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PTEN 的表达与胰十二指肠切除术后壶腹腺癌患者的预后改善相关。

The expression of PTEN is associated with improved prognosis in patients with ampullary adenocarcinoma after pancreaticoduodenectomy.

机构信息

From the Departments of Pathology (Drs S. Shroff, Rashid, and Huamin Wang), Gastrointestinal Medical Oncology (Drs Overman, R. T. Shroff, Hua Wang, Wolff, and Abbruzzese), and Surgical Oncology (Drs Chatterjee, Katz, Lee, and Fleming). The University of Texas M. D. Anderson Cancer Center, Houston.

出版信息

Arch Pathol Lab Med. 2013 Nov;137(11):1619-26. doi: 10.5858/arpa.2012-0418-OA.

Abstract

CONTEXT

Phosphatase and tensin homolog (PTEN) is one of the most frequently inactivated tumor suppressor genes in sporadic cancers. Somatic mutations of PTEN occur in many tumors including those of the gastrointestinal and hepatobiliary tracts. Loss of PTEN expression is associated with poor prognosis in patients with metastatic colonic adenocarcinoma, gastroesophageal junction adenocarcinoma, gastric adenocarcinoma, and pancreatic ductal adenocarcinoma.

OBJECTIVE

To study the expression of PTEN and its significance in ampullary adenocarcinoma (AA).

DESIGN

We constructed tissue microarrays by using archival tissue from 92 patients (55 males, 37 females; median age, 63 years; age range, 37 to 87 years) with previously untreated AA who underwent pancreaticoduodenectomy at our institution. PTEN expression was evaluated by immunohistochemistry, scored semiquantitatively (based on staining intensity and percentage positive tumor cells), and correlated with clinicopathologic features and survival.

RESULTS

Of 92 cases, 23 (25.0%) were PTEN negative. Loss of PTEN expression 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 with PTEN-negative tumors had shorter disease-free survival (DFS, mean: 89.0 ± 20.8 months) and overall survival (OS, mean: 93.1 ± 19.1 months) than those with PTEN-positive tumors (DFS, mean: 161.4 ± 11.7 months, P = .01; OS, mean: 175.4 ± 11.0 months, P = .001). 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.

CONCLUSIONS

Loss of PTEN expression is associated with poor DFS and OS in patients with AA after curative surgery. PTEN expression may be used as a prognostic marker for patients with resected AA.

摘要

背景

磷酸酶和张力蛋白同源物(PTEN)是散发性癌症中最常失活的肿瘤抑制基因之一。PTEN 的体细胞突变发生在许多肿瘤中,包括胃肠道和肝胆道肿瘤。PTEN 表达缺失与转移性结直肠腺癌、胃食管交界处腺癌、胃腺癌和胰腺导管腺癌患者的预后不良相关。

目的

研究 PTEN 在壶腹腺癌(AA)中的表达及其意义。

设计

我们使用来自 92 例未经治疗的 AA 患者的存档组织构建了组织微阵列,这些患者在我们的机构接受了胰十二指肠切除术。通过免疫组织化学评估 PTEN 表达,进行半定量评分(基于染色强度和阳性肿瘤细胞百分比),并与临床病理特征和生存相关联。

结果

在 92 例病例中,有 23 例(25.0%)为 PTEN 阴性。PTEN 表达缺失与淋巴结转移相关(P =.004)、美国癌症联合委员会(AJCC)分期较晚(P =.02)和更高的复发频率相关(P =.03)。PTEN 阴性肿瘤患者的无病生存(DFS,平均:89.0 ± 20.8 个月)和总生存(OS,平均:93.1 ± 19.1 个月)均短于 PTEN 阳性肿瘤患者(DFS,平均:161.4 ± 11.7 个月,P =.01;OS,平均:175.4 ± 11.0 个月,P =.001)。在多变量分析中,PTEN 表达是 DFS 和 OS 的独立预后因素,与 AJCC 分期、淋巴结状态、病理肿瘤(pT)分期和分化无关。

结论

在根治性手术后,PTEN 表达缺失与 AA 患者的 DFS 和 OS 不良相关。PTEN 表达可作为 AA 患者的预后标志物。

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