Diagnostic Utility of Amacr in Prostatic Carcinoma

Abstract

BACKGROUNDThe aim of the study is to assess the sensitivity and specificity of AMACR (P504S) in the diagnosis of prostatic carcinoma and to correlate serum PSA value in Carcinoma Prostate, atypia, PIN, prostatitis and nodular hyperplasia. This was an observational descriptive study carried out in Department of Pathology, Government Medical College, Kottayam. MATERIALS AND METHODSTotal of 120 cases of prostatic needle biopsies (processed routinely for H and E and IHC) during the period of 18 months from August 2014 to January 2016 were studied. Statistical analysis was done using SPSS version 16. Chi-square test was used to find if there was any statistically significant association between the levels of serum PSA and histopathological findings studied. RESULTSAmong 93/120 cases confirmed as carcinoma by H and E, 85 cases (91.3%) showed AMACR positivity. Among 5/120 cases confirmed as atypical glands suspicious for malignancy by H and E, 4 cases (80%) showed AMACR positivity. Out of 3/120 cases confirmed as PIN by H and E, 2 cases (66%) showed AMACR positivity. Out of 19/120 cases confirmed as benign prostatic hyperplasia by H and E, all the 19 cases (100%) showed AMACR negativity. High grade carcinoma (Gleason pattern 5) showed AMACR negativity. Sensitivity and specificity of AMACR in prostatic carcinoma were 90% and 100% respectively. Positive predictive value of AMACR in prostatic carcinoma was 100% and negative predictive value of AMACR in prostatic carcinoma was 65%; 99% of prostatic carcinoma showed high serum PSA value. CONCLUSIONH and E is the gold standard for diagnosing prostatic neoplasia. AMACR helps in confirming the diagnosis of carcinoma in the cases of atypical glands/suspicious of malignancy. But AMACR negativity does not exclude the possibility of carcinoma. So along with positive marker (AMACR), basal cell marker (negative marker, p63/HMWCK) is useful in diagnosing the morphologically suspicious cases. BACKGROUNDThe most common malignancy of prostate is adenocarcinoma, which accounts for more than 25% of all malignancies in men. 1 In developing countries even though prostatic carcinoma is less common, its incidence and mortality is on the rise. 2 It is a disease gaining importance worldwide. In Indian population, the incidence ranges from 5.39 to 6.58/1 lakh population. 3 Currently, the mainstay of detection of early prostatic carcinoma is by the triad of level of total serum PSA, digital rectal examination and TRUS-guided core needle

Future directions for medicinal chemistry in the field of oligonucleotide therapeutics

“…For some applications in vivo, efforts have been made to reduce the number of PS groups in an oligonucleotide, for example, by substituting selected linkages with stable POgroups [27,67] , with alkyl phosphonates [68] , with phosphoryl guanidine (PN) groups (Fig. 1h) [69,70] or with mesyl phosphoramidite (MsPA) groups (Fig. 1i) [71,72] .…”

“…To date, the properties and applications of fully stereopure PS oligonucleotides have been described in a handful of prominent papers [69,80,[88][89][90] . Critical analysis of the data in these works confirms that a stereodefined PS-backbone shows superior potency and duration of action to its stereorandom counterpart, in vitro and in vivo.…”

“…3c), to yield stereopure amidate linkages [69,91] , thereby reducing the PS content of an oligonucleotide without compromising either metabolic stability or stereopurity. The uncharged stereopure PN modification was incorporated into the wings of gapmer oligonucleotides, as well as splice switching oligonucleotides, that showed superior activity to their PS counterparts in the CNS [69] . The authors suggested that these enhanced effects occurred through improved oligonucleotide delivery.…”