Prostate Acid Phosphatase (PAP)

Overview

Prostate Acid Phosphatase (PAP) is a glycoprotein enzyme synthesized by the epithelial cells of the prostate gland. It is a subtype of total acid phosphatase and is abundantly present in prostate tissue and secretions. PAP functions as a phosphomonoesterase, catalyzing the hydrolysis of phosphate esters at an acidic pH.

Physiologically, PAP has a role in semen liquefaction and fertility. Clinically, it is significant as a biomarker for prostate carcinoma, with levels increasing proportionally as prostate cancer progresses. Although small amounts are normally present in blood, elevated serum PAP levels often suggest underlying pathology.

The enzyme exists in multiple isoenzymes and has additional expression in the bone, liver, spleen, and red blood cells, making careful interpretation necessary. Historically, PAP was widely used before PSA testing became standard but still retains importance in monitoring prostate cancer progression, therapy response, and bone metastases.

Symptoms

PAP abnormalities do not directly cause symptoms but reflect underlying disease processes, especially prostate cancer or related conditions. Common associated symptoms include:

1. Genitourinary Symptoms:
   1. Frequent urination, especially at night
   2. Weak or interrupted urine stream
   3. Painful or difficult urination
   4. Blood in urine or semen
2. Systemic Symptoms:
   1. Unexplained weight loss
   2. Persistent fatigue
   3. Pelvic pain or discomfort
3. Advanced Prostate Cancer Symptoms:
   1. Bone pain (common in metastasis)
   2. Back pain and pathological fractures
   3. Erectile dysfunction or infertility

These symptoms often prompt laboratory testing, including PAP alongside other markers such as PSA (Prostate Specific Antigen).

Causes

Abnormal PAP levels may result from both malignant and non-malignant conditions:

1. Elevated PAP Causes:
   1. Prostate cancer (most significant clinical use)
   2. Bone metastases
   3. Acute renal failure
   4. Breast cancer
   5. Liver cirrhosis and liver tumors
   6. Hepatitis and obstructive jaundice
   7. Gaucher disease
   8. Hemolytic anemia
   9. Hyperparathyroidism
   10. Multiple myeloma
   11. Eclampsia
   12. Medications such as anabolic steroids, androgens, and clofibrate
2. Decreased PAP Causes:
   1. Use of phosphates, alcohol, fluorine, or oxalates

Because PAP is not completely specific to prostate cancer, clinical correlation with history and additional biomarkers (e.g., PSA, PCA3) is essential for accurate interpretation.

Risk Factors

Individuals more likely to show abnormal PAP results include:

1. Men over 50 years: Routine screening is often recommended for early detection of prostate cancer.
2. Patients with Prostate Cancer: PAP levels rise with cancer progression and metastasis.
3. Those with Liver Disorders: Conditions like cirrhosis, tumors, or hepatitis influence PAP levels.
4. Bone-Related Conditions: Metastases or bone marrow disorders can elevate PAP.
5. Women with Certain Conditions: Though less common, elevated PAP may occur in breast cancer or eclampsia.
6. Individuals on Specific Medications: Drugs such as anabolic steroids, androgens, and clofibrate may alter PAP levels.
7. Patients with Benign Prostate Conditions: Up to 40% of benign prostatic hyperplasia (BPH) cases show elevated PAP, complicating diagnosis.

Prevention

While prostate cancer and related diseases cannot always be prevented, early detection and proper test preparation can minimize risks:

1. Testing Guidelines:
   1. Baseline PAP levels should be recorded at the first histopathological diagnosis of prostate cancer.
   2. Used for monitoring therapy response and detecting early metastasis.
   3. Avoid prostatic massage or rectal examination for at least 24 hours before testing, as these can falsely elevate results.
2. Sample Collection and Handling:
   1. Collect 3.0 mL of blood in a plain (red-capped) tube.
   2. Separate serum immediately to reduce contact with RBCs.
   3. Stabilize sample with disodium citrate monohydrate (10 mg/mL) or acetic acid (50 μL of 5 mol/L per mL of serum) to maintain pH at 5.4.
3. Reference Ranges:
   1. Newborns: 10.4–16.4 U/mL
   2. Children: 8.0–12.6 U/mL
   3. Adults and elderly: 0.13–0.3 U/mL (Total Acid Phosphatase)
   4. Prostatic-specific component: 0.0–0.6 U/mL
4. Comprehensive Evaluation:
   1. PAP results should be interpreted alongside family history, clinical findings, imaging, and other laboratory results.
   2. Consider PSA and PCA3 tests for diagnostic accuracy.