AMACR/P504S在胃黏膜高度异型增生诊断中的价值

目的观察AMACR/P504S在正常胃黏膜、不确定性异型增生、低度异型增生、高度异型增生和胃肠型腺癌中的表达,探讨其在胃黏膜高度异型增生诊断中的价值。方法应用免疫组化EnVision法检测20例无异型增生、30例不确定性异型增生、25例低度异型增生、30例高度异型增生和20例肠型腺癌中AMACR/P504S的表达。结果 AMACR/P504S在无异型增生和不确定性异型增生的胃黏膜中均为阴性表达,在低度异型增生中AMACR/P504S阳性率为4.0%,高度异型增生和肠型腺癌中阳性率分别为73.3%和55%,AMACR/P504S在高度异型增生中的表达明显高于低度异型增生(P<0.01),与肠型腺癌无差异(P>0.05)。AMACR/P504S对高度异型增生诊断的特异性为98.7%,敏感性为73.3%。结论 AMACR/P504S可作为胃黏膜高度异型增生与低度异型增生和不确定性异型增生鉴别诊断的免疫标记物。     

Alpha-methylacyl-CoA racemase (AMACR/P504S) protein expression in urothelial carcinoma of the upper urinary tract correlates with tumour progression

Alpha-methylacyl-CoA racemase (AMACR/P504S) is a useful biomarker of prostate cancer. We evaluated the expression of AMACR in upper urinary tract urothelial carcinomas with respect to associations with tumour stage, grade and metastasis-free survival. A total of 268 tumours were investigated immunohistochemically using a tissue microarray technique. AMACR expression was noted in 127 of 261 (48.7%) evaluated tumours and was associated with high tumour stage [58 of 139 (41.7%) pTa/pT1 vs. 69 of 122 (56.6%) pT2–pT4, P=0.019] and high tumour grade [44 of 137 (32.1%) low vs. 83 of 124 (66.9%) high grade, P<0.001]. In addition, AMACR expression was associated with the presence of tumour necrosis (P<0.001) and marked stromal desmoplasia (P=0.0026). This correlation indicates that increased AMACR expression might be related to hypoxia-induced changes in cancer cell metabolism, such as increased dependence on fatty acid oxidation for energy generation. Progressive disease was observed in 73 of 183 (39.9%) patients with solitary invasive carcinomas and was associated with AMACR expression (P=0.017). Multivariate analysis, however, proved only pT-stage >1 (P<0.001) and high tumour grade (P<0.001) to be independent predictors of patient outcome. In conclusion, AMACR expression correlated with advanced tumour stage and grade and may serve as an additional prognostic indicator in upper urinary tract urothelial cancer.     

Renal papillary adenoma--a putative precursor of papillary renal cell carcinoma

The precursor lesions of renal cell carcinoma (RCC) are unknown. The purpose of this study is to determine the incidence, histomorphological features, and immunohistochemical features of papillary adenoma and elucidate its potential relationship to RCC. We reviewed 542 consecutive nephrectomy specimens over an 8-year period. Immunohistochemistry was carried out with antibodies specific for alpha-methyl-coenzyme A racemase (AMACR) and glutathione S-transferase alpha (clear-cell RCC marker). Thirty-eight (7%) nephrectomy specimens showed histologic evidence of papillary adenoma. Of these 38 cases, 18 (47%) arose in the setting of papillary RCC (PRCC). Seven papillary adenomas (18%) occurred in the setting of acquired polycystic kidney disease (APKD), 6 in clear-cell RCCs, 3 in chromophobe RCCs, 2 in end-stage kidney disease, 1 in oncocytoma, 1 in angiomyolipoma, and 1 in renal schwannoma. Furthermore, papillary adenomas were more commonly found in kidneys removed for PRCC (25%, 18/71) than in kidneys harboring clear-cell RCC (1.9%, 6/318). Histomorphologically, papillary adenomas were characterized by varying proportions of papillae and tubules formed by cuboidal cells with scant basophilic cytoplasm similar to those in type 1 PRCC. Adenomas associated with PRCC tend to be multiple in number (61% [11/18] of cases had >2 adenomas; mean, 5). In contrast, 100% of papillary adenomas arising in other conditions had less than 2 adenomas. Most of the adenomas (82%, 31/38) stained strongly for AMACR in a fashion similar to that of PRCC. The 7 AMACR-negative cases all arose in the setting of APKD. In this study of surgical specimens, the high coincidence, multifocality, and histologic and immunohistochemical similarities between papillary adenoma and PRCC suggest that the 2 are strongly associated and may represent a continuum of 1 biologic process. In contrast, adenomas associated with APKD exhibit distinct morphological and immunohistochemical features and, therefore, may have an entirely different pathogenesis.     

Oncocytic renal cell carcinoma having papillotubular growth: rare morphological variant of papillary renal cell carcinoma

Herein is described a unique renal cell tumor with previously unreported morphological and immunohistochemical features. The patient was a 78-year-old Japanese man. A huge left renal tumor was found on ultrasound during evaluation of left abdominal distention. The tumor was macroscopically characterized by a non-infiltrative border, pale yellow to grayish color, foci of hemorrhage and partial edematous change. Histologically the tumor had an extensive small tubular growth pattern often with papillary fronds mainly composed of oncocytic cells with deeply eosinophilic granular cytoplasm. Clear vacuolated cells were scattered among the oncocytic cells. The present case had an unusual immunohistochemical profile for all known types of renal cell tumors, but both the oncocytic cells and the clear vacuolated cells were strongly immunoreactive for α-methylacyl-coenzyme A racemase. It is concluded that the tumor may be a candidate for a rare variant of papillary renal cell carcinoma. Further cases having similar features are awaited for a definitive classification of this tumor as a previously undescribed tumor type.     

Alpha-methylacyl-CoA racemase expression is upregulated in gastric adenocarcinoma: a study of 249 cases

Alpha-methylacyl-CoA racemase (AMACR [P504S]) is a mitochondrial and peroxisomal enzyme involved in beta-oxidation of dietary branched-chain fatty acids and their derivatives. Recent studies showed that AMACR is expressed in several neoplasms, including prostate and colon cancer. However, AMACR expression in gastric neoplasms has yet to be thoroughly investigated. Because AMACR overexpression in human solid tumors is a potential target for cancer treatment, we aimed to evaluate the expression of AMACR in a large cohort of patients with gastric adenocarcinoma. The study evaluated 249 primary gastric adenocarcinomas by immunohistochemistry. Nonneoplastic gastric tissue samples from various sites (antrum, body, fundus, and pylorus) were also examined. The immunopositivity of each sample was graded on a scale from 0 to 3 (0, no expression; 1, weak expression, 2, intermediate expression; 3, strong expression). We observed AMACR expression in 141 tumor cases: 44, 47, and 50 cases had weak, intermediate, and strong expression, respectively. Both intestinal and signet ring cell adenocarcinoma cases had overexpression of AMACR, however intestinal adenocarcinoma had significantly higher expression than did signet ring cell adenocarcinoma (p<0.05). Nonneoplastic gastric mucosa did not show AMACR expression. The results of our study demonstrate that AMACR expression is upregulated in gastric cancer, and suggest that further prospective studies to explore the potential role of AMACR as a therapeutic target for gastric cancer are warranted.     

AMACR联合P63或CK34βE12在前列腺癌诊断和鉴别诊断中的应用

目的评价AMACR联合P63或CK34βE12在前列腺癌(PC)诊断和鉴别诊断中的应用价值。方法应用免疫组化SP法检测了73例前列腺病变标本[前列腺癌、良性前列腺增生(BPH)、高级别前列腺上皮内瘤(HGPIN)、低级别前列腺上皮内瘤(LGPIN)和非典型腺瘤样增生(AAH)]中AMACR、P63和CK34βE12的表达情况。结果①AMACR在PC中阳性率为96.43%(27/28),在HGPIN、LGPIN、AAH和BPH中阳性率分别为83.33%(10/12)、11.11%(1/9)、16.67%(1/6)和0。癌组化明显高于LGPIN、AAH和BPH(P<0.001),与HGPIN之间无差异(P=0.209);②P63和CK34βE12在BPH、LGPIN和AAH中全部为阳性染色,而在PC中全部为阴性。P63和CK34βE12在HGPIN中的阳性率分别为83.33%(10/12)和91.67%(11/12)。癌组化低于HGPIN等其他病变(P<0.001);③AMACR阳性协同P63或CK34βE12阴性两种标记在PC中表达率为96.4%,HGPIN为8.33%,LGPIN、AAH和BPH为0。癌组化明显高于HGPIN等其他病变(P<0001)。结论AMACR是PC较高的敏感特异性瘤标,AMACR联合P63或CK34βE12的检测对PC的诊断和鉴别诊断有较好的应用价值。     

Paneth cell-like change in benign prostate can account for P504S (AMACR) reactivity

Paneth cell-like neuroendocrine metaplasia of benign and cancerous prostate was described in 1992. Here, we note that P504S (AMACR), the cytoplasmic marker for prostate cancer used alone or in concert with basal cell markers, can be strongly reactive in benign prostatic acini with Paneth cell-like change.     

P504S/AMACR在前列腺癌患者血清中的表达及其意义

目的:研究血清P504S/AMACR在前列腺癌筛查和早期诊断中的价值.方法:应用酶联免疫吸附试验(ELISA法),测定30例未经治疗的前列腺癌和20例未经治疗的前列腺增生患者血清P504S/AMACR水平.结果:(1) 前列腺癌组血清P504S/AMACR质量浓度[(4.12±0.24)ng·m1-1]明显高于前列腺增生组[(1.52±0.47)ng·m1-1],差异具有统计学意义(P<0.01).(2) 前列腺癌患者血清P504S/AMACR质量浓度与Gleason评分无关(P>0.05).(3) 前列腺癌患者血清P504S/AMACR质量浓度与PSA质量浓度无关(P=0.392).结论:初步证实检测P504S/AMACR在前列腺癌患者血清中的水平,可辅助PSA应用于前列腺癌的筛查,提高前列腺癌的早期诊断率.P504S/AMACR有望成为有效的前列腺癌瘤标之一.