Differential Expression of AMACR, p63 and NKX3.1 in Adenocarcinoma and hyperplasia of Prostate gland

Abstract

Prostate cancer is the fourth most frequently occurring cancer in men worldwide and the second leading cause of cancer associated mortality. The overall incidence of prostate cancer has been increasing worldwide in recent years; approximately 1.3 million new cases are reported in the year 2018. This trend has been rising even in the Asian countries, where the incidence had been previously low. However, the accuracy of data about incidence and mortality as a result of prostate cancer in some Asian countries is limited. The cause of this increasing tendency is multifactorial, dietary and lifestyle modifications being a major reason for this rise in incidence. The timely diagnosis of adenocarcinoma prostate is of prime importance because approximately majority of patients with limited cancer had advanced carcinoma on final radical prostatectomy. Under diagnosis of a small focus of prostatic adenocarcinoma might delay early treatment and cause severe adverse consequences for patients. The diagnosis of prostatic cancer is based on a combination of architectural, cytological and ancillary features. Precise tissue diagnosis can be very challenging due to the presence of either a small focus of cancer or due to the presence of several benign lesions that mimic malignancy. Benign prostatic hyperplasia (BPH) is the most common urological condition among elderly men affecting approximately half of men over 50 years of age. It usually commences as a simple micronodular hyperplasia with a subsequent macroscopic nodular enlargement that may lead to bladder outlet obstruction and the development of lower urinary tract symptoms (LUTS). Although prostate-specific antigen (PSA) has been widely used as a fundamental marker for the diagnosis of prostatic carcinoma, it has been shown to be present in benign tissue as well as in malignant tissue. Therefore, its specificity to prostate cancer is restricted.PSA testing has been widely utilized as a mass screening test along with imaging studies for prostate cancer. Immunohistochemistry (IHC) is an important auxiliary tool for pathologists in routine diagnostic work as well as in basic and clinical research. Accurate diagnosis on needle core biopsy or transurethral resection of prostate (TURP) specimen is of absolute importance because if diagnosed initially for malignancy, patient is benefited as a result of a lesser invasive procedure. In our study, we performed immunohistochemistry on 74 cases (37 cases of benign prostate hyperplasia and 37 cases of adenocarcinoma of prostate gland for expression of three immune markers namely AMACR, p63 and NKX3.1 at a tertiary care hospital in Karachi. AMACR Alpha-Methylacyl- CoA- Racemase (AMACR) plays a vital role in the β-oxidation of branched chain fatty acids and fatty acid derivatives since it catalyzes the conversion of several methyl-branched chain fatty acyl-CoAs to their stereoisomers. Over expression of AMACR prostate cancer and its premalignant lesions aids in the detection of this lesion. p63 is an analogue of tumor suppressor gene, and plays a vital role in the development of p63 is squamous epithelia. p63 and basal cells help in the development and maintenance of the prostate. The characterizing feature of prostate cancer, however, is the depletion of basal cells. NKX3.1 is a prostate specific gene encoding a transcription factor that plays an important role in prostate development and carcinogenesis. It plays an important role in normal prostate development, regulating proliferation of glandular epithelium and in the formation of ducts in prostate gland. Our study revealed a significant corelation of Gleason scoring with AMACR p value=0.001. Statistical analysis of the data also revealed corelation of AMACR, p63 AND NKX3.1 expression in the benign and malignant tissues of the prostate gland. The study therefore, concluded that all the three markers can be used to differentiate between benign and malignant lesions of prostate gland. These markers are also helpful in the determining diagnosis of adenocarcinoma prostate.