Department of Surgery, Creighton University Medical Center, Omaha, NE, USA.
J Surg Res. 2013 Mar;180(1):97-103. doi: 10.1016/j.jss.2012.10.053. Epub 2012 Nov 20.
Little information exists on Kras mutations and p53 overexpression in pseudomyxoma peritonei (PMP). These genetic alterations are associated with poorer prognoses in colorectal cancer. We postulated that these mutations might be more frequent in high-grade (HG) PMP (peritoneal mucinous carcinomatosis) versus low-grade (LG) PMP (disseminated peritoneal adenomucinosis/peritoneal mucinous carcinomatosis), for which survival differences are well documented.
We collected data retrospectively on patients with PMP of appendiceal origin tested for Kras mutation (commercial assay) and p53 overexpression (immunohistochemistry). We used Fisher's exact test, chi-square test, and Kaplan-Meier survival curves for analysis.
Of 64 cases with Kras mutations, 25 were classified as LG and 39 as HG PMP. Median age at diagnosis was 53 ± 11.5 y. We detected Kras mutations in 37 of 64 patients (57.8%). In LG PMP, 15 of 25 (60%) were Kras mutant versus 22 of 39 (56.4%) in HG PMP (P=0.80). Nearly 89% of mutations were seen in codon 12. We noted overexpression of p53 in 44.3% (86 of 194) of patients overall, which was significantly different between LG PMP and HG PMP: 35.5% (37 of 104) versus 54.4% (49 of 90), respectively (P=0.009). Kras mutations did not affect prognosis. Overexpression of p53 was associated with a worse outcome.
Kras mutation and p53 overexpression rates are comparable to those of colorectal adenomas and mucinous colorectal cancer. Codon 12 mutations may be associated with mucin production. Kras mutation status is not prognostic for overall survival. Overexpression of p53 was significantly correlated with female sex, higher-grade disease, and worse survival.
在腹膜假黏液瘤（PMP）中，Kras 突变和 p53 过表达的信息很少。这些基因改变与结直肠癌的预后较差有关。我们假设这些突变在高级别（HG）PMP（腹膜黏液性癌病）中比低级别（LG）PMP（弥漫性腹膜黏液腺癌/腹膜黏液性癌病）更为常见，因为后者的生存差异已有很好的记录。
我们回顾性地收集了阑尾来源的 PMP 患者的检测数据，这些患者的检测项目包括 Kras 突变（商业检测）和 p53 过表达（免疫组化）。我们使用 Fisher 精确检验、卡方检验和 Kaplan-Meier 生存曲线进行分析。
在 64 例有 Kras 突变的病例中，25 例为 LG PMP，39 例为 HG PMP。诊断时的中位年龄为 53±11.5 岁。我们在 64 例患者中的 37 例（57.8%）中检测到了 Kras 突变。在 LG PMP 中，15 例（60%）为 Kras 突变，而在 HG PMP 中，22 例（56.4%）为 Kras 突变（P=0.80）。近 89%的突变发生在密码子 12。我们发现，总体而言，p53 过表达在 44.3%（194 例中的 86 例）的患者中，LG PMP 和 HG PMP 之间存在显著差异：分别为 35.5%（104 例中的 37 例）和 54.4%（90 例中的 49 例）（P=0.009）。Kras 突变并未影响预后。p53 过表达与较差的结局相关。
Kras 突变和 p53 过表达的发生率与结直肠腺瘤和黏液性结直肠癌相似。密码子 12 的突变可能与黏蛋白的产生有关。Kras 突变状态与总生存无关。p53 过表达与女性、高级别疾病和较差的生存显著相关。
