David Borg, Charlotta Hedner, Björn Nodin, Anna Larsson, Anders Johnsson, Jakob Eberhard, Karin Jirström
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Immunohistochemical expression of PODXL was assessed in tissue microarrays with cores from primary tumors, lymph node metastases, intestinal metaplasia and adjacent normal epithelium. Survival analyses were performed on patients with no distant metastases and no macroscopic residual tumor.</p><p><strong>Results: </strong>In the majority of cases, expression of PODXL was significantly higher in cancer cells compared to normal epithelial cells and was significantly associated with lymph node metastases and high grade tumors. In esophageal adenocarcinoma, Kaplan-Meier analyses revealed that patients with PODXL negative tumors had a superior time to recurrence (TTR) and overall survival (OS) compared to patients with PODXL positive tumors. In gastric adenocarcinoma, patients with PODXL negative tumors had a superior TTR and a trend towards an improved OS. In esophageal and gastric adenocarcinoma combined, the prognostic significance of PODXL expression on TTR was confirmed in unadjusted Cox regression analysis (HR = 5.36, 95 % CI 1.68-17.06, p = 0.005) and remained significant in the adjusted model (HR = 3.39, 95 % CI 1.01-11.35, p = 0.048). Moreover, the impact of PODXL expression on OS was also confirmed in unadjusted analysis (HR = 2.52, 95 % CI 1.31-4.85, p = 0.006) and remained significant in the adjusted model (HR = 2.03, 95 % CI 1.04-3.98, p = 0.039).</p><p><strong>Conclusions: </strong>In esophageal and gastric adenocarcinoma, PODXL expression is an independent prognostic biomarker for reduced time to recurrence and poor overall survival. This is the first report on the prognostic role of PODXL in esophageal adenocarcinoma and validates recent findings in gastric cancer.</p>","PeriodicalId":35804,"journal":{"name":"BMC Clinical Pathology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2016-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12907-016-0034-8","citationCount":"29","resultStr":"{\"title\":\"Expression of podocalyxin-like protein is an independent prognostic biomarker in resected esophageal and gastric adenocarcinoma.\",\"authors\":\"David Borg, Charlotta Hedner, Björn Nodin, Anna Larsson, Anders Johnsson, Jakob Eberhard, Karin Jirström\",\"doi\":\"10.1186/s12907-016-0034-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Podocalyxin-like protein (PODXL) is a cell surface transmembrane glycoprotein, the expression of which has been associated with poor prognosis in a range of malignancies. The aim of this study was to investigate the impact of PODXL expression on survival in esophageal and gastric adenocarcinoma.</p><p><strong>Methods: </strong>The study cohort consists of a consecutive series of 174 patients with esophageal (including the gastroesophageal junction) or gastric adenocarcinoma, surgically treated between 2006 and 2010 and not subjected to neoadjuvant treatment. Immunohistochemical expression of PODXL was assessed in tissue microarrays with cores from primary tumors, lymph node metastases, intestinal metaplasia and adjacent normal epithelium. Survival analyses were performed on patients with no distant metastases and no macroscopic residual tumor.</p><p><strong>Results: </strong>In the majority of cases, expression of PODXL was significantly higher in cancer cells compared to normal epithelial cells and was significantly associated with lymph node metastases and high grade tumors. In esophageal adenocarcinoma, Kaplan-Meier analyses revealed that patients with PODXL negative tumors had a superior time to recurrence (TTR) and overall survival (OS) compared to patients with PODXL positive tumors. In gastric adenocarcinoma, patients with PODXL negative tumors had a superior TTR and a trend towards an improved OS. In esophageal and gastric adenocarcinoma combined, the prognostic significance of PODXL expression on TTR was confirmed in unadjusted Cox regression analysis (HR = 5.36, 95 % CI 1.68-17.06, p = 0.005) and remained significant in the adjusted model (HR = 3.39, 95 % CI 1.01-11.35, p = 0.048). 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引用次数: 29
摘要
背景:Podocalyxin-like protein (PODXL)是一种细胞表面跨膜糖蛋白，其表达与一系列恶性肿瘤的不良预后相关。本研究的目的是探讨PODXL表达对食管癌和胃腺癌患者生存的影响。方法:研究队列由连续174例食管癌(包括胃食管交界处)或胃腺癌患者组成，这些患者在2006年至2010年间接受过手术治疗，未接受新辅助治疗。通过组织微阵列检测PODXL的免疫组织化学表达，这些微阵列的核心来自原发肿瘤、淋巴结转移、肠化生和邻近的正常上皮。对无远处转移和肉眼无肿瘤残留的患者进行生存分析。结果:在大多数情况下，PODXL在癌细胞中的表达明显高于正常上皮细胞，并与淋巴结转移和高分级肿瘤显著相关。在食管腺癌中，Kaplan-Meier分析显示，与PODXL阳性肿瘤患者相比，PODXL阴性肿瘤患者的复发时间(TTR)和总生存期(OS)更优越。在胃腺癌中，PODXL阴性肿瘤患者的TTR更高，OS也有改善的趋势。在合并食管癌和胃腺癌中，未经校正的Cox回归分析证实了PODXL表达对TTR的预后意义(HR = 5.36, 95% CI 1.68 ~ 17.06, p = 0.005)，在校正模型中仍然具有显著意义(HR = 3.39, 95% CI 1.01 ~ 11.35, p = 0.048)。此外，未经调整的分析也证实了PODXL表达对OS的影响(HR = 2.52, 95% CI 1.31-4.85, p = 0.006)，并且在调整模型中仍然具有显著性(HR = 2.03, 95% CI 1.04-3.98, p = 0.039)。结论:在食管癌和胃腺癌中，PODXL表达是复发时间缩短和总生存期差的独立预后生物标志物。这是关于PODXL在食管癌中的预后作用的第一篇报道，并验证了最近在胃癌中的发现。
Expression of podocalyxin-like protein is an independent prognostic biomarker in resected esophageal and gastric adenocarcinoma.
Background: Podocalyxin-like protein (PODXL) is a cell surface transmembrane glycoprotein, the expression of which has been associated with poor prognosis in a range of malignancies. The aim of this study was to investigate the impact of PODXL expression on survival in esophageal and gastric adenocarcinoma.
Methods: The study cohort consists of a consecutive series of 174 patients with esophageal (including the gastroesophageal junction) or gastric adenocarcinoma, surgically treated between 2006 and 2010 and not subjected to neoadjuvant treatment. Immunohistochemical expression of PODXL was assessed in tissue microarrays with cores from primary tumors, lymph node metastases, intestinal metaplasia and adjacent normal epithelium. Survival analyses were performed on patients with no distant metastases and no macroscopic residual tumor.
Results: In the majority of cases, expression of PODXL was significantly higher in cancer cells compared to normal epithelial cells and was significantly associated with lymph node metastases and high grade tumors. In esophageal adenocarcinoma, Kaplan-Meier analyses revealed that patients with PODXL negative tumors had a superior time to recurrence (TTR) and overall survival (OS) compared to patients with PODXL positive tumors. In gastric adenocarcinoma, patients with PODXL negative tumors had a superior TTR and a trend towards an improved OS. In esophageal and gastric adenocarcinoma combined, the prognostic significance of PODXL expression on TTR was confirmed in unadjusted Cox regression analysis (HR = 5.36, 95 % CI 1.68-17.06, p = 0.005) and remained significant in the adjusted model (HR = 3.39, 95 % CI 1.01-11.35, p = 0.048). Moreover, the impact of PODXL expression on OS was also confirmed in unadjusted analysis (HR = 2.52, 95 % CI 1.31-4.85, p = 0.006) and remained significant in the adjusted model (HR = 2.03, 95 % CI 1.04-3.98, p = 0.039).
Conclusions: In esophageal and gastric adenocarcinoma, PODXL expression is an independent prognostic biomarker for reduced time to recurrence and poor overall survival. This is the first report on the prognostic role of PODXL in esophageal adenocarcinoma and validates recent findings in gastric cancer.
期刊介绍：
BMC Clinical Pathology is an open access journal publishing original peer-reviewed research articles in all aspects of histopathology, haematology, clinical biochemistry, and medical microbiology (including virology, parasitology, and infection control). BMC Clinical Pathology (ISSN 1472-6890) is indexed/tracked/covered by PubMed, CAS, EMBASE, Scopus and Google Scholar.
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