[Show abstract][Hide abstract] ABSTRACT: Introduction. Glucose-regulated protein 78 (78 kDa, GRP78), which is also known as immunoglobulin heavy chain binding protein (BIP), is a major chaperone in the endoplasmic reticulum (ER). The expression and clinical significance of GRP78 in the serum of non-small cell lung cancer patients have not yet been clearly described. The aims of the present study were to investigate the expression of GRP78 in the serum of non-small cell lung cancer patients, the relationships with clinicopathological parameters, and the potential implications for survival. Patients and Methods. A total of 163 peripheral blood samples from non-small cell lung cancer patients were prospectively collected at the Department of Thoracic Surgery, Fudan University Shanghai Cancer, China. Clinical characteristics data, including age, gender, stage, overall survival (OS) time, and relapse-free survival (RFS) time, were also collected. Serum GRP78 levels were measured using a commercially available ELISA kit. The associations between GRP78 levels and clinicopathological characteristics and survival were examined using Student's t-test, Kaplan-Meier, or Cox regression analyses. Results. The mean ± standard error (SE) value of GRP78 was 326.5 ± 49.77 pg/mL. This level was significantly lower compared with the level in late-stage non-small cell lung cancer patients (1227 ± 223.6, p = 0.0001). There were no significant correlations with the clinicopathological parameters. No significant difference was found between high GRP78 expression and low GRP78 expression with regard to RFS (p = 0.1585). However, the OS of patients with higher GRP78 expression was significantly poorer (p = 0.0334). Conclusions. GRP78 was expressed in non-small cell lung cancer patients and was highly enriched in late-stage lung cancer. GRP78 may have an important role in the carcinogenesis of non-small cell lung cancer and may be a prognostic marker for non-small cell lung cancer.
[Show abstract][Hide abstract] ABSTRACT: Background:
Recent studies have revealed that clusterin is implicated in many physiological and pathological processes, including tumorigenesis. However, the relationship between serum clusterin expression and esophageal squamous cell carcinoma (ESCC) is unclear.
The serum clusterin concentrations of 87 ESCC patients and 136 healthy individuals were examined. An independent-samples Mann-Whitney U test was used to compare serum clusterin concentrations of ESCC patients to those of healthy controls. Univariate analysis was conducted using the log-rank test and multivariate analyses were performed using the Cox proportional hazards model.
In healthy controls, the mean clusterin concentration was 288.8 ± 75.1 μg/mL, while in the ESCC patients, the mean clusterin concentration was higher at 412.3 ± 159.4 μg/mL (P < 0.0001). The 1-, 2-, and 4-year survival rates for the 87 ESCC patients were 89.70%, 80.00%, and 54.50%. Serum clusterin had an optimal diagnostic cut-off point (serum clusterin concentration = 335.5 μg/mL) for esophageal squamous cell carcinoma with sensitivity of 71.26% and specificity of 77.94%. And higher serum clusterin concentration (>500 μg/mL) indicated better prognosis (P = 0.030).
Clusterin may play a key role during tumorigenesis and tumor progression of ESCC and it could be applied in clinical work as a tumor marker and prognostic factor.
[Show abstract][Hide abstract] ABSTRACT: Background:
A consensus treatment strategy for patients with esophageal squamous cell carcinoma (ESCC) that recurs after definitive esophagectomy has not been established. This study compared outcomes in ESCC patients who underwent salvage lymphadenectomy and those who underwent salvage radiotherapy/chemoradiotherapy for recurrence in cervical lymph nodes.
Clinical characteristics of 79 patients were analyzed. Overall survival was calculated from the day of salvage treatment to the time of death or last follow-up. Survival rates were estimated using the Kaplan-Meier method, and statistical analysis was performed using the log-rank test for equality of the survival curves. The χ (2) test was used to compare patient and tumor characteristics. Univariate analysis was performed using the log-rank test, and multivariate analysis was performed using the Cox proportional hazards model.
Initial treatment against recurrence (salvage lymphadenectomy vs. salvage radiotherapy or chemoradiotherapy) was the only significant prognostic factor with a hazard ratio of 2.358 and 95 % confidence interval of 1.067-5.210. Survival curves were significantly different between patients receiving salvage surgery and those receiving salvage radiotherapy/chemoradiotherapy (p = 0.0269).
Compared with salvage radiotherapy/radiochemotherapy, salvage cervical lymphadenectomy might be the main treatment for esophageal carcinoma patients who developed cervical lymph node recurrence after curative esophagectomy.
[Show abstract][Hide abstract] ABSTRACT: Objectives:
Controversy persists regarding the adequate extent of lymph node (LN) dissection in thoracic esophageal cancer (EC) surgery. Oncologic efficacy should be balanced with the increased risk of postoperative complications after aggressive radical LN dissection. Here, we evaluate the effectiveness of common hepatic artery LN dissection in surgery for thoracic esophageal squamous cell carcinoma.
Patients and methods:
Among a total of 1,563 EC patients who underwent surgery from May 2005 to December 2012 at the Fudan University Shanghai Cancer Center, 1,248 thoracic esophageal squamous cell carcinoma were selected for this study, including 682 patients who underwent esophagectomy with common hepatic artery LN dissection and 566 patients who underwent esophagectomy without common hepatic artery LN dissection. The clinical data of patients were retrospectively analyzed. In addition, the locoregional LN metastasis, relationship between metastatic rates of common hepatic artery LN and clinicopathological factors were analyzed. A propensity score match analysis were performed to control for potential differences in the characteristics of patients with EC cell carcinoma, and postoperative complications were analyzed after propensity score-matching.
The metastatic rate of common hepatic LN was 3.5%. Logistic regression analysis revealed tumor diameter, N classification and pTNM stage were risk factors for common hepatic LN metastasis. Matching based on propensity scores produced 361 patients in each group. The overall incidence of postoperative complications was 32.70% and 35.45%, respectively, no significant difference was found (P=0.432).
The metastatic rate of common hepatic artery LN is low. For patients who undergo resection for Stage I thoracic esophageal squamous cell carcinoma, the dissection of common hepatic artery LN may be safely omitted.
[Show abstract][Hide abstract] ABSTRACT: HER2/neu alteration detection in breast cancer is important for decision making of the HER2-targeted therapy. We retrospectively analyzed the HER2/neu status by fluorescence in situ hybridization and HER2 protein expression by immunohistochemistry in a cohort of 481 patients with invasive breast cancer. Fluorescence in situ hybridization showed that 57.4% of cases exhibited HER2 amplification but 41.4% did not, and 1.2% exhibited an equivocal status. Immunohistochemistry showed that 10.4%, 16.8%, 38.3%, and 34.5% of cases had scores of 0, 1+, 2+, and 3+, respectively. The HER2 status showed a moderate agreement with HER2 expression with a score of 0, 1+, and 3+ (κ = 0.576, P < .05), and the concordance rate was 90%, 61.7%, and 83.1%, respectively. The HER2 amplification occurred more likely in cases with higher immunohistochemistry scores (P < .001), and polysomy 17 was observed in 28.3% of cases, but more frequently in the HER2 amplification subgroup (33.3%) than in the HER2 nonamplification subgroup (20.1%) (P < .05). There was no significant correlation between the frequency of polysomy 17 and immunohistochemistry scores (P > .05). In the immunohistochemistry 2+ group, 56.5% cases showed HER2/neu amplification, and polysomy 17 occurred more likely in the HER2 amplification subgroup (34.6%) than in the HER2 nonamplification group (13.0%) (P < .001). We concluded that the HER2 status was correlated with HER2 protein expression levels, and it is necessary to determine the HER2 status for cases with immunohistochemistry 2+. The frequency of polysomy 17 was correlated with the HER2 copy number and partially contributed to HER2/neu amplification but not HER2 protein expression.
Human pathology 06/2011; 42(10):1499-504. DOI:10.1016/j.humpath.2010.04.023 · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Clusterin is an enigmatic glycoprotein with a nearly ubiquitous tissue distribution. It plays important roles in various pathophysiological processes, including tissue remodeling, reproduction, lipid transport, complement regulation, and apoptosis. Clusterin appears to have two main isoforms that result from alternative splicing. The secreted and nuclear forms of clusterin have been reported to play different roles in human malignancies. The purpose of this study was to examine clusterin immunoexpression and its clinical significance in a group of Chinese patients with non-small cell lung cancer (NSCLC). Tissue samples from the primary tumors of 121 patients with completely resected NSCLC were obtained. Clusterin protein expression was evaluated by immunohistochemical staining with an antibody against all clusterin isoforms. Staining patterns were observed and graded based on intensity and density and were correlated with clinical and pathological data. Both cytoplasmic and nuclear clusterin immunostaining patterns were observed. Clusterin staining was observed only in the cytoplasm in 70 patients (57.9%), only in the nucleus in 27 patients (22.3%), and in both the cytoplasm and nucleus in 16 patients (13.2%). A significant association was observed between positive cytoplasmic clusterin expression and histologic type as indicated by adenocarcinomas that were more likely to have clusterin staining only in the cytoplasm. Clusterin immunostaining was neither associated with recurrence-free survival (RFS) nor overall survival of patients by univariate or multivariate analysis. For patients undergoing chemotherapy, those with only cytoplasmic clusterin staining had worse survival than other patients. In conclusion, both cytoplasmic and nuclear immunostaining patterns of clusterin were detected in the tumors of patients with NSCLC. Adenocarcinomas were more likely to have only cytoplasmic staining. The immunoexpression of clusterin was not associated with prognosis, and cytoplasm-only immunostaining of clusterin was inversely correlated with chemosensitivity in this group of patients.
Beiträge zur Klinik der Tuberkulose 10/2010; 188(5):423-31. DOI:10.1007/s00408-010-9248-1 · 2.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate CK19, RET, galectin-3 and HBME-1 expression in papillary thyroid carcinoma (PTC) and to evaluate their diagnostic significance.
155 PTC specimens and 83 other diseased-thyroid specimens were collected. Immunohistochemistry for CK19, RET, galectin-3 and HBME-1 was performed.
The 155 PTC cases were classified into eight variants according to the WHO classification, including 74 cases of classic PTC, 40 cases of papillary microcarcinoma, and rare variants. CK19, RET, galectin-3 and HBME-1 expression was 87.1% (135/155), 71.0% (110/155), 91.6% (142/155), and 95.5% (148/155), respectively, for the PTC group; expression of all these markers was much higher than that in the control group (p<0.05). However, the expression of these markers did not differ among the variants (p>0.05). The expression of these markers, particularly CK19 and RET, was diffuse and strong in the papillary structure of PTC, but weak and focal in the papilla of tissue with benign disease. The expression of CK19 in follicular PTC was significantly higher than in follicular thyroid carcinoma (FTC) (p<0.05).
CK19, RET, galectin-3 and HBME-1 expression in PTC was higher than that in benign disease cases, but these were not specific markers for PTC. In summary, combining markers can increase the reliability and differential diagnosis of PTC. It is also worth noting that CK19 was very useful not only for the differentiation of benign and malignant papillary structure but also for the differential diagnosis of follicular PTC and FTC.
[Show abstract][Hide abstract] ABSTRACT: Despite multidisciplinary treatment, lung cancer remains a highly lethal disease due to poor response to chemotherapy. The identification of therapeutic agents with synergistic effects with traditional drugs is an alternative for lung cancer therapy. In this study, the synergistic effects of arsenic trioxide (As2O3) with cisplatin (DDP) on A549 and H460 non-small cell lung cancer (NSCLC) cells were explored.
A549 and H460 human lung cancer cells were treated with As2O3 and/or DDP. Cell growth curves, cell proliferation, cell cycle, and apoptosis of human cancer cell lines were determined by the 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) method, clonogenic assay, and flow cytometry (FCM). Apoptosis was further assessed by TUNEL staining. Cell cycle and apoptosis related protein p21, cyclin D1, Bcl-2, bax, clusterin, and caspase-3 were detected by western blot.
MTT and clonogenic assay showed As2O3 within 10(-2) microM to 10 microM exerted inhibition on the proliferation of NSCLC cells, and 2.5 microM As2O3 exerted synergistic inhibition on proliferation with 3 microg/ml DDP. The combination indices (CI) for A549 and H460 were 0.5 and 0.6, respectively, as confirmed by the synergism of As2O3 with DDP. FCM showed As2O3 did not affect the cell cycle. The G0/G1 fraction ranged from 57% to 62% for controlled A549 cells and cells treated with As2O3 and/or DDP. The G0/G1 fraction ranged from 37% to 42% for controlled H460 cells and cells treated with As2O3 and/or DDP. FCM and TUNEL staining illustrated that the combination of As2O3 and DDP provoked synergistic effects on apoptosis induction based on the analysis of the apoptosis index. Western blotting revealed that the expression of cell cycle related protein p21 and cyclin D1 were not affected by the treatments, whereas apoptosis related protein bax, Bcl-2, and clusterin were significantly regulated by As2O3 and/or DDP treatments compared with controls. The expression of caspase-3 in cells treated with the combination of As2O3 and DDP did not differ from that in cells treated with a single agent.
As2O3 exerted synergistic effects with DDP on NSCLC cells, and the synergistic effects were partly due to the induction of caspase-independent apoptosis.
Journal of Experimental & Clinical Cancer Research 09/2009; 28(1):110. DOI:10.1186/1756-9966-28-110 · 4.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to identify clinical risk factors and establish a prediction scoring system for locally advanced rectal cancer.
Retrospective univariate and multivariate logistic analyses were conducted for 413 curable rectal cancer patients. Clinical factors found to be significantly related with tumor stages were incorporated into a scoring system to predict locally advanced stages, which was validated in an independent cohort of 279 rectal cancer patients.
In the training set, tumor size, differentiation, and serum carcinoembryonic antigen (CEA) level (P < 0.01) were significant predictors of locally advanced rectal cancer in both univariate and multivariate analyses, which were incorporated into a proposed scoring system to predict locally advanced stages. The area under the receiver operating characteristic curve (AUROC) of this scoring system was 0.751 and the prediction accuracy was 78.2%. Patients were categorized into three subsets according to the total score. The low-risk group (score 0) had a smaller chance (18.2%) to have locally advanced rectal cancer, compared to mean 49.2% for the intermediate-risk group (score 1) and mean 83.0% for the high-risk group (score of 2-4; P < 0.05). In the validation set, the AUROC of the scoring system was 0.756 and the prediction accuracy was 75.3%.
Tumor size more than 2 cm, poor differentiation, and elevated serum CEA level are high-risk factors of locally advanced rectal cancer. A simple scoring system based on these three factors may be valuable to predict locally advanced rectal cancer.
Journal of Gastrointestinal Surgery 04/2009; 13(7):1299-305. DOI:10.1007/s11605-009-0892-9 · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report the detailed molecular study of angiogenesis-ralated genes and target therapy of the case of a male 46-year-old patient with extrarenal rhabdoid tumor of pelvic retroperitoneum. The patient was found to have a huge pelvic soft tissue sarcoma and underwent pelvic tumorectomy and appendectomy. The microscopically morphological features and molecular profile by immunohistochemical analysis supported the surgical histological diagnosis of extrarenal rhabdoid tumor. The tumor recurred two weeks after surgery and metastasized to the lung, left abdominal wall and mesenteric lymph nodes. Systemic chemotherapy including ifosfamide, liposomal doxorubicin, Taxol and cisplatin, concurrently with pelvic radiotherapy (58 Gy of total dose). However, the patient did not respond to the combination of chemotherapy and radiotherapy. Immunohistochemical staining and fluorescence in situ hybridization of tumor cells indicated negative expression of human epidermal growth factor receptor-2 (HER-2) and epidermal growth factor receptor (EGFR) and positive expression of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR). So anti-VEGF targeted therapy (Bevacizumab) was administered following the fourth course chemotherapy. However, the condition worsened after the administration of the second cycle of Bevacizumab. Multiple organ failure led to the death of the patient. The patient only survived five months and 20 days after the surgery of the primary tumor.