The expression of PTEN is associated with improved prognosis in patients with ampullary adenocarcinoma after pancreaticoduodenectomy.
The expression of PTEN is associated with improved prognosis in patients with ampullary adenocarcinoma after pancreaticoduodenectomy.
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DOI：
10.5858/arpa.2012-0418-oa
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发表时间：
2013-11
影响因子：
4.6
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Shroff S;Overman MJ;Rashid A;Shroff RT;Wang H;Chatterjee D;Katz MH;Lee JE;Wolff RA;Abbruzzese JL;Fleming JB;Wang H
磷酸酶和张力蛋白同源物（PTEN）是许多散发性肿瘤中最常失活的抑癌基因之一。PTEN的体细胞突变经常发生在许多肿瘤中，包括胃肠道和肝胆道的肿瘤。在转移性结肠腺癌、胃食管交界处腺癌、胃腺癌和胰腺导管腺癌患者中，PTEN表达缺失与不良预后相关。目的：探讨壶腹腺癌（AA）中PTEN的表达及其意义。我们构建了组织微阵列使用档案组织从92例（55名男性，37名女性）与以前未经治疗的AA谁经历了胰腺癌切除术在我们的机构。年龄范围为37至87岁（中位数：63岁）。用1.0 mm打孔器从代表性区域对每个肿瘤一式两份取样。通过免疫组织化学评价PTEN表达，并基于染色强度和阳性肿瘤细胞百分比进行半定量评分。染色结果与临床病理特征和生存率相关。92例中23例（25.0%）为PTEN阴性。AA中PTEN表达缺失与淋巴结转移（P= .004）、美国癌症联合委员会（AJCC）晚期（P= .02）和较高的复发频率（P= .03）相关。与肿瘤为PTEN阳性的患者相比，肿瘤为PTEN表达缺失的患者的无病生存期（DFS，平均：89.0 ± 20.8个月）和总生存期（OS，平均：93.1±19.1个月）较短（分别为平均DFS：161.4 ± 11.7个月，P= 0.02;平均OS：175.4 ±11.0个月，P = 0.002）。在多变量分析中，PTEN表达是DFS和OS的预后因素，与AJCC分期、淋巴结状态、病理肿瘤（pT）分期和分化无关。PTEN表达缺失与AA患者根治性手术后不良的无病生存率和总生存率相关。PTEN表达可作为AA患者手术切除后的预后指标。
Phosphatase and tensin homolog (PTEN) is one of the most frequently inactivated tumor suppressor genes in many sporadic cancers. Somatic mutations of PTEN occur frequently in many tumors including those of the gastrointestinal and hepatobiliary tracts. Loss of PTEN expression has been shown to be associated with poor prognosis in patients with metastatic colonic adenocarcinoma, gastroesophageal junction adenocarcinoma, gastric adenocarcinoma and pancreatic ductal adenocarcinoma. To study the expression of PTEN and its significance in ampullary adenocarcinoma (AA). We constructed tissue microarrays using archival tissue from 92 patients (55 males, 37 females) with previously untreated AA who underwent pancreaticoduodenectomy at our institution. The age range was 37 to 87 years (median: 63 years). Each tumor was sampled in duplicate with a 1.0 mm punch from representative areas. PTEN expression was evaluated by immunohistochemistry and scored semiquantitatively based on staining intensity and percentage positive tumor cells. Staining results were correlated with clinicopathologic features and survival. Twenty-three of 92 (25.0%) cases were PTEN-negative. Loss of PTEN expression in AA correlated with lymph node metastasis (P= .004), advanced American Joint Committee on Cancer (AJCC) stage (P= .02) and higher frequency of recurrence (P= .03). Patients whose tumors had loss of PTEN expression had shorter disease-free survival (DFS, mean: 89.0 ± 20.8 months) and overall survival (OS, mean: 93.1±19.1 months) compared to those whose tumors were PTEN-positive (mean DFS: 161.4 ± 11.7 months, P= .02; mean OS: 175.4 ±11.0 months, P = .002 respectively). In multivariate analyses, PTEN expression was a prognostic factor for both DFS and OS independent of AJCC stage, lymph node status, pathologic tumor (pT) stage, and differentiation. Loss of PTEN expression is associated with poor disease-free and overall survival in patients with AA after curative surgery. PTEN expression may be used as a prognostic marker for patients with resected AA.