Prevalence of Mycobacterium tuberculosis in prostatic tissues of patients suspected with different prostatic lesion specially cancer

Abstract

Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis is a global health problem. According to the World Health Organization (WHO) 9 million people developed TB and 1.5 million died from the disease in 2013. Bangladesh stands 6th among 22 high TB burden countries. Pulmonary tuberculosis is the most common form of the disease; however, 20-25% of cases are extra-pulmonary in nature. Genitourinary tuberculosis accounts for 5-10% of extra-pulmonary cases in developed countries and 15-20% of cases in developing countries. Tuberculosis of the prostate gland is seen in 2.6% of genitourinary system. Studies have shown that approximately 20% of all human cancers in adults result from chronic infection and inflammatory states. Chronic prostate inflammation accelerates initiation of prostate cancer originating from basal cells and accelerates prostate cancer progression. There are reports describing tuberculosis of testis and prostate mimicking testicular cancer and prostatitis caused by M. tuberculosis infection serving as a predisposing factor for prostate cancer. This study aims to investigate whether there is any association between tuberculosis of prostate and development of prostatic lesions especially cancer in a cross section of Bangladeshi population. The study was carried out with 85 prostatic biopsy samples collected by trans-urethral resection of prostate (TURP) from patients and also two known TB positive lymph nodes. In addition to prostatic biopsy, venous blood samples were collected from respective individuals for estimation of prostate specific antigen (PSA) which is an aid for diagnosis of prostatic carcinoma. Histopathological diagnosis of 85 patients revealed nodular hyperplasia with chronic prostatitis (NHCP) in 56%, prostatic intraepithelial neoplasia (PIN) in 30.6%, granulomatous prostatitis (GnP) in 3.5% and cancer in 9.4% patients. The mean age of the cancer patients is 70 years. Most of the cancer patients belong to Dhaka division and smoking habit. None of the 85 biopsy sample revealed the presence of M. tuberculosis when analyzed by Ziehl-Neelsen (Z-N) stain and polymerase chain reaction (PCR). The failure of detection of M. tuberculosis from formalin fixed paraffin embedded tissue by conventional PCR prompted us to use Gene Xpert MTB/RIF which is a real-time hemi nested PCR test that simultaneously identifies M. tuberculosis and detects rifampicin resistance directly from clinical specimens. Two samples from each nodular hyperplasia with chronic prostatitis (NHCP), granulomatous prostatitis (GnP) and prostatic intraepithelial neoplasia (PIN) states, all 8 prostatic adenocarcinoma tissue samples were tested for presence of mycobacterial genomic DNA by the Gene Xpert MTB/RIF real time PCR. All these samples came out negative for mycobacterial DNA. Very importantly, the two positive control samples (lymph node tissues from confirmed TB cases) were positive in the Gene Xpert MTB/RIF assay. The finding of the positive results coming out from paraffin-embedded formalin-fixed lymph node tissue samples having confirmed M. tuberculosis infections validates that the absence of response for M. tuberculosis infection in Gene Xpert analysis from paraffin-embedded formalin-fixed prostatic tissues indicates that the prostate tissue samples used in this study did not harbour M. tuberculosis indicating that infection of prostate glands by M. tuberculosis. These findings indicate that tuberculous prostatitis is rare in a cross section of Bangladeshi population investigated in this study. This finding highlights the need of performing sensitive molecular test such as Gene Xpert in formalin fixed paraffin embedded tissue in ruling out whether a suspected patient is infected with M. tuberculosis or not.