One of the most commonly diagnosed cancers in Australia for males is Prostatic Adenocarcinoma (PA) or commonly known as Prostate cancer. The 25 years old detection method of PA is called prostate specific antigen (PSA) and has increasing issues of overdiagnosis and overtreatment for patients as it only has a sensitivity of 83.4% per 1.1ng/mL. To improve screening methods, immunohistochemistry (IHC) of prostatic tissue has increased detection methods to diagnose PA. IHC uses antibodies to bind to specific antigens (proteins) on a histological tissue sample. IHC is used for clinical diagnosis of abnormal tissue such as increased cell proliferation, programmed cell death (apoptosis) and death of diseased cells (necrosis). IHC uses various markers that can determine if the PA is prostate specific or basal cell associated. An example of a basal cell associated IHC test is the detection of cytokeratin 34βE12. This marker utilizes high molecular weight present in prostatic basal cells and diagnose benign and malignant proliferation. Cytokeratin 34βE12 stains basal cells specifically in the prostatic gland and a loss of basal cells is an indication of PA. The Progensa PCA3 Assay uses the PCA3 as a biomarker in IHC for prostate cancer detection. This assay is aimed at men over 50 years of age that have had more than one negative biopsy as a true marker of this negative result. The assay uses a prepared in vitro amplification test that measures the concentration of PCA3 and PSA messenger RNA (mRNA) with a patient’s urine and calculates a score. Low PCA3 scores can be diagnostically assumed as low volume and low-grade disease. Increased scoring of the PCA3 level indicates a high probability of cancer and a higher grade of cancer. This assay has correlated controversially with other methods of testing tumor aggressiveness, grade and volume.
Men scoring a low PCA3 that, have previously been diagnosed with prostate cancer, are recommended a long-term treatment of 5α-reductase inhibitors. Although the Progensa PCA3 Assay is relativity new it has already highlighted treatment options with more research being conducted into tailored treatment for patients with specific PA. A commonly used antibody in prostatic IHC is AMACR (2-methylacyl-CoA) or commonly known as P504S. The frequently used antibody P504S, is localized in cytoplasmic and granular staining and is over expressed in prostate cancer. Is a relatively specific marker for prostate malignant tumors and is found in majority of PA and ductal carcinomas. A pitfall of P5045 is that it may be nonreactive in hyperplastic (increase in cell size) prostatic tissue. In comparison to P504S and PSA, P5045S an overall better antibody that is more highly specific. PSA is a secretory protein that contains a single chain glycoprotein of serine protease. It is used more commonly as a serum cancer marker but can also be used in IHC as a prostate specific marker of normal and malignant tissue. Some limitations with PSA include its use as a specific immunomarker is that poorly differentiated and metastatic carcinomas may lose expression and antigen/antibody binding may not occur correctly. The clear pitfall of the immunomarker PSA is that it can be reactive in non-prostatic tissue such as breast.
A Case study of a 63-year-old man with metastatic PA highlights the advancing use of new IHC biomarkers and the eventual phasing out of PSA. The patient was presented in hospital with his left lymph node enlarged and a family history of gastric cancer. A serum PSA was completed with high results and a biopsy of the prostate was administered. The biopsy showed a poorly to moderately differentiated adenocarcinoma however, when an IHC PSA stain was conducted the results were negative. This is a rare yet odd result and further IHC was conducted with P504S. The results from the P504S show a positive result of PA however, the less specific IHC PSA was negative in the poorly differentiated stain. From the positive P504S result the patients started an appropriate treatment of an androgen blockade and 8 months later showed a decline in serum PSA level.
In conclusion, as the PA had already metastasized the IHC PSA was not sensitive enough to correctly show the correct results and may have further impacted the tailored treatment for the patient.