Department of Internal Medicine Division of Hematology/Oncology Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, California, USA.
Cancer Med. 2013 Aug;2(4):496-506. doi: 10.1002/cam4.97. Epub 2013 Jun 10.
Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) negatively regulates the phosphoinositide-3-kinase (PI3K) signaling pathway. In colorectal cancer (CRC), observed frequencies of loss of PTEN expression, concordant expression in primary tumors and metastases, and the association of PTEN status with outcome vary markedly by detection method. We determined the degree to which PTEN expression is consistent in 70 matched human CRC primaries and liver metastases using a validated immunohistochemistry assay. We found loss of PTEN expression in 12.3% of assessable CRC primaries and 10.3% of assessable liver metastases. PTEN expression (positive or negative) was concordant in 98% of matched colorectal primaries and liver metastases. Next we related PTEN status to mutations in RAS and PI3K pathway genes (KRAS, NRAS, BRAF , and PIK3CA) and to overall survival (OS). PTEN expression was not significantly associated with the presence or absence of mutations in RAS or PI3K pathway genes. The median OS of patients whose tumors did not express PTEN was 9 months, compared to 49 months for patients whose tumors did express PTEN (HR = 6.25, 95% confidence intervals (CI) (1.98, 15.42), P = 0.0017). The association of absent PTEN expression with increased risk of death remained significant in multivariate analysis (HR = 6.31, 95% CI (2.03, 17.93), P = 0.0023). In summary, PTEN expression was consistent in matched CRC primaries and in liver metastases. Therefore, future investigations of PTEN in metastatic CRC can use primary tumor tissue. In patients with liver-only metastases, loss of PTEN expression predicted poor OS.
磷酸酶和张力蛋白同源物缺失于第 10 号染色体（PTEN）负调控磷酸肌醇-3-激酶（PI3K）信号通路。在结直肠癌（CRC）中，PTEN 表达缺失的观察频率、原发肿瘤和转移灶中的一致表达以及 PTEN 状态与结局的相关性因检测方法而异。我们使用经过验证的免疫组织化学检测方法，确定了 70 对匹配的人结直肠癌原发灶和肝转移灶中 PTEN 表达的一致性程度。我们发现，可评估的 CRC 原发灶中 PTEN 表达缺失率为 12.3%，可评估的肝转移灶中 PTEN 表达缺失率为 10.3%。98%的配对结直肠癌原发灶和肝转移灶的 PTEN 表达（阳性或阴性）是一致的。接下来，我们将 PTEN 状态与 RAS 和 PI3K 通路基因（KRAS、NRAS、BRAF 和 PIK3CA）的突变以及总生存期（OS）相关联。PTEN 表达与 RAS 或 PI3K 通路基因的存在或缺失无显著相关性。未表达 PTEN 的肿瘤患者的中位 OS 为 9 个月，而表达 PTEN 的肿瘤患者的中位 OS 为 49 个月（HR=6.25，95%置信区间（CI）（1.98，15.42），P=0.0017）。在多变量分析中，PTEN 表达缺失与死亡风险增加仍然相关（HR=6.31，95%CI（2.03，17.93），P=0.0023）。总之，匹配的 CRC 原发灶和肝转移灶中 PTEN 表达一致。因此，未来对转移性 CRC 中 PTEN 的研究可以使用原发肿瘤组织。在仅有肝转移的患者中，PTEN 表达缺失预测 OS 不良。
