Foamy gland and pseudohyperplastic carcinomas are two uncommon variants of prostate cancer and often pose diagnostic challenges on needle biopsies. Alpha-methylacyl-CoA-racemase (AMACR) is a recently discovered tumor marker whose expression is significantly upregulated in prostate cancer. However, the original works only studied ordinary prostate cancer without reference to specific morphologic variants. Therefore, the expression and diagnostic utility of AMACR in specific variants of prostate cancer are unknown. In addition, two different antibodies, one monoclonal and one polyclonal, were used in the previous studies. The goal of this study is to examine the expression pattern and diagnostic utility of AMACR in foamy gland and pseudohyperplastic prostate cancer and to compare the diagnostic utility of the two anti-AMACR antibodies in the same prostate needle biopsy series. Prostate cancer with foamy gland or pseudohyperplastic features was retrieved from the Johns Hopkins Hospital Surgical Pathology file. Thirty needle biopsies harboring prostate cancer with foamy gland features and 17 needle biopsies harboring prostate cancer with pseudohyperplastic features were available for this study. Immunohistochemistry for AMACR was performed with two antibodies, a monoclonal one (P504S) and a polyclonal one (AMACR-p), using previously published protocols. Immunohistochemistry for high molecular weight cytokeratin and p63 was performed to confirm the cancer diagnosis. The AMACR staining intensity was graded as negative, weak, moderate, and strong. Only the staining that was significantly stronger than that of background benign glands was considered positive. A total of 68% and 62% of foamy gland prostate cancer was positive for AMACR with P504S and AMACR-p antibodies, respectively. A total of 77% and 70% of pseudohyperplastic prostate cancer was positive for AMACR with P504S and AMACR-p antibodies, respectively. Staining was often heterogeneous with different staining intensities within the same lesion. The mean percentage of stained glands in positive cases was 74.4% (range 25–100%) with P504S and 78.9% (range 20–100%) with AMACR-p in foamy gland prostate cancer and 91% (range 10–100%) with P504S, and 86.7% (range 10–100%) with AMACR-p in pseudohyperplastic prostate cancer. Seven foci of high-grade prostatic intraepithelial neoplasia present in the study cases were all positive for AMACR. The two antibodies were not statistically different in their sensitivity and specificity. In conclusion, AMACR is potentially a useful diagnostic marker for foamy gland and pseudohyperplastic prostate cancer in the following setting. When the pathologist favors the diagnosis of these variants of cancer on routine stained sections and stains for basal cells are negative, yet still a definitive diagnosis of cancer is difficult because of the cancers' deceptively benign appearance, positive staining for AMACR can provide the additional confidence to establish a definitive malignant diagnosis. The major caveat in the interpretation of positive staining is that high-grade prostatic intraepithelial neoplasia cannot be in the differential diagnosis.
Foamy gland and pseudohyperplastic carcinomas are two uncommon variants of prostate cancer. Foamy gland prostate cancer is characterized by abundant xanthomatous-appearing cytoplasm, minimal to no nuclear enlargement, and rare to absent nucleolar prominence. 9 Pseudohyperplastic variant, however, is composed of malignant glands that simulate benign hyperplastic glands architecturally with large branching glands with papillary infolding. 4,7 The diagnosis of prostate cancer with predominantly foamy gland and pseudohyperplastic features is often difficult on needle biopsy because of their deceptively benign-appearing histology, especially when only a small focus of atypical glands is present. Ancillary tests are often required to demonstrate the lack of basal cells. 7
Alpha-methylacyl-CoA-racemase (AMACR), an enzyme involved in the β-oxidation of branched-chain fatty acids and their derivatives, 2 has recently been identified as a tumor marker for several cancers and their precursor lesions. 17 Although its role in prostatic carcinogenesis is unclear, several recent studies have shown that AMACR expression is significantly upregulated in prostate cancer. 5,8,10,17 By immunohistochemistry, a majority of prostate cancer is positive for AMACR (97–100%), although a high proportion of high-grade prostatic intraepithelial neoplasia (HGPIN) and some atrophic glands and foci of adenosis are also positive for this marker. 16,17 As a result, AMACR has been proposed as a positive prostate cancer marker in conjunction with negative basal cell markers (high molecular weight cytokeratin [HMWCK] and p63) in the workup of difficult prostate needle biopsies. 5,8,10 However, the original works only studied ordinary prostate cancer without reference to specific morphologic variants. 5,8,10 Therefore, the expression and the diagnostic utility of AMACR in specific variants of prostate cancer, including foamy gland and pseudohyperplastic variants, are unknown. In addition, two different antibodies, one monoclonal and one polyclonal, were used in the previous studies. 5,8,10 Although these two antibodies yielded similar results, no studies so far have compared them in the same series of prostate needle biopsies.
From the Departments of Pathology (M.Z., J.I.E.) and Urology (J.I.E.), Johns Hopkins Medical Institutions, Baltimore, Maryland, and the Department of Pathology (Z.J.), University of Massachusetts Medical School, Worcester, Massachusetts, U.S.A.
Address correspondence and reprint requests to Jonathan I. Epstein, MD, Johns Hopkins Hospital, Weinberg Bldg., Rm. 2242, 401 N. Broadway St., Baltimore, MD 21287, U.S.A.