Oki Eiji, Kakeji Yoshihiro, Baba Hideo, Tokunaga Eriko, Nakamura Toshihiko, Ueda Naoyuki, Futatsugi Motonori, Yamamoto Manabu, Ikebe Masahiko, Maehara Yoshihiko
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka, Japan.
J Gastroenterol Hepatol. 2006 May;21(5):814-8. doi: 10.1111/j.1440-1746.2005.04028.x.
Encoding phosphate and tensin homolog (PTEN) is a cancer suppressor gene and it has been assumed that gene mutation and loss of heterozygosity (LOH) occurs frequently in various types of carcinoma. However, the role of LOH of PTEN and its outcome variables in gastric cancer have not been well established. In the present study, we investigated the roles of PTEN, LOH and their outcomes.
Fresh frozen tumor samples from 119 gastric cancer patients with a primary diagnosis of gastric carcinoma were evaluated for LOH of PTEN using an automated sequencer. Results were compared with pathological parameters. The median follow-up period was 559 days.
Loss of heterozygosity of PTEN was observed in 17.1% of patients (13/76) diagnosed with gastric cancer. No particular relationship was found with any clinicopathological factor. However, the prognosis of patients with LOH of PTEN was significantly poor. Multivariate analyses revealed that vascular invasion, invasion depth, LOH of PTEN, histology and lymph node metastasis were correlated with survival of the patient.
Even though mutation of PTEN in gastric cancer has rarely been reported, according to our findings, LOH of PTEN frequently occurs in gastric cancers and is correlated with disease-related deaths. The LOH of PTEN is an independent prognostic factor and PTEN is a candidate as a haploinsufficient tumor suppressor in gastric cancers.
磷酸酶和张力蛋白同源物(PTEN)编码基因是一种抑癌基因,人们认为其基因突变和杂合性缺失(LOH)在各种类型的癌症中频繁发生。然而,PTEN的杂合性缺失及其在胃癌中的预后变量的作用尚未完全明确。在本研究中,我们调查了PTEN、LOH及其预后情况。
对119例初诊为胃癌的患者的新鲜冷冻肿瘤样本,使用自动测序仪评估PTEN的杂合性缺失情况。将结果与病理参数进行比较。中位随访期为559天。
在诊断为胃癌的患者中,17.1%(13/76)观察到PTEN杂合性缺失。未发现与任何临床病理因素有特定关系。然而,PTEN杂合性缺失患者的预后明显较差。多因素分析显示,血管侵犯、浸润深度、PTEN杂合性缺失、组织学类型和淋巴结转移与患者生存相关。
尽管胃癌中PTEN突变鲜有报道,但根据我们的研究结果,PTEN杂合性缺失在胃癌中频繁发生,且与疾病相关死亡有关。PTEN杂合性缺失是一个独立的预后因素,PTEN是胃癌中半合子不足的肿瘤抑制候选基因。