α-Methylacyl-CoA Racemase: Expression Levels of this Novel Cancer Biomarker Depend on Tumor Differentiation

Abstract

alpha-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.

Use of novel immunohistochemical markers expressed in colonic adenocarcinoma to distinguish primary ovarian tumors from metastatic colorectal carcinoma

“…There is some suggestion that the protein expression of P504S is related to the grade of the tumor with the highest expression in a tubular adenoma and decreased expression in high-grade tumors. 15 Since metastatic tumors are more likely to be high grade, the decreased expression of P504S in the metastatic colorectal carcinomas in our study is not surprising.…”

“…16,32 The expression of this protein in cancer precursor lesions such as high-grade prostatic intraepithelial neoplasia and colorectal adenoma suggests that it has a role in early carcinogenesis. 15 The expression of this protein in ovarian carcinoma has not been formally studied and limited information is available on its expression profile in epithelial tumors of the ovary of different histologic subtypes. In this study, 32% of metastatic colonic adenocarcinomas to the ovary showed diffuse expression of P504S as compared to none of the primary ovarian tumors.…”

“…14 a-Methylacyl-CoA racemase (AMACR) or P504S, an enzyme involved in bile acid biosynthesis, has been shown to be a highly sensitive marker for colorectal carcinomas, although its expression has been shown to be directly related to the grade of the tumor. 15,16 The use of these antibodies in clinical practice to identify a metastatic tumor as colorectal in origin when the primary site may not be clinically apparent is of great potential and provides a useful addition to CK7 and CK20. In this study, we evaluated the utility of a panel of immunohistochemical stains, CDX2, bcatenin and P504S, in distinguishing primary mucinous and endometrioid adenocarcinoma from metastatic colorectal adenocarcinoma to the ovary.…”

Quadriplex model enhances urine-based detection of prostate cancer

“…Consistent with other studies we also confirmed the idea of using AMACR as a marker of progression as its expression was increased in advanced stages of the cancer. 24,25 The multiplex model, which was composed of all seven biomarkers including serum PSA, showed significantly good AUC (AUC ¼ 0.744). Further, as this model would not be cost-and labor-effective, three additional models were generated.…”

Detection and expression of human BK virus sequences in neoplastic prostate tissues

“…In spite of the availability of biomarkers for PCA, the basic molecular mechanisms regulating its development and progression are still very poorly understood (Nupponen and Visakorpi, 1999;Jiang et al, 2001;Kuefer et al, 2002;Rubin et al, 2002;Varambally et al, 2002;Yang et al, 2002). Recognition of the precursor lesions of PCA has become a primary focus in recent years.…”