Significance of overexpression of alpha methylacyl-coenzyme A racemase in hepatocellular carcinoma (original) (raw)
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Applied Immunohistochemistry Molecular Morphology Aimm Official Publication of the Society For Applied Immunohistochemistry, 2005
Alpha-methylacyl-coenzyme A racemase (AMACR; P504S) is a mitochondrial and peroxisomal enzyme involved in the metabolism of branched-chain fatty acid and bile acid intermediates. Recently, AMACR has been demonstrated to be overexpressed in localized and metastatic prostate cancer and in high-grade prostatic intraepithelial neoplasia but not in normal prostatic glands, suggesting that it may be an important tumor marker. This study examines AMACR expression in a variety of human cancers to assess its viability as a tumor marker in the clinical setting. Two hundred sixty-three cancers from different sites were examined in three multitumor tissue micro arrays, which included two or three tissue cores (1.0 mm in diameter) from each neoplastic and normal tissue specimen. Cancers studied included breast (94 cases), prostate (38), lung (28), endometrium (27), colon (29), ovary (26), and melanoma (21). Normal tissues in the microarray were prostate (15), lung (6), endometrium (5), colon (4), ovary (2), and skin (3). Sections were immunostained, after prior pressure cooker antigen retrieval, using rabbit monoclonal AMACR antibody (1:40) (Zeta Corp, Sierra Madre, CA) and horseradish peroxidase-labeled polymer conjugated secondary antibody (Envision, Dako, Carpinteria, CA). A section of prostate cancer and prostatic intraepithelial neoplasia was used as positive control. Protein expression was scored as negative, weak (faint cytoplasmic or granular apical staining), moderate (diffuse granular cytoplasmic stain), and strong (diffuse intense cytoplasmic stain). Only moderate and strong staining was considered as positive staining, based on prior work. AMACR protein overexpression was found in several cancers, including prostate (34/38 [89.5%]), colon (13/29 [44.8%]), lung (4/28 [14.3%]), melanoma (2/21 [9.5%]), endometrium (2/27 [7.4%]), and breast (3/94 [3.2%]). None of the ovarian cancers (26 cases) demonstrated AMACR overexpression. AMACR expression was not present in any of the normal tissues nor in benign prostatic tissue associated with prostate carcinomas. This study suggests that AMACR is potentially an important tumor marker, particularly for prostate and colon cancer. It may be a useful adjunct to an immunohistochemical panel employed in the differential diagnosis of colon versus ovarian and breast carcinoma; the latter two infrequently express AMACR.
Tumor Markers and Hepatocellular Carcinoma
Journal of Biology and Today's World, 2015
Hepatocellular carcinoma (HCC) cancer is a lethal cancer and early diagnosis of HCC is very important for improving the survival rate of patients. Measurement of Alfa-Fetoprotein (AFP) in combination with iconography and liver biopsy are commonly used in the diagnosis of liver cancer as well as HCC. Despite the wide use of AFP in HCC diagnosis and introducing this tumor marker as the gold standard biomarker for HCC detection, the specificity and sensitivity of AFP used in screening for HCC is very controversial. In recent years, along with development of molecular biology and extensive research about ethnology of cancers and simultaneously advances in technology, researchers identified new tumor markers in this disease. In the latest researches various biomarkers including embryonic antigen, protein antigens, cytokines, enzymes and isoenzymes and related genes for effective early diagnosis and monitoring of hepatocellular carcinoma are introduced. In this review, a summary of the data of various studies that discuss new tumor markers involved in hepatocellular carcinoma and classification of these biomarkers was investigated.
The American Journal of Pathology, 2002
␣-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 AM-ACR expression is not hormone-dependent but may in fact be a marker of tumor differentiation.
IP innovative publication pvt. ltd, 2019
P504S is a prostate cancer specific gene that encodes for α-methylacyl CoA racemase (AMACR). AMACR has been shown to be selectively over expressed in prostatic adenocarcinoma with minimal to undetectable expression in benign prostatic tissue. We studied the expression of AMACR in 30 cases of prostatic adenocarcinoma using polyclonal anti-AMACR antibody and correlated it with Gleason score. Extent of staining/proportion score (0: no positive cells; 1+:1-10% positive cells; 2+11-50% positive cells; 3+>50% positive cells) was also recorded and correlated with Gleason score. All the 30 cases showed strong, cytoplasmic granular AMACR staining irrespective of their Gleason score with 26 (86.7%) cases showing immunostaining in more than 50% tumor cells (3+ proportion score). Benign prostate tissue adjacent to adenocarcinoma showed negative AMACR staining. No correlation was seen between Gleason score and AMACR proportion score. We concluded that AMACR is a highly sensitive positive marker of prostatic adenocarcinoma.
Alpha-methyl CoA racemase expression in renal cell carcinomas
Human Pathology, 2006
Alpha-methyl CoA racemase (AMACR), a new molecular marker for prostate cancer, has been recently reported to be one of the most highly expressed genes in papillary renal cell carcinomas (RCCs). We tested the diagnostic usefulness of AMACR antibody in a series of 110 renal tumors: 53 papillary RCCs (33 type 1, 20 type 2); 25 conventional RCCs; 6 chromophobe RCCs; 9 oncocytomas; 5 mucinous tubular and spindle tumors; 2 urothelial carcinomas; 7 angiomyolipomas; and 2 Bellini carcinomas. Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue sections, with a primary prediluted rabbit monoclonal anti-AMACR antibody. Both type 1 and type 2 papillary RCCs exhibited cytoplasmic immunoreactivity for AMACR, with diffuse strong granular staining in 96.4% (53/55) of tumors, without correlation with type or nuclear grade. The 5 mucinous, tubular, and spindle cell carcinomas strongly expressed AMACR, and only 5 of 25 clear cell RCCs and 1 of 9 oncocytomas were focally reactive. The remaining 6 chromophobe RCCs, 5 urothelial carcinomas, and Bellini duct carcinomas showed no immunoreactivity for AMACR. Because high expression of AMACR is found in papillary RCCs (type 1 and 2) and in mucinous, tubular, and spindle cell carcinomas of the kidney, immunostaining for AMACR should be used in conjunction with other markers when histological typing of a renal tumor is difficult. D
Expression of AMACR (α-Methylacyl CoA racemase) in Prostatic Lesion.
IOSR Journals , 2019
Prostate cancer is the second most common cause of cancer and the sixth leading cause of cancer death among men worldwide, To diagnose prostate cancer, no specific single histologic feature is sufficiently available. It is a challenging task to accurately diagnose small foci of prostate cancer for pathologists and to distinguish cancer from its benign mimickers. Establishing a definitive diagnosis of malignancy in prostate needle biopsies with very little foci of adenocarcinoma is a major diagnostic challenge for pathologists. A positive diagnostic marker specific for prostatic adenocarcinoma may enhance the ability to detect limited prostate cancer and reduce errors in diagnosis. The recent discovery of the overexpression of P504S/α-Methylacyl coenzyme A racemase (AMACR) in prostate cancer is a successful example of translating an advanced molecular finding into clinical practice. AMACR (P504S) has been proven to be one of the few biomarkers that can help distinguish cancer from benign cells, with high sensitivity and specificity for prostate carcinoma. This study focuses on the study of AMACR (P504S) expression in prostate cancer, premalignant lesions, benign prostate tissues, and other normal and malignant tissues and a discussion of its clinical usefulness. We recommend the interpretation of the AMACR immunohistochemical results in routine surgical pathology practice and also discuss the potential future applications of this marker in diagnosis of various lesions
Human Pathology, 2013
The expression of alpha-methylacyl-coenzyme-A-racemase (AMACR) has previously been reported in 75 to 100% of urethral/bladder clear cell carcinomas, tumors that are known to display broad phenotypic overlap with their identically-named müllerian counterparts. Herein, we assess the utility of AMACR in distinguishing endometrial clear cell carcinomas (CCC) from endometrial serous carcinomas (ESC) and endometrial endometrioid carcinomas (EEC). 111 endometrial carcinomas in a tissue microarray, including 49 CCC, 13 ESC and 49 EEC, were assessed for AMACR immunoreactivity, with results scored semi-quantitatively (scores 0, 1+, 2+, 3+ for 0%, 1-5%, 6-50%, >50% immunoreactive cells respectively). 50 (45%) of the 111 carcinomas were AMACR-positive, with the following score distribution: CCC: 0 (n=12), 1+ (n=12), 2+ (n=3), 3+ (n=22); EEC: 0 (n=38), 1+ (n=4), 2+ (n=4), 3+ (n=3); ESC: 0 (n=11), 1+ (n=1), 2+ (n=0), 3+ (n=1). AMACR expression was significantly more frequent in CCC (75%) than in ESC (15%) or EEC (22%), p<0.0001. The sensitivity and specificity of AMACR expression in classifying a carcinoma as CCC were 0.75 (95% CI: 0.61-0.86) and 0.79 (95% CI: 0.66-0.88) respectively, with an odds ratio of 11.62 (95% CI: 5-28, p < 0.001), and an area under the curve of 0.79 (95% CI: 0.68 to 0.88). These findings indicate that AMACR expression is strongly associated with CCC and displays a relatively robust diagnostic test performance. However, its practical utility may be limited by the focal nature of its expression in 32% of the AMACR-positive CCC cases, as well as its expression in 15-22% of the non-CCC histotypes.
Diagnostic biomarkers in hepatocellular carcinoma
Pure and Applied Biology, 2020
Being the second most lethal type of cancer, Hepatocellular carcinoma (HCC) annually kills 650,000 individuals worldwide, approximately, prompting communal malignant tumor that accounts for more than 90% of liver cancer. We aimed to clarify the functioning of different diagnostic markers of incidence and progression of hepatocellular carcinoma. Biomarkers are molecular indicators that are very imperative for the management of different diseases. Different biomarkers of HCC, such as serum and tumor biomarkers have been diagnosed and their presence in urine, tissues and serum indicates the development of the tumor. The diagnoses at early stages helps in the prevention of HCC. In the case of HCC, more than 70% of patients showed an increased level of alpha-fetoprotein (AFP) due to excretion of the tumor and thus the level of AFP in the body is one of the most important biomarkers of HCC. Another important biomarker is AFP-L3 is considered as more precise in the diagnosis of HCC than AFP. Percentages of AFP-L3 are measured with high sensitivity and hence known as the most important early predictor at low AFP levels. One of the significant biomarkers is DCP (Des-gamma-carboxy-prothrombin) that is relatively more accurate than the other two diagnostic pointers. While differentiating malignant HCC with non-malignant liver disease, it was clear that the diagnostic value of DCP is better than AFP. DCP is a great deal more effective than AFP in diagnosing HCC on the comparatively lower level. When compared these diagnostic carcinoma biomarkers, showed the potency in a descending order from DCP>AFP> AFP-L3.
Histopathology, 2007
Aims: a-Methylacyl-CoA racemase (AMACR) is a sensitive and specific immunohistochemical marker of prostatic malignancy, staining 80-100% of prostatic cancers with absent staining in benign glands. However, positive staining in benign conditions as well as low rates of AMACR reactivity in prostatic cancer variants have been described. Preliminary use of AMACR immunohistochemistry in our institution has suggested lower specificity and sensitivity for prostatic cancer than initially proposed. The aim of this study was to establish true rates of AMACR reactivity in prostatic cancer and benign prostatic hyperplasia (BPH). Methods and results: AMACR immunohistochemistry was performed on sections from 57 prostatic cancers and 44 BPH resections. Ninety-one percent of cancers were AMACR+, with diffuse (> 75%) tumour staining in 53% of cases. Thirty-eight percent of tumours showed heterogeneous expression (1-75% tumour staining). This was significantly correlated with increased Gleason score. High-grade prostatic intraepithelial neoplasia (PIN) was AMACR+ in 87% of cancers. Eleven percent of BPH showed moderate or strong staining in benign glands, focally mimicking the malignant staining pattern. Conclusions: This study confirms heterogeneous AMACR expression in prostatic cancer and shows a correlation with Gleason score. Positive staining in BPH is also documented, thus emphasizing the importance of interpreting AMACR immunohistochemistry in the context of other findings in a diagnostic setting.
Prognostic value of alpha-methyl CoA racemase (AMACR) expression in renal cell carcinoma
World Journal of Urology, 2011
Purpose Alpha-methyl CoA racemase (AMACR) is used as an immunohistochemical marker for renal cell carcinoma (RCC) subtyping to distinguish papillary (pap) RCC. Expression of AMACR in other renal tumor subtypes is inhomogeneous, and the clinical and prognostic value of AMACR is unknown. The aim of this study was to asses AMACR protein expression in different RCC subtypes and to investigate its prognostic significance. Methods Protein expression of AMACR was analyzed in 1,088 renal tumor samples, among them 809 clear cell RCC and 151 papRCC, by immunohistochemistry using tissue microarry (TMA) technique. Results were correlated with clinicopathological data and to follow-up data [overall (OS)/cancer-specific survival (CSS)]. Results Frequency of AMACR expression was significantly higher in papRCC compared to other tumor subtypes (83% vs. 15-35%, p \ 0.0001). Presence of AMACR did not correlate with stage or nodal metastases in papRCC. In a dichotomized scoring (negative vs. positive expression), an inverse correlation between higher grade (p = 0.03) and presence of distant metastasis (p = 0.014) was observed in papRCC. AMACR expression correlated with the presence of nodal metastasis in ccRCC (p = 0.02). Both in ccRCC and in papRCC, OS and CSS did not correlate with the AMACR expression status. Conclusions The high expression in papRCC confirms AMACR to be a marker for subtype differentiation in RCC, while a missing expression in this subtype seems to be associated with negative pathological features. However, in contrast to other tumor entities, AMACR expression seems to have a limited prognostic impact in renal carcinoma, especially with regard to survival.