Comparative analysis of Napsin A, alpha-methylacyl-coenzyme A racemase (AMACR, P504S), and hepatocyte nuclear factor 1 beta as diagnostic markers of ovarian clear cell carcinoma: An immunohistochemical study of 279 ovarian tumours

Oluwole Fadare, Chengquan Zhao, Dineo Khabele, Vinita Parkash, Charles M. Quick, Katja Gwin, Mohamed M. Desouki

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Napsin A and a-methylacyl-coenzyme A racemase (AMACR, P504S) have recently been described as being frequently expressed in clear cell carcinomas (CCC) of the gynecological tract. The present study was conducted to assess the test performance of these newer markers relative to the more traditional marker, hepatocyte nuclear factor 1β (HNF1β), in a large and histotypically diverse dataset. A total of 279 ovarian tumours in tissue microarrays were immunohisto-chemically assessed for the expression of Napsin A, AMACR and HNF1 β. HNF1β, Napsin A and AMACR were expressed in 92%, 82% and 63% of 65 CCC, 7%, 1% and 1% of 101 serous carcinomas, 37%, 5.3% and 0% of 19 endometrioid carcinomas, 60%, 0% and 0% of 45 mucinous tumours, 100%, 0% and 0% of seven yolk sac tumours, and 0%, 16.7% and 16.7% of six steroid cell tumours NOS, respectively. All other tumours, including 18 adult-type granulosa cell tumours, eight dysgerminomas and nine other miscellaneous tumour types were negative for all three markers. Using a benchmark of ≥ 1% of tumour cells for positivity and CCC as the diagnostic end-point, the sensitivity, specificity, negative predictive value and positive predictive value of Napsin A expression were 0.82, 0.99, 0.94, and 0.98, respectively (odds ratio 439, p< 0.0001). Respective parameters were 0.92, 0.79, 0.97, and 0.58 (odds ratio 44, p< 0.0001) for HNF1β and 0.63, 0.99, 0.89, and 0.5 (odds ratio 112, p< 0.0001) for AMACR. The combination of any two positive markers, irrespective of the staining pattern of the third, significantly predicted the CCC histotype in every analytic scenario. In summary, HNF1 b is highly sensitive but is suboptimally specific in isolation, whereas AMACR is highly specific but is suboptimally sensitive. Napsin A is specific but of intermediate sensitivity. Napsin A, AMACR and HNF1b are all viable markers of CCC that can be deployed as components of larger panels when CCC is a diagnostic consideration.

Original languageEnglish (US)
Pages (from-to)105-111
Number of pages7
JournalPathology
Volume47
Issue number2
DOIs
StatePublished - 2015

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Hepatocyte Nuclear Factor 1-beta
Racemases and Epimerases
Coenzyme A
Hepatocyte Nuclear Factor 1
Carcinoma
Neoplasms
Odds Ratio
Dysgerminoma
Granulosa Cell Tumor
Endodermal Sinus Tumor
Endometrioid Carcinoma
Benchmarking
Steroids
Staining and Labeling

Keywords

  • A-methylacyl-coenzyme A racemase
  • AMACR
  • Clear cell carcinoma
  • Hepatocyte nuclear factor 1β
  • HNF1β
  • Napsin A
  • Ovary
  • P504S

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Comparative analysis of Napsin A, alpha-methylacyl-coenzyme A racemase (AMACR, P504S), and hepatocyte nuclear factor 1 beta as diagnostic markers of ovarian clear cell carcinoma : An immunohistochemical study of 279 ovarian tumours. / Fadare, Oluwole; Zhao, Chengquan; Khabele, Dineo; Parkash, Vinita; Quick, Charles M.; Gwin, Katja; Desouki, Mohamed M.

In: Pathology, Vol. 47, No. 2, 2015, p. 105-111.

Research output: Contribution to journalArticle

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abstract = "Napsin A and a-methylacyl-coenzyme A racemase (AMACR, P504S) have recently been described as being frequently expressed in clear cell carcinomas (CCC) of the gynecological tract. The present study was conducted to assess the test performance of these newer markers relative to the more traditional marker, hepatocyte nuclear factor 1β (HNF1β), in a large and histotypically diverse dataset. A total of 279 ovarian tumours in tissue microarrays were immunohisto-chemically assessed for the expression of Napsin A, AMACR and HNF1 β. HNF1β, Napsin A and AMACR were expressed in 92{\%}, 82{\%} and 63{\%} of 65 CCC, 7{\%}, 1{\%} and 1{\%} of 101 serous carcinomas, 37{\%}, 5.3{\%} and 0{\%} of 19 endometrioid carcinomas, 60{\%}, 0{\%} and 0{\%} of 45 mucinous tumours, 100{\%}, 0{\%} and 0{\%} of seven yolk sac tumours, and 0{\%}, 16.7{\%} and 16.7{\%} of six steroid cell tumours NOS, respectively. All other tumours, including 18 adult-type granulosa cell tumours, eight dysgerminomas and nine other miscellaneous tumour types were negative for all three markers. Using a benchmark of ≥ 1{\%} of tumour cells for positivity and CCC as the diagnostic end-point, the sensitivity, specificity, negative predictive value and positive predictive value of Napsin A expression were 0.82, 0.99, 0.94, and 0.98, respectively (odds ratio 439, p< 0.0001). Respective parameters were 0.92, 0.79, 0.97, and 0.58 (odds ratio 44, p< 0.0001) for HNF1β and 0.63, 0.99, 0.89, and 0.5 (odds ratio 112, p< 0.0001) for AMACR. The combination of any two positive markers, irrespective of the staining pattern of the third, significantly predicted the CCC histotype in every analytic scenario. In summary, HNF1 b is highly sensitive but is suboptimally specific in isolation, whereas AMACR is highly specific but is suboptimally sensitive. Napsin A is specific but of intermediate sensitivity. Napsin A, AMACR and HNF1b are all viable markers of CCC that can be deployed as components of larger panels when CCC is a diagnostic consideration.",
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T2 - An immunohistochemical study of 279 ovarian tumours

AU - Fadare, Oluwole

AU - Zhao, Chengquan

AU - Khabele, Dineo

AU - Parkash, Vinita

AU - Quick, Charles M.

AU - Gwin, Katja

AU - Desouki, Mohamed M.

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N2 - Napsin A and a-methylacyl-coenzyme A racemase (AMACR, P504S) have recently been described as being frequently expressed in clear cell carcinomas (CCC) of the gynecological tract. The present study was conducted to assess the test performance of these newer markers relative to the more traditional marker, hepatocyte nuclear factor 1β (HNF1β), in a large and histotypically diverse dataset. A total of 279 ovarian tumours in tissue microarrays were immunohisto-chemically assessed for the expression of Napsin A, AMACR and HNF1 β. HNF1β, Napsin A and AMACR were expressed in 92%, 82% and 63% of 65 CCC, 7%, 1% and 1% of 101 serous carcinomas, 37%, 5.3% and 0% of 19 endometrioid carcinomas, 60%, 0% and 0% of 45 mucinous tumours, 100%, 0% and 0% of seven yolk sac tumours, and 0%, 16.7% and 16.7% of six steroid cell tumours NOS, respectively. All other tumours, including 18 adult-type granulosa cell tumours, eight dysgerminomas and nine other miscellaneous tumour types were negative for all three markers. Using a benchmark of ≥ 1% of tumour cells for positivity and CCC as the diagnostic end-point, the sensitivity, specificity, negative predictive value and positive predictive value of Napsin A expression were 0.82, 0.99, 0.94, and 0.98, respectively (odds ratio 439, p< 0.0001). Respective parameters were 0.92, 0.79, 0.97, and 0.58 (odds ratio 44, p< 0.0001) for HNF1β and 0.63, 0.99, 0.89, and 0.5 (odds ratio 112, p< 0.0001) for AMACR. The combination of any two positive markers, irrespective of the staining pattern of the third, significantly predicted the CCC histotype in every analytic scenario. In summary, HNF1 b is highly sensitive but is suboptimally specific in isolation, whereas AMACR is highly specific but is suboptimally sensitive. Napsin A is specific but of intermediate sensitivity. Napsin A, AMACR and HNF1b are all viable markers of CCC that can be deployed as components of larger panels when CCC is a diagnostic consideration.

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KW - Ovary

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