α-Methylacyl-CoA racemase: Expression levels of this novel cancer biomarker depend on tumor differentiation

Rainer Kuefer, Sooryanarayana Varambally, Ming Zhou, Peter C. Lucas, Martin Loeffler, Hubertus Wolter, Torsten Mattfeldt, Richard E. Hautmann, Juergen E. Gschwend, Terrence R. Barrette, Rodney L. Dunn, Arul M. Chinnaiyan, Mark A. Rubin

Research output: Contribution to journalArticle

113 Scopus citations

Abstract

α-Methylacyl-CoA racemase (AMACR) has previously been shown to be a highly sensitive marker for colorectal and clinically localized prostate cancer (PCa). However, AMACR expression was down-regulated at the transcript and protein level in hormone-refractory metastatic PCa, suggesting a hormone-dependent expression of AMACR. To further explore the hypothesis that AMACR is hormone regulated and plays a role in PCa progression AMACR protein expression was characterized in a broad range of PCa samples treated with variable amounts and lengths of exogenous anti-androgens. Analysis included standard slides and high-density tissue microarrays. AMACR protein expression was significantly increased in localized hormone-naive PCa as compared to benign (P < 0.001). Mean AMACR expression was lower in tissue samples from patients who had received neoadjuvant hormone treatment but still higher compared to hormone-refractory metastases. The hormone-sensitive tumor cell line, LNCaP, demonstrated stronger AMACR expression by Western blot analysis than the poorly differentiated cell lines DU-145 and PC-3. AMACR protein expression in cells after exposure to anti-androgen treatment was unchanged, whereas prostate-specific antigen, known to be androgen-regulated, demonstrated decreased protein expression. Surprisingly, this data suggests that AMACR expression is not regulated by androgens. Examination of colorectal cancer, which is not hormone regulated, demonstrated high levels of AMACR expression in well to moderately differentiated tumors and weak expression in anaplastic colorectal cancers. Taken together, these data suggest that AMACR expression is not hormone-dependent but may in fact be a marker of tumor differentiation.

Original languageEnglish (US)
Article number64244
Pages (from-to)841-848
Number of pages8
JournalAmerican Journal of Pathology
Volume161
Issue number3
DOIs
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Kuefer, R., Varambally, S., Zhou, M., Lucas, P. C., Loeffler, M., Wolter, H., Mattfeldt, T., Hautmann, R. E., Gschwend, J. E., Barrette, T. R., Dunn, R. L., Chinnaiyan, A. M., & Rubin, M. A. (2002). α-Methylacyl-CoA racemase: Expression levels of this novel cancer biomarker depend on tumor differentiation. American Journal of Pathology, 161(3), 841-848. [64244]. https://doi.org/10.1016/S0002-9440(10)64244-7