Lin Anne, Weiser Martin R, Klimstra David S, Paty Philip B, Tang Laura H, Al-Ahmadie Hikmat, Hoo Park Sun, Guillem Jose G, Temple Larissa, Wong W Douglas, Gerald William L, Shia Jinru
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Hum Pathol. 2007 Jun;38(6):850-6. doi: 10.1016/j.humpath.2006.12.016. Epub 2007 Apr 18.
alpha-methylacyl-coenzyme A racemase (AMACR) is a recently discovered biomarker that is shown to be overexpressed in some prostatic carcinomas and associated with prostatic cancer progression. Given that AMACR plays an important role in peroxisomal beta-oxidation of branched-chain fatty acids from red meat and dairy products, and that consumption of red meat may increase risk of developing colon cancer as suggested by epidemiological studies, it is plausible to explore the function of AMACR in colorectal carcinoma. A few previous studies have indeed observed overexpression of AMACR in 45% to 69% of the colorectal carcinomas. However, the clinical and pathologic characteristics of such AMACR expressers have not been investigated. In this study, the immunohistochemical expression pattern of AMACR of 163 patients with primary colorectal carcinoma treated primarily with surgical resection was analyzed and correlated with tumor pathologic features (tumor location, histologic type, grade, pathologic stage, lymph node and distant metastasis) and patient outcome (disease-specific survival). The results showed variable positive staining for AMACR in 123 (75%) of 163 tumors, and moderate to strong staining in 63 (39%) of 163. Lack of staining or low-intensity staining appeared to correlate significantly with mucinous histology (P < .001), poor tumor differentiation (P = .021), and presence of lymphovascular invasion (P = .032). Patients whose tumors showed lack of staining or low-intensity staining also had a significantly worse 5-year disease-specific survival (P < .012), as did patients whose tumors had lymphovascular invasion, or were of high American Joint Committee on Cancer (AJCC) stage. On multivariate analysis, AMACR staining and AJCC staging remained independent predictors for patient outcome. Thus, our data suggest that AMACR expression in colorectal carcinoma correlates with certain tumor pathologic characteristics (histologic type, differentiation, and lymphovascular invasion) and patient outcome. Additional confirmatory studies are needed to establish the significance of AMACR as a prognostic marker for colorectal carcinoma. Further investigation on interaction between AMACR and other known colorectal cancer development pathways may provide new insights on colorectal carcinogenesis.
α-甲基酰基辅酶A消旋酶（AMACR）是一种最近发现的生物标志物，已证实在某些前列腺癌中过度表达，并与前列腺癌进展相关。鉴于AMACR在红肉和乳制品中支链脂肪酸的过氧化物酶体β-氧化中起重要作用，且流行病学研究表明食用红肉可能增加患结肠癌的风险，因此探索AMACR在结直肠癌中的功能是合理的。先前的一些研究确实观察到45%至69%的结直肠癌中AMACR过度表达。然而，此类AMACR表达者的临床和病理特征尚未得到研究。在本研究中，分析了163例主要接受手术切除治疗的原发性结直肠癌患者的AMACR免疫组化表达模式，并将其与肿瘤病理特征（肿瘤位置、组织学类型、分级、病理分期、淋巴结和远处转移）及患者预后（疾病特异性生存）相关联。结果显示，163个肿瘤中有123个（75%）AMACR呈不同程度的阳性染色，163个中有63个（39%）呈中度至强染色。无染色或低强度染色似乎与黏液性组织学显著相关（P <.001）、肿瘤分化差（P =.021）以及淋巴管浸润的存在（P =.032）。肿瘤显示无染色或低强度染色的患者5年疾病特异性生存率也显著较差（P <.012），肿瘤有淋巴管浸润或处于美国癌症联合委员会（AJCC）高分期的患者也是如此。多因素分析显示，AMACR染色和AJCC分期仍然是患者预后的独立预测因素。因此，我们的数据表明结直肠癌中AMACR表达与某些肿瘤病理特征（组织学类型、分化和淋巴管浸润）及患者预后相关。需要更多的验证性研究来确定AMACR作为结直肠癌预后标志物的意义。对AMACR与其他已知结直肠癌发生途径之间相互作用的进一步研究可能会为结直肠癌发生提供新的见解。
