Increased fatty acid synthase expression in prostate biopsy cores predicts higher Gleason score in radical prostatectomy specimen

BMC Clinical Pathology

Keiichi Iwaya²  Kosuke Miyai²  Tomohiko Asano¹  Keiichi Ito¹  Kenji Kuroda¹  Akio Horiguchi¹  Shinsuke Hamada¹ 

[1] Department of Urology, National Defense Medical College, 3-2 Namiki, Tokorozawa-City, Saitama 359-8513, Japan;Department of Basic Pathology, National Defense Medical College, Tokorozawa-City, Saitama, Japan

关键词: Gleason score;    Biopsy core;    Prostate cancer;    Fatty acid synthase;   

Others  :  1084664
DOI  :  10.1186/1472-6890-14-3

 received in 2013-07-22, accepted in 2014-01-09,  发布年份 2014

【 摘 要 】

Background

Fatty acid synthase (FAS) is highly expressed in various types of cancer, and elevated expression of FAS has been suggested to be a predictor of tumor aggressiveness and poor prognosis. We examined whether FAS expression in prostate biopsy cores could predict the pathological characteristics of radical prostatectomy (RP) specimens.

Methods

Paraffin-embedded prostate biopsy cores, obtained from 102 patients who subsequently underwent RP, were immunostained with polyclonal anti-FAS antibody. The staining intensity was categorized into non-staining, weak, moderate, and strong. Tumors with moderate or strong immunostaining were considered to show high FAS expression, and other tumors were considered to show low FAS expression. The relation between the FAS expression status in biopsy cores and pathological parameters in RP specimens was analyzed.

Results

The FAS expression in the biopsy cores of 64 of the 102 tumors (63%) was high, whereas it was low in the biopsy cores of the other 38 tumors (37%). High FAS expression was significantly associated with Gleason Score (GS) ≥ 7 in RP specimens (p< 0.0001). In multivariable logistic regression analyses, GS ≥7 in biopsy cores (p <0.0001), higher preoperative PSA (p = 0.0194), and high FAS expression (p = 0.0004) were independent predictors of GS ≥ 7 in the RP specimen.

Conclusions

Increased FAS expression in prostate biopsy cores could be a novel parameter for predicting higher GS in RP specimens. The treatment strategy for patients with high FAS expression in prostate biopsy cores should be carefully determined.

【 授权许可】

   
2014 Hamada et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Menendez JA, Lupu R: Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer 2007, 7:763-777.
• [2]Flavin R, Peluso S, Nguyen PL, Loda M: Fatty acid synthase as a potential therapeutic target in cancer. Future Oncol 2010, 6:551-562.
• [3]Kuhajda FP: Fatty acid synthase and cancer: new application of an old pathway. Cancer Res 2006, 66:5977-5980.
• [4]Shurbaji MS, Kalbfleisch JH, Thurmond TS: Immunohistochemical detection of a fatty acid synthase (OA-519) as a predictor of progression of prostate cancer. Hum Pathol 1996, 27:917-921.
• [5]Takahiro T, Shinichi K, Toshimitsu S: Expression of fatty acid synthase as a prognostic indicator in soft tissue sarcomas. Clin Cancer Res 2003, 9:2204-2212.
• [6]Bandyopadhyay S, Pai SK, Watabe M, Gross SC, Hirota S, Hosobe S, Tsukada T, Miura K, Saito K, Markwell SJ, et al.: FAS expression inversely correlates with PTEN level in prostate cancer and a PI 3-kinase inhibitor synergizes with FAS siRNA to induce apoptosis. Oncogene 2005, 24:5389-5395.
• [7]Kuhajda FP, Jenner K, Wood FD, Hennigar RA, Jacobs LB, Dick JD, Pasternack GR: Fatty acid synthesis: a potential selective target for antineoplastic therapy. Proc Natl Acad Sci U S A 1994, 91:6379-6383.
• [8]Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL: The 2005 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma. Am J Surg Pathol 2005, 29:1228-1242.
• [9]Swinnen JV, Roskams T, Joniau S, van Poppel H, Oyen R, Baert L, Heyns W, Verhoeven G: Overexpression of fatty acid synthase is an early and common event in the development of prostate cancer. Int J Cancer 2002, 98:19-22.
• [10]Migita T, Ruiz S, Fornari A, Fiorentino M, Priolo C, Zadra G, Inazuka F, Grisanzio C, Palescandolo E, Shin E, et al.: Fatty acid synthase: a metabolic enzyme and candidate oncogene in prostate cancer. J Natl Cancer Inst 2009, 101:519-532.
• [11]D’Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, Tomaszewski JE, Renshaw AA, Kaplan I, Beard CJ, Wein A: Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 1998, 280:969-974.
• [12]Epstein JI, Feng Z, Trock BJ, Pierorazio PM: Upgrading and downgrading of prostate cancer from biopsy to radical prostatectomy: incidence and predictive factors using the modified Gleason grading system and factoring in tertiary grades. Eur Urol 2012, 61:1019-1024.
• [13]Iremashvili V, Manoharan M, Pelaez L, Rosenberg DL, Soloway MS: Clinically significant Gleason sum upgrade: external validation and head-to-head comparison of the existing nomograms. Cancer 2012, 118:378-385.
• [14]Kuhajda FP, Pizer ES, Li JN, Mani NS, Frehywot GL, Townsend CA: Synthesis and antitumor activity of an inhibitor of fatty acid synthase. Proc Natl Acad Sci U S A 2000, 97:3450-3454.
• [15]Menendez JA, Lupu R: Oncogenic properties of the endogenous fatty acid metabolism: molecular pathology of fatty acid synthase in cancer cells. Curr Opin Clin Nutr Metab Care 2006, 9:346-357.
• [16]Swinnen JV, Brusselmans K, Verhoeven G: Increased lipogenesis in cancer cells: new players, novel targets. Curr Opin Clin Nutr Metab Care 2006, 9:358-365.
• [17]Epstein JI, Carmichael M, Partin AW: OA-519 (fatty acid synthase) as an independent predictor of pathologic state in adenocarcinoma of the prostate. Urology 1995, 45:81-86.
• [18]Pizer ES, Pflug BR, Bova GS, Han WF, Udan MS, Nelson JB: Increased fatty acid synthase as a therapeutic target in androgen-independent prostate cancer progression. Prostate 2001, 47:102-110.
• [19]Horiguchi A, Asano T, Ito K, Sumitomo M, Hayakawa M: Fatty acid synthase over expression is an indicator of tumor aggressiveness and poor prognosis in renal cell carcinoma. J Urol 2008, 180:1137-1140.
• [20]Thomas C, Pfirrmann K, Pieles F, Bogumil A, Gillitzer R, Wiesner C, Thuroff JW, Melchior SW: Predictors for clinically relevant Gleason score upgrade in patients undergoing radical prostatectomy. BJU Int 2012, 109:214-219.
• [21]Nguyen PL, Ma J, Chavarro JE, Freedman ML, Lis R, Fedele G, Fiore C, Qiu W, Fiorentino M, Finn S, et al.: Fatty acid synthase polymorphisms, tumor expression, body mass index, prostate cancer risk, and survival. J Clin Oncol 2010, 28:3958-3964.