Skip to main content
Erschienen in: Virchows Archiv 1/2011

01.07.2011 | Original Article

Alpha-methylacyl-CoA racemase (AMACR) expression in epithelial ovarian cancer

verfasst von: Aurelia Noske, Anne-Katrin Zimmermann, Rosmarie Caduff, Zsuzsanna Varga, Daniel Fink, Holger Moch, Glen Kristiansen

Erschienen in: Virchows Archiv | Ausgabe 1/2011

Einloggen, um Zugang zu erhalten

Abstract

Alpha-methylacyl-CoA racemase (AMACR) is involved in the cellular metabolism of fatty acids. It is a prognostic factor in prostate and colorectal cancer. So far, little is known about its expression and prognostic role in ovarian cancer. We investigated the expression of AMACR in a total of 420 ovarian tumors (388 carcinomas, 32 borderline tumors) by immunohistochemistry on tissue microarrays of two independent patient cohorts. In both cohorts, cytoplasmic AMACR expression was identified in 11.8% (16/136) and 5.4% (13/239), respectively, of the ovarian carcinomas. In contrast, borderline tumors did not show any AMACR expression. AMACR expression was significantly associated with histological subtype, FIGO stage, and grade in one cohort and low estrogen receptor levels in the other cohort. In univariate analysis, AMACR expression was significantly associated with poor overall survival (log rank, p = 0.006) and an independent prognostic factor in a multivariate analysis (HR 3.3; CI 1.3–7.9; p = 0.008) but could not be verified in the second cohort. Unlike in other tumor entities, AMACR expression does not seem to have an unequivocal prognostic impact in ovarian cancer. The prevalence may limit the value of AMACR for the differential diagnosis between metastatic colorectal carcinomas and primary ovarian carcinomas, whereas the association with estrogen receptor expression deserves further studies.
Literatur
1.
Zurück zum Zitat Schulz M, Lahmann PH, Riboli E, Boeing H (2004) Dietary determinants of epithelial ovarian cancer: a review of the epidemiologic literature. Nutr Cancer 50:120–140PubMedCrossRef Schulz M, Lahmann PH, Riboli E, Boeing H (2004) Dietary determinants of epithelial ovarian cancer: a review of the epidemiologic literature. Nutr Cancer 50:120–140PubMedCrossRef
2.
Zurück zum Zitat Kolahdooz F, Ibiebele TI, van der Pols JC, Webb PM (2009) Dietary patterns and ovarian cancer risk. Am J Clin Nutr 89:297–304PubMedCrossRef Kolahdooz F, Ibiebele TI, van der Pols JC, Webb PM (2009) Dietary patterns and ovarian cancer risk. Am J Clin Nutr 89:297–304PubMedCrossRef
3.
Zurück zum Zitat Amery L, Fransen M, De Nys K, Mannaerts GP, Van Veldhoven PP (2000) Mitochondrial and peroxisomal targeting of 2-methylacyl-CoA racemase in humans. J Lipid Res 41:1752–1759PubMed Amery L, Fransen M, De Nys K, Mannaerts GP, Van Veldhoven PP (2000) Mitochondrial and peroxisomal targeting of 2-methylacyl-CoA racemase in humans. J Lipid Res 41:1752–1759PubMed
4.
Zurück zum Zitat Xu J, Thornburg T, Turner AR, Vitolins M, Case D, Shadle J, Hinson L, Sun J, Liu W, Chang B, Adams TS, Zheng SL, Torti FM (2005) Serum levels of phytanic acid are associated with prostate cancer risk. Prostate 63:209–214PubMedCrossRef Xu J, Thornburg T, Turner AR, Vitolins M, Case D, Shadle J, Hinson L, Sun J, Liu W, Chang B, Adams TS, Zheng SL, Torti FM (2005) Serum levels of phytanic acid are associated with prostate cancer risk. Prostate 63:209–214PubMedCrossRef
5.
Zurück zum Zitat Mobley JA, Leav I, Zielie P, Wotkowitz C, Evans J, Lam YW, L’Esperance BS, Jiang Z, Ho SM (2003) Branched fatty acids in dairy and beef products markedly enhance alpha-methylacyl-CoA racemase expression in prostate cancer cells in vitro. Cancer Epidemiol Biomarkers Prev 12:775–783PubMed Mobley JA, Leav I, Zielie P, Wotkowitz C, Evans J, Lam YW, L’Esperance BS, Jiang Z, Ho SM (2003) Branched fatty acids in dairy and beef products markedly enhance alpha-methylacyl-CoA racemase expression in prostate cancer cells in vitro. Cancer Epidemiol Biomarkers Prev 12:775–783PubMed
6.
Zurück zum Zitat Xu J, Stolk JA, Zhang X, Silva SJ, Houghton RL, Matsumura M, Vedvick TS, Leslie KB, Badaro R, Reed SG (2000) Identification of differentially expressed genes in human prostate cancer using subtraction and microarray. Cancer Res 60:1677–1682PubMed Xu J, Stolk JA, Zhang X, Silva SJ, Houghton RL, Matsumura M, Vedvick TS, Leslie KB, Badaro R, Reed SG (2000) Identification of differentially expressed genes in human prostate cancer using subtraction and microarray. Cancer Res 60:1677–1682PubMed
7.
Zurück zum Zitat Jiang Z, Wu CL, Woda BA, Dresser K, Xu J, Fanger GR, Yang XJ (2002) P504s/alpha-methylacyl-CoA racemase: a useful marker for diagnosis of small foci of prostatic carcinoma on needle biopsy. Am J Surg Pathol 26:1169–1174PubMedCrossRef Jiang Z, Wu CL, Woda BA, Dresser K, Xu J, Fanger GR, Yang XJ (2002) P504s/alpha-methylacyl-CoA racemase: a useful marker for diagnosis of small foci of prostatic carcinoma on needle biopsy. Am J Surg Pathol 26:1169–1174PubMedCrossRef
8.
Zurück zum Zitat Kristiansen G, Fritzsche FR, Wassermann K, Jager C, Tolls A, Lein M, Stephan C, Jung K, Pilarsky C, Dietel M, Moch H (2008) Golph2 protein expression as a novel tissue biomarker for prostate cancer: implications for tissue-based diagnostics. Br J Cancer 99:939–948PubMedCrossRef Kristiansen G, Fritzsche FR, Wassermann K, Jager C, Tolls A, Lein M, Stephan C, Jung K, Pilarsky C, Dietel M, Moch H (2008) Golph2 protein expression as a novel tissue biomarker for prostate cancer: implications for tissue-based diagnostics. Br J Cancer 99:939–948PubMedCrossRef
9.
Zurück zum Zitat Jiang Z, Fanger GR, Woda BA, Banner BF, Algate P, Dresser K, Xu J, Chu PG (2003) Expression of alpha-methylacyl-CoA racemase (p504s) in various malignant neoplasms and normal tissues: a study of 761 cases. Hum Pathol 34:792–796PubMedCrossRef Jiang Z, Fanger GR, Woda BA, Banner BF, Algate P, Dresser K, Xu J, Chu PG (2003) Expression of alpha-methylacyl-CoA racemase (p504s) in various malignant neoplasms and normal tissues: a study of 761 cases. Hum Pathol 34:792–796PubMedCrossRef
10.
Zurück zum Zitat Gunia S, May M, Scholmann K, Storkel S, Hoschke B, Koch S, Dietel M, Kristiansen G (2008) Expression of alpha-methylacyl-CoA racemase correlates with histopathologic grading in noninvasive bladder cancer. Virchows Arch 453:165–170PubMedCrossRef Gunia S, May M, Scholmann K, Storkel S, Hoschke B, Koch S, Dietel M, Kristiansen G (2008) Expression of alpha-methylacyl-CoA racemase correlates with histopathologic grading in noninvasive bladder cancer. Virchows Arch 453:165–170PubMedCrossRef
11.
Zurück zum Zitat Lin A, Weiser MR, Klimstra DS, Paty PB, Tang LH, Al-Ahmadie H, Hoo Park S, Guillem JG, Temple L, Wong WD, Gerald WL, Shia J (2007) Differential expression of alpha-methylacyl-coenzyme A racemase in colorectal carcinoma bears clinical and pathologic significance. Hum Pathol 38:850–856PubMedCrossRef Lin A, Weiser MR, Klimstra DS, Paty PB, Tang LH, Al-Ahmadie H, Hoo Park S, Guillem JG, Temple L, Wong WD, Gerald WL, Shia J (2007) Differential expression of alpha-methylacyl-coenzyme A racemase in colorectal carcinoma bears clinical and pathologic significance. Hum Pathol 38:850–856PubMedCrossRef
12.
Zurück zum Zitat Rubin MA, Bismar TA, Andren O, Mucci L, Kim R, Shen R, Ghosh D, Wei JT, Chinnaiyan AM, Adami HO, Kantoff PW, Johansson JE (2005) Decreased alpha-methylacyl CoA racemase expression in localized prostate cancer is associated with an increased rate of biochemical recurrence and cancer-specific death. Cancer Epidemiol Biomarkers Prev 14:1424–1432PubMedCrossRef Rubin MA, Bismar TA, Andren O, Mucci L, Kim R, Shen R, Ghosh D, Wei JT, Chinnaiyan AM, Adami HO, Kantoff PW, Johansson JE (2005) Decreased alpha-methylacyl CoA racemase expression in localized prostate cancer is associated with an increased rate of biochemical recurrence and cancer-specific death. Cancer Epidemiol Biomarkers Prev 14:1424–1432PubMedCrossRef
13.
Zurück zum Zitat Zhou M, Chinnaiyan AM, Kleer CG, Lucas PC, Rubin MA (2002) Alpha-methylacyl-CoA racemase: a novel tumor marker over-expressed in several human cancers and their precursor lesions. Am J Surg Pathol 26:926–931PubMedCrossRef Zhou M, Chinnaiyan AM, Kleer CG, Lucas PC, Rubin MA (2002) Alpha-methylacyl-CoA racemase: a novel tumor marker over-expressed in several human cancers and their precursor lesions. Am J Surg Pathol 26:926–931PubMedCrossRef
14.
Zurück zum Zitat Nassar A, Amin MB, Sexton DG, Cohen C (2005) Utility of alpha-methylacyl coenzyme A racemase (p504s antibody) as a diagnostic immunohistochemical marker for cancer. Appl Immunohistochem Mol Morphol 13:252–255PubMedCrossRef Nassar A, Amin MB, Sexton DG, Cohen C (2005) Utility of alpha-methylacyl coenzyme A racemase (p504s antibody) as a diagnostic immunohistochemical marker for cancer. Appl Immunohistochem Mol Morphol 13:252–255PubMedCrossRef
15.
16.
Zurück zum Zitat Moch H, Schraml P, Bubendorf L, Mirlacher M, Kononen J, Gasser T, Mihatsch MJ, Kallioniemi OP, Sauter G (1999) High-throughput tissue microarray analysis to evaluate genes uncovered by cDNA microarray screening in renal cell carcinoma. Am J Pathol 154:981–986PubMedCrossRef Moch H, Schraml P, Bubendorf L, Mirlacher M, Kononen J, Gasser T, Mihatsch MJ, Kallioniemi OP, Sauter G (1999) High-throughput tissue microarray analysis to evaluate genes uncovered by cDNA microarray screening in renal cell carcinoma. Am J Pathol 154:981–986PubMedCrossRef
17.
Zurück zum Zitat Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP (1998) Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 4:844–847PubMedCrossRef Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP (1998) Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 4:844–847PubMedCrossRef
18.
Zurück zum Zitat Schraml P, Schwerdtfeger G, Burkhalter F, Raggi A, Schmidt D, Ruffalo T, King W, Wilber K, Mihatsch MJ, Moch H (2003) Combined array comparative genomic hybridization and tissue microarray analysis suggest PAK1 at 11q13.5-q14 as a critical oncogene target in ovarian carcinoma. Am J Pathol 163:985–992PubMedCrossRef Schraml P, Schwerdtfeger G, Burkhalter F, Raggi A, Schmidt D, Ruffalo T, King W, Wilber K, Mihatsch MJ, Moch H (2003) Combined array comparative genomic hybridization and tissue microarray analysis suggest PAK1 at 11q13.5-q14 as a critical oncogene target in ovarian carcinoma. Am J Pathol 163:985–992PubMedCrossRef
19.
Zurück zum Zitat Langner C, Rupar G, Leibl S, Hutterer G, Chromecki T, Hoefler G, Rehak P, Zigeuner R (2006) Alpha-methylacyl-CoA racemase (AMACR/p504s) protein expression in urothelial carcinoma of the upper urinary tract correlates with tumour progression. Virchows Arch 448:325–330PubMedCrossRef Langner C, Rupar G, Leibl S, Hutterer G, Chromecki T, Hoefler G, Rehak P, Zigeuner R (2006) Alpha-methylacyl-CoA racemase (AMACR/p504s) protein expression in urothelial carcinoma of the upper urinary tract correlates with tumour progression. Virchows Arch 448:325–330PubMedCrossRef
20.
Zurück zum Zitat Logani S, Oliva E, Arnell PM, Amin MB, Young RH (2005) Use of novel immunohistochemical markers expressed in colonic adenocarcinoma to distinguish primary ovarian tumors from metastatic colorectal carcinoma. Mod Pathol 18:19–25PubMedCrossRef Logani S, Oliva E, Arnell PM, Amin MB, Young RH (2005) Use of novel immunohistochemical markers expressed in colonic adenocarcinoma to distinguish primary ovarian tumors from metastatic colorectal carcinoma. Mod Pathol 18:19–25PubMedCrossRef
21.
Zurück zum Zitat Kuefer R, Varambally S, Zhou M, Lucas PC, Loeffler M, Wolter H, Mattfeldt T, Hautmann RE, Gschwend JE, Barrette TR, Dunn RL, Chinnaiyan AM, Rubin MA (2002) Alpha-methylacyl-CoA racemase: expression levels of this novel cancer biomarker depend on tumor differentiation. Am J Pathol 161:841–848PubMedCrossRef Kuefer R, Varambally S, Zhou M, Lucas PC, Loeffler M, Wolter H, Mattfeldt T, Hautmann RE, Gschwend JE, Barrette TR, Dunn RL, Chinnaiyan AM, Rubin MA (2002) Alpha-methylacyl-CoA racemase: expression levels of this novel cancer biomarker depend on tumor differentiation. Am J Pathol 161:841–848PubMedCrossRef
22.
Zurück zum Zitat Witkiewicz AK, Varambally S, Shen R, Mehra R, Sabel MS, Ghosh D, Chinnaiyan AM, Rubin MA, Kleer CG (2005) Alpha-methylacyl-CoA racemase protein expression is associated with the degree of differentiation in breast cancer using quantitative image analysis. Cancer Epidemiol Biomarkers Prev 14:1418–1423PubMedCrossRef Witkiewicz AK, Varambally S, Shen R, Mehra R, Sabel MS, Ghosh D, Chinnaiyan AM, Rubin MA, Kleer CG (2005) Alpha-methylacyl-CoA racemase protein expression is associated with the degree of differentiation in breast cancer using quantitative image analysis. Cancer Epidemiol Biomarkers Prev 14:1418–1423PubMedCrossRef
23.
Zurück zum Zitat Issa RM, Lebeau A, Grob T, Holst F, Moch H, Terracciano L, Choschzick M, Sauter G, Simon R (2009) Estrogen receptor gene amplification occurs rarely in ovarian cancer. Mod Pathol 22:191–196PubMedCrossRef Issa RM, Lebeau A, Grob T, Holst F, Moch H, Terracciano L, Choschzick M, Sauter G, Simon R (2009) Estrogen receptor gene amplification occurs rarely in ovarian cancer. Mod Pathol 22:191–196PubMedCrossRef
24.
Zurück zum Zitat Takahara K, Azuma H, Sakamoto T, Kiyama S, Inamoto T, Ibuki N, Nishida T, Nomi H, Ubai T, Segawa N, Katsuoka Y (2009) Conversion of prostate cancer from hormone independency to dependency due to AMACR inhibition: involvement of increased AR expression and decreased IGF1 expression. Anticancer Res 29:2497–2505PubMed Takahara K, Azuma H, Sakamoto T, Kiyama S, Inamoto T, Ibuki N, Nishida T, Nomi H, Ubai T, Segawa N, Katsuoka Y (2009) Conversion of prostate cancer from hormone independency to dependency due to AMACR inhibition: involvement of increased AR expression and decreased IGF1 expression. Anticancer Res 29:2497–2505PubMed
25.
Zurück zum Zitat McLemore MR, Miaskowski C, Aouizerat BE, Chen LM, Dodd MJ (2009) Epidemiological and genetic factors associated with ovarian cancer. Cancer Nurs 32:281–288, quiz 289–290PubMedCrossRef McLemore MR, Miaskowski C, Aouizerat BE, Chen LM, Dodd MJ (2009) Epidemiological and genetic factors associated with ovarian cancer. Cancer Nurs 32:281–288, quiz 289–290PubMedCrossRef
26.
Zurück zum Zitat McCann SE, Freudenheim JL, Marshall JR, Graham S (2003) Risk of human ovarian cancer is related to dietary intake of selected nutrients, phytochemicals and food groups. J Nutr 133:1937–1942PubMed McCann SE, Freudenheim JL, Marshall JR, Graham S (2003) Risk of human ovarian cancer is related to dietary intake of selected nutrients, phytochemicals and food groups. J Nutr 133:1937–1942PubMed
Metadaten
Titel
Alpha-methylacyl-CoA racemase (AMACR) expression in epithelial ovarian cancer
verfasst von
Aurelia Noske
Anne-Katrin Zimmermann
Rosmarie Caduff
Zsuzsanna Varga
Daniel Fink
Holger Moch
Glen Kristiansen
Publikationsdatum
01.07.2011
Verlag
Springer-Verlag
Erschienen in
Virchows Archiv / Ausgabe 1/2011
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-011-1095-9

Weitere Artikel der Ausgabe 1/2011

Virchows Archiv 1/2011 Zur Ausgabe

Neu im Fachgebiet Pathologie