title: Utility of α-methylacyl-coenzyme-A racemase (p504s) immunohistochemistry in distinguishing endometrial clear cell carcinomas from serous and endometrioid carcinomas.
abstract: The expression of α-methylacyl-coenzyme-A racemase (AMACR) has previously been reported in 75% to 100% of urethral/bladder clear cell carcinomas, tumors that are known to display broad phenotypic overlap with their identically named müllerian counterparts. Herein, we assess the utility of AMACR in distinguishing endometrial clear cell carcinomas (CCCs) from endometrial serous carcinomas (ESCs) and endometrial endometrioid carcinomas (EECs). A total of 111 endometrial carcinomas in a tissue microarray, including 49 CCCs, 13 ESCs, and 49 EECs, were assessed for AMACR immunoreactivity, with results scored semiquantitatively (scores 0, 1+, 2+, 3+ for 0%, 1%-5%, 6%-50%, >50% immunoreactive cells, respectively). Fifty (45%) of the 111 carcinomas were AMACR positive, with the following score distribution: CCC: 0 (n = 12), 1+ (n = 12), 2+ (n = 3), 3+ (n = 22); EEC: 0 (n = 38), 1+ (n = 4), 2+ (n = 4), 3+ (n = 3); ESC: 0 (n = 11), 1+ (n = 1), 2+ (n = 0), 3+ (n = 1). AMACR expression was significantly more frequent in CCC (75%) than in ESC (15%) or EEC (22%); P < .0001. The sensitivity and specificity of AMACR expression in classifying a carcinoma as CCC were 0.75 (95% confidence interval [CI], 0.61-0.86) and 0.79 (95% CI, 0.66-0.88), respectively, with an odds ratio of 11.62 (95% CI, 5-28; P < .001) and an area under the curve of 0.79 (95% CI, 0.68-0.88). These findings indicate that AMACR expression is strongly associated with CCC and displays a relatively robust diagnostic test performance. However, its practical utility may be limited by the focal nature of its expression in 32% of the AMACR-positive CCC cases as well as its expression in 15% to 22% of the non-CCC histotypes.
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Obstetrics and Gynecology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Electronic address: oluwolefadare@yahoo.com.
authors.forename: Oluwole
authors.initials: O
authors.lastname: Fadare
authors.forename: Vinita
authors.initials: V
authors.lastname: Parkash
authors.forename: Katja
authors.initials: K
authors.lastname: Gwin
authors.forename: Krisztina Z
authors.initials: KZ
authors.lastname: Hanley
authors.forename: Elke A
authors.initials: EA
authors.lastname: Jarboe
authors.forename: Sharon X
authors.initials: SX
authors.lastname: Liang
authors.forename: Charles M
authors.initials: CM
authors.lastname: Quick
authors.forename: Wenxin
authors.initials: W
authors.lastname: Zheng
authors.forename: Kojo R
authors.initials: KR
authors.lastname: Rawish
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Hecht
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Desouki
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018269:Carcinoma, Endometrioid / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D003937:Diagnosis, Differential; D016889:Endometrial Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D019998:Racemases and Epimerases / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase
keywords: AMACR; Alpha-methylacyl-CoA-racemase; Endometrial clear cell carcinoma; Immunohistochemistry; p504s