Utility of α-methylacyl-coenzyme-A racemase (p504s) immunohistochemistry in distinguishing endometrial clear cell carcinomas from serous and endometrioid carcinomas

Oluwole Fadare, Vinita Parkash, Katja Gwin, Krisztina Z. Hanley, Elke A. Jarboe, Sharon X. Liang, Charles M. Quick, Wenxin Zheng, Kojo R. Rawish, Jonathan L. Hecht, Mohamed M. Desouki

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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.

Original languageEnglish (US)
Pages (from-to)2814-2821
Number of pages8
JournalHuman Pathology
Volume44
Issue number12
DOIs
StatePublished - Dec 2013

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Endometrioid Carcinoma
Racemases and Epimerases
Coenzymes
Endometrial Neoplasms
Immunohistochemistry
Carcinoma
Confidence Intervals
Routine Diagnostic Tests
Area Under Curve
Urinary Bladder
Odds Ratio

Keywords

  • Alpha-methylacyl-CoA-racemase
  • AMACR
  • Endometrial clear cell carcinoma
  • Immunohistochemistry
  • p504s

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Utility of α-methylacyl-coenzyme-A racemase (p504s) immunohistochemistry in distinguishing endometrial clear cell carcinomas from serous and endometrioid carcinomas. / Fadare, Oluwole; Parkash, Vinita; Gwin, Katja; Hanley, Krisztina Z.; Jarboe, Elke A.; Liang, Sharon X.; Quick, Charles M.; Zheng, Wenxin; Rawish, Kojo R.; Hecht, Jonathan L.; Desouki, Mohamed M.

In: Human Pathology, Vol. 44, No. 12, 12.2013, p. 2814-2821.

Research output: Contribution to journalArticle

Fadare, Oluwole ; Parkash, Vinita ; Gwin, Katja ; Hanley, Krisztina Z. ; Jarboe, Elke A. ; Liang, Sharon X. ; Quick, Charles M. ; Zheng, Wenxin ; Rawish, Kojo R. ; Hecht, Jonathan L. ; Desouki, Mohamed M. / Utility of α-methylacyl-coenzyme-A racemase (p504s) immunohistochemistry in distinguishing endometrial clear cell carcinomas from serous and endometrioid carcinomas. In: Human Pathology. 2013 ; Vol. 44, No. 12. pp. 2814-2821.
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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 m{\"u}llerian 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.",
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AU - Quick, Charles M.

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AU - Hecht, Jonathan L.

AU - Desouki, Mohamed M.

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N2 - 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.

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