Diagnostic utility of a p63/α-methyl-CoA-racemase (p504s) cocktail in atypical foci in the prostate

Abstract

Prostatic needle biopsy is the preferred method for diagnosing early prostate cancer, providing specific information. In cases of histological cancer mimics, a diagnosis of atypical small acinar proliferation suspected of but not diagnosed as malignancy can be made. In such cases, and in small focus carcinomas, pathologists use 34bE12, cytokeratin (CK) 5/6 or p63 immunostaining to label basal cells, and a-methylacyl-CoA racemase (AMACR/p504s) immunostaining as a positive prostate cancer marker on two distinct slides. However, in cases of small foci, ambiguous lesions might disappear. The purpose of our study was to improve the sensitivity of a cocktail of two antibodies (p63/p504s) with a sample incubation on 260 prostatic specimens, in order to help make a decision in conjunction with standard histology and CK 5/6 immunostaining. We tested 101 small focus prostatic cancers, 104 atypical small acinar proliferation, 19 high-grade prostatic intraepithelial neoplasia, two atypical adenomatous hyperplasia and 34 benign mimics of cancer. After p63/p504s immunostaining, the final diagnoses retained were as follows: 154 prostatic cancers, 14 atypical small acinar proliferation, 30 high-grade prostatic intraepithelial neoplasia, three atypical adenomatous hyperplasia and 62 benign mimics of cancer. To differentiate malignant from benign lesions, we used the criteria of greater sensitivity to p504s/p63 (95%) than to CK 5/6 (57%) or p63 (86%), and higher specificity for p504s/p63 (95%) than for CK 5/6 (88%) or p63 (81%). With the p504s/p63 cocktail, 89% of the ambiguous lesions were classified vs 53% for CK 5/6. Combined use of the two antibodies, one (p504s) as a positive marker and the other (p63) as a negative marker, with a simple immunostaining procedure, may improve diagnostic performance, sensitivity and specificity, leading to a reduction in the risk of false negatives; this technique in cases of atypical small acinar proliferation should reduce the percentage of residual ambiguous lesions and the need for additional biopsies.

Use of Immunohistochemistry in Routine Workup of Prostate Needle Biopsies: A Tertiary Academic Institution Experience

“…At an estimated cost of $31.00 per immunostain, the average COMMENT The diagnostic utility of HMWK and AMACR have been evaluated extensively in the prostate pathology practice from a diagnostic perspective, but the quality assurance and the cost aspects of the use of IHC in evaluating prostate needle biopsies, a large segment of genitourinary pathology practice, to our knowledge have not been previously addressed. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] It is uncertain, for example, how much IHC is used in routine prostate biopsy practice; what is the appropriate level of IHC use, both from diagnostic and quality assurance purposes; what is the breakdown of the final diagnostic decisions when IHC is used; what are the implications for additional departmental consultations; and what are the associated costs of the use of IHC? Some of these issues, such as the level and the suitability of IHC use in evaluating prostate needle biopsies, are obviously influenced by additional factors, including the type of practice (academic/teaching versus private; general versus specialized; community versus consult), pathologist's level of experience, expertise, and the volume of prostate biopsy material seen, as well as the quality of the produced slides, which may be dependent on the tissue fixation, the thickness of the sections, and the staining quality of the slides.…”

“…The use of IHC for highmolecular-weight keratin (HMWK) and a-methylacyl coenzyme A racemase (AMACR), either individually or in combination, has been studied extensively in prostate pathology practice, primarily as a tool in confirming and establishing cancer diagnosis on prostate needle biopsy and for evaluating challenging and questionable foci in prostate specimens, particularly on needle biopsy. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] In addition, IHC use has risen for the evaluation of prostate needle biopsies because its use in conjunction with morphology is critical to prevent diagnostic errors, especially diagnostic overcalls that may lead to unnecessary radical prostatectomy. Indeed, the use of IHC in prostate biopsy has shown an upward trend over time.…”

Dietary fat’gene interactions in cancer

“…The up-regulation of AMACR in atrophic prostate, PIN, localized and metastatic prostate cancer was further confirmed at the protein level [220,221]. Due to its consistent over-expression in prostate cancer, AMACR is now considered an excellent molecular marker for prostate cancer and has been widely investigated in clinical diagnosis, with both high sensitivity and specificity [220,[225][226][227][228][229].…”

Alpha-methyl CoA racemase expression in renal cell carcinomas

“…The most relevant markers of papillary RCC are vimentin and CK7 [17]. More recently, alphamethyl CoA racemase (AMACR), a peroxymal mitochondrial enzyme involved in the b-oxidation of branched-chain fatty acids and fatty acid derivatives, identified as a molecular marker for prostate cancer [18][19][20][21] on the basis of complementary (cDNA) microarray technology, has also been reported in epithelial tumors [22][23][24] and in kidney cancers [16,25]. Complementary DNA microarray study has demonstrated that AMACR overexpression in papillary RCC is one of the top 10 most highly expressed genes [26,27].…”