Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Prostate. 2012 Aug 1;72(11):1159-70. doi: 10.1002/pros.22465. Epub 2011 Nov 29.
Field cancerization denotes the occurrence of molecular alterations in histologically normal tissues adjacent to tumors. In prostate cancer, identification of field cancerization has several potential clinical applications. However, prostate field cancerization remains ill defined. Our previous work has shown up-regulated mRNA of the transcription factor early growth response 1 (EGR-1) and the lipogenic enzyme fatty acid synthase (FAS) in tissues adjacent to prostate cancer.
Immunofluorescence data were analyzed quantitatively by spectral imaging and linear unmixing to determine the protein expression levels of EGR-1 and FAS in human cancerous, histologically normal adjacent, and disease-free prostate tissues.
EGR-1 expression was elevated in both structurally intact tumor adjacent (1.6× on average) and in tumor (3.0× on average) tissues compared to disease-free tissues. In addition, the ratio of cytoplasmic versus nuclear EGR-1 expression was elevated in both tumor adjacent and tumor tissues. Similarly, FAS expression was elevated in both tumor adjacent (2.7× on average) and in tumor (2.5× on average) compared to disease-free tissues.
EGR-1 and FAS expression is similarly deregulated in tumor and structurally intact adjacent prostate tissues and defines field cancerization. In cases with high suspicion of prostate cancer but negative biopsy, identification of field cancerization could help clinicians target areas for repeat biopsy. Field cancerization at surgical margins on prostatectomy specimen should also be looked at as a predictor of cancer recurrence. EGR-1 and FAS could also serve as molecular targets for chemoprevention.
田间癌变表示肿瘤相邻组织中发生分子改变。在前列腺癌中,鉴定田间癌变具有几个潜在的临床应用。然而,前列腺田间癌变仍然定义不清。我们以前的工作表明,转录因子早期生长反应 1 (EGR-1) 和生脂酶脂肪酸合酶 (FAS) 的 mRNA 在癌旁组织中上调。
通过光谱成像和线性解混定量分析免疫荧光数据,以确定人癌旁、组织学正常相邻和无疾病前列腺组织中 EGR-1 和 FAS 的蛋白表达水平。
与无疾病组织相比,结构完整的肿瘤旁组织(平均升高 1.6 倍)和肿瘤组织(平均升高 3.0 倍)中 EGR-1 的表达均升高。此外,肿瘤旁和肿瘤组织中细胞质与核 EGR-1 表达的比值均升高。同样,与无疾病组织相比,肿瘤旁组织(平均升高 2.7 倍)和肿瘤组织(平均升高 2.5 倍)中 FAS 的表达均升高。
在肿瘤和结构完整的相邻前列腺组织中,EGR-1 和 FAS 的表达同样失调,定义了田间癌变。在怀疑前列腺癌但活检阴性的情况下,鉴定田间癌变可以帮助临床医生确定重复活检的部位。前列腺切除术标本手术切缘的田间癌变也应作为癌症复发的预测指标。EGR-1 和 FAS 也可作为化学预防的分子靶点。