Department of Medical Oncology, Cancer Center, The State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
PLoS One. 2013 Apr 24;8(4):e62175. doi: 10.1371/journal.pone.0062175. Print 2013.
Penile Squamous Cell Carcinoma (SCC) is a rare cancer with poor prognosis and limited response to conventional chemotherapy. The genetic and epigenetic alterations of Epidermal Growth Factor Receptor (EGFR)-RAS-RAF signaling in penile SCC are unclear. This study aims to investigate four key members of this pathway in penile SCC. We examined the expression of EGFR and RAS-association domain family 1 A (RASSF1A) as well as the mutation status of K-RAS and BRAF in 150 cases of penile SCC. EGFR and RASSF1A expression was evaluated by immunohistochemistry. KRAS mutations at codons 12 and 13, and the BRAF mutation at codon 600 were analyzed on DNA isolated from formalin fixed paraffin embedded tissues by direct genomic sequencing. EGFR expression was positive in all specimens, and its over-expression rate was 92%. RASSF1A expression rate was only 3.42%. Significant correlation was not found between the expression of EGFR or RASSF1A and tumor grade, pT stage or lymph node metastases. The detection of KRAS and BRAF mutations analysis was performed in 94 and 83 tumor tissues, respectively. We found KRAS mutation in only one sample and found no BRAF V600E point mutation. In summary, we found over-expression of EGFR in the majority cases of penile SCC, but only rare expression of RASSF1A, rare KRAS mutation, and no BRAF mutation in penile SCC. These data suggest that anti-EGFR agents may be potentially considered as therapeutic options in penile SCC.
阴茎鳞状细胞癌（SCC）是一种罕见的癌症，预后差，对常规化疗反应有限。阴茎 SCC 中表皮生长因子受体（EGFR）-RAS-RAF 信号的遗传和表观遗传改变尚不清楚。本研究旨在研究该途径的四个关键成员在阴茎 SCC 中的作用。我们检测了 150 例阴茎 SCC 组织中 EGFR 和 RAS 关联结构域家族 1A（RASSF1A）的表达以及 K-RAS 和 BRAF 突变状态。采用免疫组织化学法检测 EGFR 和 RASSF1A 的表达。通过直接基因组测序，对福尔马林固定石蜡包埋组织中提取的 DNA 进行 K-RAS 密码子 12 和 13 点突变和 BRAF 密码子 600 点突变分析。所有标本均为 EGFR 阳性表达，其过表达率为 92%。RASSF1A 表达率仅为 3.42%。EGFR 或 RASSF1A 的表达与肿瘤分级、pT 分期或淋巴结转移之间无显著相关性。对 94 例肿瘤组织进行了 KRAS 和 BRAF 突变检测分析，仅在 1 例样本中发现 KRAS 突变，未发现 BRAF V600E 点突变。综上所述，我们发现大多数阴茎 SCC 中存在 EGFR 过表达，但 RASSF1A 表达罕见，KRAS 突变罕见，阴茎 SCC 中不存在 BRAF 突变。这些数据表明，抗 EGFR 药物可能是阴茎 SCC 的潜在治疗选择。
