Schlomm Thorsten, Kirstein Patrick, Iwers Liv, Daniel Birte, Steuber Thomas, Walz Jochen, Chun Felix H K, Haese Alexander, Kollermann Jens, Graefen Markus, Huland Hartwig, Sauter Guido, Simon Ronald, Erbersdobler Andreas
Martini-Clinic, Prostate Cancer Center, Department of Pathology and Urology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, Germany.
Clin Cancer Res. 2007 Nov 15;13(22 Pt 1):6579-84. doi: 10.1158/1078-0432.CCR-07-1257.
The epidermal growth factor receptor (EGFR) is a protein involved in the tumor progression of many cancer types and is an important therapeutic target. To determine its role in prostate cancer, we analyzed 2,497 prostate cancers on the DNA and protein level.
Tissue samples from each tumor were brought into a tissue microarray and analyzed by immunohistochemistry and fluorescence in situ hybridization. A subset of cancers was also sequenced for EGFR exon 18 to 21 mutations.
Detectable EGFR expression was found in 18% of cancers and was significantly associated with high grade, advanced stage, and high risk for prostate-specific antigen recurrence in univariate analysis (P < 0.0001, each). Fluorescence in situ hybridization analysis with a dual-labeling probe for centromere 7 and EGFR showed increased EGFR copy number in 3.3% of cases. EGFR copy number gains were mostly due to an overrepresentation of the entire chromosome and were associated with EGFR protein expression (P < 0.0001), high grade (P < 0.0001), and advanced stage (P = 0.0056). Only one cancer had a high-level amplification (>20 EGFR gene copies per cell). This amplification was heterogeneous, involving only approximately 30% of the cancer volume. EGFR mutations were not found in 35 of the cases analyzed.
Increased EGFR expression is often seen in prostate cancer and is associated with poor prognosis. The significant association of EGFR copy number gains with protein expression argues for the significant role of minimal gene copy number changes for protein expression. Although EGFR expression was not an independent prognostic variable, the potential utility of anti-EGFR medications might be worth further investigation in EGFR-expressing prostate cancer.
表皮生长因子受体（EGFR）是一种参与多种癌症类型肿瘤进展的蛋白质，是一个重要的治疗靶点。为确定其在前列腺癌中的作用，我们在DNA和蛋白质水平分析了2497例前列腺癌。
将每个肿瘤的组织样本制成组织微阵列，通过免疫组织化学和荧光原位杂交进行分析。还对一部分癌症进行了EGFR外显子18至21突变的测序。
在18%的癌症中发现可检测到的EGFR表达，在单变量分析中，其与高分级、晚期以及前列腺特异性抗原复发的高风险显著相关（每项P<0.0001）。使用针对7号染色体着丝粒和EGFR的双标记探针进行的荧光原位杂交分析显示，3.3%的病例中EGFR拷贝数增加。EGFR拷贝数增加主要是由于整条染色体的过度表达，并且与EGFR蛋白表达（P<0.0001）、高分级（P<0.0001）和晚期（P=0.0056）相关。只有一例癌症具有高水平扩增（每个细胞>20个EGFR基因拷贝）。这种扩增是异质性的，仅涉及约30%的癌体积。在所分析的35例病例中未发现EGFR突变。
前列腺癌中常可见EGFR表达增加，且与预后不良相关。EGFR拷贝数增加与蛋白表达的显著相关性表明最小基因拷贝数变化对蛋白表达具有重要作用。虽然EGFR表达不是一个独立的预后变量，但抗EGFR药物在表达EGFR的前列腺癌中的潜在效用可能值得进一步研究。
