α-Methylacyl-CoA Racemase (AMACR/P504S) Can Distinguish Hepatocellular Carcinoma and Dysplastic Hepatocytes From Benign Nondysplastic Hepatocytes

Guzman, Grace; Wu, Shoujin; Kajdacsy-Balla, André; Cotler, Scott J.

doi:10.1097/01.pai.0000208906.66618.61

Cited by 18 publications

(14 citation statements)

References 21 publications

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“…A staining index for each tissue core was obtained based on published methods [55]. The immuno-histochemical staining intensity of the nuclei or cytoplasm was assessed using a three tier grading system (weak or no staining = 0, moderate staining = 1, strong staining = 2) and the extent of stained nuclear positive cells (0-50%=1, 50-100%=2).…”

Section: Methodsmentioning

confidence: 99%

NFkB is essential for activin-induced colorectal cancer migration via upregulation of PI3K-MDM2 pathway

Jana

Krett

Guzman³

et al. 2017

Oncotarget

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Colorectal cancer (CRC) remains a common and deadly cancer due to metastatic disease. Activin and TGFB (TGFβ) signaling are growth suppressive pathways that exert non-canonical pro-metastatic effects late in CRC carcinogenesis. We have recently shown that activin downregulates p21 via ubiquitination and degradation associated with enhanced cellular migration independent of SMADs. To investigate the mechanism of metastatic activin signaling, we examined activated NFkB signaling and activin ligand expression in CRC patient samples and found a strong correlation. We hypothesize that activation of the E3 ubiquitin ligase MDM2 by NFkB leads to p21 degradation in response to activin treatment. To dissect the link between activin and pro-carcinogenic NFkB signaling and downstream targets, we found that activin but not TGFB induced activation of NFkB leading to increased MDM2 ubiquitin ligase via PI3K. Further, overexpression of wild type p65 NFkB increased MDM2 expression while the NFkB inhibitors NEMO-binding domain (NBD) and Bay11-7082 blocked the activin-induced increase in MDM2. In conclusion, in colon cancer cell migration, activin utilizes NFkB to induce MDM2 activity leading to the degradation of p21 in a PI3K dependent mechanism. This provides new mechanistic knowledge linking activin and NFkB signaling in advanced colon cancer which is applicable to targeted therapeutic interventions.

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Section: Methodsmentioning

confidence: 99%

NFkB is essential for activin-induced colorectal cancer migration via upregulation of PI3K-MDM2 pathway

Jana

Krett

Guzman³

et al. 2017

Oncotarget

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“…There are also some reports regarding the correlations between the expression of AMACR and the diagnostic potential for HCC. Guzman et al 9 have reported that AMACR could distinguish the HCC and the dysplastic hepatocytes from the benign nondysplastic hepatocytes based on the different staining patterns, but the sensitivity was not mentioned in this report; Li et al 10 have reported that AMACR could serve as a useful marker for distinguishing the well-differentiated HCC from the hepatocellular adenoma, and the AMACR might play a role in HCC development and progression. However, there has been conflicting reports in other studies where it was found that AMACR may not be a suitable marker; Willemoe et al 11 have reported that the staining patterns and staining intensities of AMACR in HCC tumour cells were not significantly different from the surrounding none tumour cells, and the AMACR staining could not distinguish the neoplastic from non-neoplastic liver cells.…”

Section: Introductionmentioning

confidence: 68%

α-Methylacyl-CoA racemase (AMACR) serves as a prognostic biomarker for the early recurrence/metastasis of HCC

Cai

Zeng

et al. 2014

J Clin Pathol

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AimsHepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and it is still lacking effective prognostic biomarkers so far. Previous results of the iTRAQ-based quantitative proteomics study (iTRAQ-2DLC-MS/MS) have shown that α-methylacyl-CoA racemase (AMACR) might be a promising prognostic biomarker for the early recurrence/metastasis of hepatocellular carcinoma (HCC). Here a large-scale cohort clinical study was performed to evaluate its prognostic potential.MethodsHCC samples from patients (n=158) were used for the construction of tissue microarray. The expression level of AMACR was determined by immunohistochemical staining. A large-scale cohort clinical study between the expression of AMACR and some major clinical parameter has been performed to assess the prognostic potential of AMACR for the early recurrence/metastasis of HCC.ResultsSome important clinical parameters such as α-fetoprotein, tumour numbers, dissemination to regional lymph nodes, tumour capsule and portal vein tumour thrombosis are significantly associated with the low expression of AMACR. The expression of AMACR was an independent factor for the survival of patients with HCC. The median survival time was 17 months in the low-expression group compared with 45 months in the high-expression group.ConclusionsThis study reveals that the AMACR might be a potential prognostic marker for predicting early recurrence/metastasis of HCC after hepatectomy.

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“…24,27,32,33 AMACR im mu nos ta i ning dis tin gu is hed nondy splas tic be nign he pa tocy tes from dysplas tic and malig nant he pa tocy tes, and high gra de dyspla si a from re ac ti ve aty pi a in Bar ret esop ha gus. 34,35 In the pre sent study, nor mal urot he li um did not show po si tive sta i ning with AMACR as in the pre vi o us stu di es. In the study of Went et al, 20 nor mal urot he li um was not sta i ned with AMACR, but AMACR expres si on was fo und in 15% of 41 in va si ve UC and 11% of 44 non-in va si ve UC.…”

Section: Discussionmentioning

confidence: 99%

Alpha-Methylacyl-CoA Racemase Expression in Invasive and Non-Invasive Bladder Urothelial Carcinomas

Çulhacı¹,

Çetin²,

Dündar³

2011

Turkiye Klinikleri J Med Sci

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A AB BS S T TR RA AC CT T OOb b j je ec c t ti i v ve e: : α-meth ylacyl-Co A ra ce ma se (AMACR) is a use ful di ag nos tic mar ker for pros ta tic ade no car ci no ma with a high sen si ti vity and spe ci fi city. Alt ho ugh ori gi nally vi e wed as a mar ker pre fe ren ti ally ex pres sed in pros ta tic car ci no ma, furt her stu di es sho wed its ex pres si on in ot her tu mors. The aim of this study is to exp lo re the pat ho lo gic sig ni fi can ce of AMACR ex pres si on in non-in va si ve and in va si ve urot he li al car ci no mas (UCs) of the blad der. M Ma a t te e r ri i a al l a an nd d M Me et t h ho od ds s: : A to tal of 160 UCs of the blad der and 77 ad ja cent tis su es with car ci no ma in si tu we re in ves ti ga ted for AMACR ex pres si on im mu no his toc he mi cally. Po si ti ve AMACR ex pres si on was de fi ned as cytop las mic sta i ning with granu lar pat tern. Sta i ning in ten sity was gra ded as 0 (ne ga ti ve), 1+ (we ak), 2+ (mo de ra te), or 3+ (strong). Po si ti vity was furt her clas si fi ed as fo cal or dif fu se. R Re e s su ul lt ts s: : Non-ne op las tic urot he li um re ve a led no ex pres si on of AMACR. The re was a sta tis ti cally sig ni fi cant po si ti ve cor re la ti on bet we en AMACR expres si on and gra de (p = 0.021). AMACR ex pres si on was sig ni fi cantly hig her in high-gra de UCs than low-gra de ones. AMACR ex pres si on was al so cor re la ted with the sta ge which was sig ni fi cantly higher in in va si ve tu mors (p < 0.001). Although non sig ni fi cant, dif fu se sta i ning was pro mi nent in high gra de tu mors. C Co on nc c l lu u s si i o on n: : In the pre sent study, AMACR was fo und to be ex pres sed in a sig ni fi cant num ber of urot he li al car ci no mas of the blad der. AMACR ex pres si on was shown to be cor re la ted with ad van ced tu mor gra de and sta ge. Our da ta sug gest that AMACR ex pres si on may be used as an ad di tio nal prog nos tic in di ca tor in urot he li al car ci no mas. Eva lu a ti on of AMACR ex pres si on may al so be useful in de ter mi ning the ag gres si ve ca pa city of the se tu mors in tran su ret hral re sec ti on spe ci mens.K Ke ey y W Wo or rd ds s: : Uri nary blad der ne op lasms; car ci no ma, tran si ti o nal cell; alp ha-meth ylacyl-co a ra ce ma se Ö ÖZ ZE ET T A Am ma aç ç: : α al fa me ta la sil Co A ra se maz (AMACR) pros ta te ade no kar si no mu için yük sek sen si tivi te ve spe si fi si te ye sa hip ya rar lı bir ta nı sal be lir le yi ci dir. İlk baş lar da baş lı ca pros tat kar si no ma la rın -da eks pre se edi len bir be lir le yi ci ola rak gö rül müş se de, son ra ki ça lış ma lar di ğer tü mör ler de eks pres yo nu nu gös ter miş tir. Bu ça lış ma nın ama cı AMACR eks pres yo nu nun non in va ziv ve in va ziv me sa ne kan ser le rin de pa to lo jik öne mi ni araş tır mak tır. G Ge e r re eç ç v ve e Y Yö ön n t te em m l le er r: : Yüz altmış me sa ne kanse ri ve 77 adet kom şu lu ğun da kar si no ma in si tu bu lu nan do ku lar da im mü no his to kim ya sal ola rak AMACR eks pres yo nu ara...

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α-Methylacyl-CoA Racemase (AMACR/P504S) Can Distinguish Hepatocellular Carcinoma and Dysplastic Hepatocytes From Benign Nondysplastic Hepatocytes

Cited by 18 publications

References 21 publications

NFkB is essential for activin-induced colorectal cancer migration via upregulation of PI3K-MDM2 pathway

NFkB is essential for activin-induced colorectal cancer migration via upregulation of PI3K-MDM2 pathway

α-Methylacyl-CoA racemase (AMACR) serves as a prognostic biomarker for the early recurrence/metastasis of HCC

Alpha-Methylacyl-CoA Racemase Expression in Invasive and Non-Invasive Bladder Urothelial Carcinomas

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