard venipuncture.
  • Analysis: Measured using specific immunoassays (typically ELISA or similar methods).

References

  1. Plebani, M. (1994). TPA and TPS in tumor diagnosis. *Scandinavian Journal of Clinical and Laboratory Investigation. Supplementum*, 219, 28–35.
  2. Björklund, B. (1980). On the nature and clinical use of tissue polypeptide antigen (TPA). *Tumor Diagnostik*, 1, 9–20. (Historical reference on TPA)
  3. Gion, M., Mione, R., Barioli, P., Pizzolitto, S., & Gatti, C. (1994). Tissue polypeptide specific antigen (TPS) in serum and tissues of patients with breast carcinoma. *British Journal of Cancer*, 69(4), 754–758. https://doi.org/10.1038/bjc.1994.145
  4. Tarle, M. (1993). Serial measurements of tissue polypeptide specific antigen (TPS), CA 15-3 and CEA in the management of breast cancer patients. *Anticancer Research*, 13(5A), 1505–1509.
  5. National Cancer Institute (NCI). (n.d.). Tumor Markers. Retrieved from https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-fact-sheet (General information, though TPA/TPS may not be specifically detailed due to less common use).