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Expression of podocalyxin-like protein is an independent prognostic biomarker in resected esophageal and gastric adenocarcinoma.

ABSTRACT: 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.

SUBMITTER: Borg D

PROVIDER: S-EPMC4966733 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Expression of podocalyxin-like protein is an independent prognostic biomarker in resected esophageal and gastric adenocarcinoma.

Borg David D Hedner Charlotta C Nodin Björn B Larsson Anna A Johnsson Anders A Eberhard Jakob J Jirström Karin K

BMC clinical pathology 20160729

<h4>Background</h4>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.<h4>Methods</h4>The study cohort consists of a consecutive series of 174 patients with esophageal (including the gastroesophageal junction) or gastric adenocarcinoma, surgically treated ...[more]

PMID: 27478410

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Project description:BackgroundWe have previously shown that podocalyxin-like protein (PODXL) is a prognostic biomarker for poor survival in gastric and esophageal adenocarcinoma treated with surgery up-front. The aim of the present study was to assess PODXL expression in tumors from patients treated with neoadjuvant ± adjuvant (i.e. preoperative with or without postoperative) chemotherapy, with regard to histopathologic response, time to recurrence (TTR) and overall survival (OS).MethodsThe neoadjuvant cohort encompasses 148 consecutive patients who received neoadjuvant ± adjuvant chemotherapy for resectable gastric or esophageal adenocarcinoma between 2008 and 2014. Immunohistochemical expression of PODXL was assessed in pre-neoadjuvant biopsies, resected primary tumors and lymph node metastases. Histopathologic response was evaluated using the Chirieac grading. TTR and OS were estimated using Kaplan-Meier and Cox regression analyses. To investigate a potential predictive role for PODXL, the neoadjuvant cohort was pooled with the previously reported surgery up-front cohort.ResultsThe majority (> 95%) of the patients were treated with fluoropyrimidine- and oxaliplatin-based chemotherapy. Patients with high PODXL expression in their pre-neoadjuvant biopsies had a superior histopathologic response (notably 36% with no residual cancer cells) compared to those with negative or low PODXL expression, and were all recurrence-free at last follow-up. In the pooled cohort, no benefit of chemotherapy could be shown for PODXL negative cases, whereas PODXL positive (low or high) cases had a prolonged TTR and OS when treated with neoadjuvant ± adjuvant chemotherapy compared to surgery alone. The potential predictive role of PODXL was further strengthened for TTR in Cox regression analyses, especially for patients treated with neoadjuvant fluoropyrimidine and oxaliplatin for a minimum of 8 weeks, with a significant interaction term in both unadjusted (p = 0.006) and adjusted (p = 0.024) analyses. The interaction term was not statistically significant for overall survival.ConclusionsPatients with resectable gastric or esophageal adenocarcinoma with high PODXL expression in their diagnostic biopsies have an excellent prognosis when treated with neoadjuvant ± adjuvant fluoropyrimidine- and oxaliplatin-based chemotherapy. If the suggested predictive role of PODXL for benefit of chemotherapy can be confirmed, patients with PODXL negative tumors could be spared chemotherapy and treated with surgery alone.

Project description:BACKGROUND:Adenocarcinoma of the periampullary region is associated with poor prognosis and new prognostic and treatment predictive biomarkers are needed for improved treatment. Membranous expression of podocalyxin-like 1(PODXL), which is a cell-adhesion glycoprotein and stem cell marker, has been found to correlate with an aggressive tumour phenotype and adverse outcome in several cancer types. The aim of the present study was to examine the clinicopathological correlates, prognostic and predictive significance of tumour-specific PODXL expression in a retrospective cohort of pancreatic and periampullary carcinoma, morphologically divided into intestinal type (I-type) and pancreatobiliary type (PB-type) tumours. METHODS:Immunohistochemical expression of PODXL was analysed in tissue microarrays with primary tumours and a subset of paired lymph node metastases from 175 patients operated with pancreaticoduodenectomy for periampullary adenocarcinoma. Chi square test was applied to analyse the relationship between PODXL expression and clinicopathological parameters. Kaplan Meier analysis and Cox regression models were applied to estimate differences in 5-year overall survival (OS) and recurrence-free survival (RFS) in strata according to membranous and non-membranous PODXL expression. RESULTS:Membranous PODXL expression was significantly higher in primary PB-type (49.5 %) as compared with I-type (17.5 %) tumours. In PB-type tumours, PODXL expression was significantly associated with female sex (p = 0.005), location to the pancreas (p = 0.005), and poor differentiation grade (p = 0.044). Membranous PODXL expression was significantly associated with a reduced RFS (HR = 2.44, 95 % CI 1.10-5.44) and OS (HR = 2.32, 95 % CI 1.05-5.12) in I-type tumours and with a reduced RFS (HR = 1.63, 95 % CI 1.07-2.49) but not OS in PB-type tumours. PODXL remained a significant independent prognostic factor only in I-type tumours (HR = 5.12, 95 % CI 1.43-18.31 for RFS and HR = 7.31, 95 % CI 2.12-25.16 for OS). Patients with I-type tumours displaying membranous PODXL expression had a significant beneficial effect of adjuvant chemotherapy regarding 5-year OS. CONCLUSION:Membranous expression of PODXL is significantly higher in PB-type than in I-type periampullary adenocarcinomas and an independent factor of poor prognosis in the latter. The results further indicate a beneficial effect of adjuvant chemotherapy on I-type tumours with membranous PODXL expression, suggesting the potential utility of PODXL as a biomarker for improved treatment stratification of these patients.

Project description:INTRODUCTION: The polymeric immunoglobulin receptor (PIGR) has been proposed to be a candidate prognostic biomarker in a few cancer forms, and one previous study reported that reduced PIGR expression signifies more aggressive tumours of the distal esophagus and gastroesophageal junction (GEJ). In the present study, we examined the expression, clinicopathological correlates and prognostic significance of PIGR expression in an extended cohort of adenocarcinoma of the upper gastrointestinal tract. MATERIALS AND METHODS: Immunohistochemical PIGR expression was examined in a consecutive cohort of patients with surgically resected, radio-chemonaive adenocarcinoma of the esophagus, GE-junction and stomach (n?=?173), including paired samples of benign-appearing squamous epithelium (n?=?51), gastric mucosa (n?=?114), Barrett's esophagus (BE) or intestinal metaplasia (IM) (n?=?57) and lymph node metastases (n?=?75). Non-parametric tests were applied to explore associations between PIGR expression in primary tumours and clinicopathological characteristics. Classification and regression tree analysis was applied for selection of prognostic cut-off. The impact of PIGR expression on overall survival (OS) and recurrence-free survival (RFS) was assessed by Kaplan-Meier analysis and hazard ratios (HR) calculated by adjusted and unadjusted Cox proportional hazards modelling. RESULTS: PIGR expression was significantly higher in intestinal metaplasia (BE or gastric IM) compared to normal tissues and cancer (p?<?0.001). Reduced PIGR expression in primary tumours was significantly associated with more advanced tumour stage (p?=?0.002) and inversely associated with involved margins (p?=?0.034). PIGR expression did not differ between primary tumours and lymph node metastases. There was no significant difference in PIGR expression between tumours with and without a background of intestinal metaplasia. High PIGR expression was an independent predictor of a prolonged OS (HR?=?0.60, 95% CI 0.36-0.99) and RFS (HR?=?0.49, 95% CI 0.27-0.90) in patients with radically resected (R0) primary tumours and of an improved RFS (HR?=?0.32, 95% CI 0.15-0.69) in curatively treated patients with R0 resection/distant metastasis-free disease. CONCLUSION: High PIGR expression independently predicts a decreased risk of recurrence and an improved survival in patients with adenocarcinoma of the upper gastrointestinal tract. These findings are of potential clinical relevance and merit further validation.

Project description:BackgroundLung cancer is the leading cause of cancer-related death, and adenocarcinoma is the most common type of lung cancer. Although emerging evidence implicates the role of several aldehyde dehydrogenases in cancer progression, the expression and clinical significance of aldehyde dehydrogenase 3B1 in lung adenocarcinoma has never been studied.MaterialsIn our study, the expression of aldehyde dehydrogenase 3B1 in 250 cases of lung adenocarcinoma was detected with immunohistochemistry, and the patients were further divided into subgroups with different aldehyde dehydrogenase 3B1 expression. Using real-time polymerase chain reaction, we investigated the aldehyde dehydrogenase 3B1 messenger RNA in 20 lung adenocarcinoma and paired normal lung tissues. With the χ2 test, we evaluated the clinical significance of aldehyde dehydrogenase 3B1 by analyzing its correlation with the clinicopathological factors. Propensity score matching was performed to balance the baseline of cohort. With univariate and multivariate analyses, we screened the prognostic factors of lung adenocarcinoma and identified the independent prognostic factors before and after the propensity score matching.ResultsAldehyde dehydrogenase 3B1 expression was significantly associated with the sex and age of patients, tumor size, and histological grade. High expression of aldehyde dehydrogenase 3B1 predicted the poor prognosis (P = .003). Moreover, male patients (P = .020), large tumor size (P = .009), advanced T stage (P = .001), positive lymphatic invasion (P < .001), and advanced tumor-node-metastasis stage (P < .001) were all the prognostic factors for unfavorable outcome. Aldehyde dehydrogenase 3B1 was an independent prognostic biomarker of lung adenocarcinoma, indicating the poor prognosis. In addition, after balancing the baseline characteristics by propensity score matching, we also demonstrated that aldehyde dehydrogenase 3B1 was an independent prognostic biomarker of lung adenocarcinoma (P = .007).ConclusionsAldehyde dehydrogenase 3B1 was an independent prognostic biomarker of lung adenocarcinoma, indicating the unfavorable prognosis. Postoperative detection of aldehyde dehydrogenase 3B1 would help stratify the high-risk patients with lung adenocarcinoma and guide individual treatment.

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Expression of podocalyxin-like protein is an independent prognostic biomarker in resected esophageal and gastric adenocarcinoma.

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Expression of podocalyxin-like protein is an independent prognostic biomarker in resected esophageal and gastric adenocarcinoma.

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