Tian-You Wang

SLP-2 overexpression is associated with tumour distant metastasis and poor prognosis in pulmonary squamous cell carcinoma

Objective: To investigate the role of stomatin-like protein 2 (SLP-2), a novel cancer-related gene, in pulmonary squamous cell carcinoma (PSCC) and its implications. Methods: Immunohistochemical detection of SLP-2 was performed on 96 cases of PSCC with a tissue microarray. Results: SLP-2 was overexpressed in lung cancer compared with normal lung tissue (p <0.001). High-level SLP-2 expression was significantly correlated with distant metastasis (p = 0.025), decreased overall survival (p = 0.018) and disease-free survival (p = 0.017). SLP-2 overexpression was an independent prognostic factor in multivariate analysis using the Cox regression model (p <0.05). Conclusion: SLP-2 overexpression is associated with tumour distant metastasis and poor prognosis in PSCC. SLP-2 could be regarded as a new significant prognostic biomarker for patients with PSCC.

Radical systematic mediastinal lymphadenectomy versus mediastinal lymph node sampling in patients with clinical stage IA and pathological stage T1 non-small cell lung cancer

PurposeTo explore the appropriate method of mediastinal lymph node dissection for selected clinical stage IA (cIA) non-small cell lung cancer (NSCLC).MethodsFrom 1998 through 2002, the curative-intent surgery was performed to 105 patients with cIA NSCLC who had been postoperatively identified as pathologic-stage T1. According to the method of intraoperative medistinal lymph node dissection, they were divided into radical systematic mediastinal lymphadenectomy (LA) group (n = 42) and mediastinal lymph-node sampling (LS) group (n = 63). The effects of LS and LA on morbidity, N staging, overall survival (OS) and disease-free survival (DFS) were investigated. Also, associations between clinicopathological parameters and survival were analyzed.ResultsThe mean numbers of dissected lymph nodes per patient in the LA group was significantly greater than that in the LS group (15.59 ± 3.08 vs. 6.46 ± 2.21, P < 0.001), and the postoperative overall morbidity rate was higher in the LA group than that in the LS group (26.2 vs. 11.1%, P = 0.045). There were no significant difference in migration of N staging, OS and DFS between two groups. However, for patients with lesions between 2 and 3 cm, the 5-year OS in LA group was significantly higher than that in LS group (81.6 vs. 55.8%, P = 0.041), and the 5-year DFS was also higher (77.9 vs. 52.5%, P = 0.038). For patients with lesions of 2 cm or less, 5-year OS and DFS were similar in both groups. Multivariate analysis showed that lymph node metastasis was the unique unfavorable prognostic factor (P < 0.001).ConclusionsAfter being intraoperatively identified as stage T1, patients with lesions between 2 and 3 cm in cIA NSCLC should be performed with LA to get a potentially better survival, and patients with lesions of 2 cm or less should be performed with LS to decrease invasion.

Upregulation of caspase-3 expression in esophageal cancer correlates with favorable prognosis: an immunohistochemical study from a high incidence area in northern China

Caspase-3 plays an important role as the key effector during apoptosis, but there are very few studies of caspase-3 in esophageal squamous cell carcinoma (ESCC). The purpose of this study was to investigate the expression and prognostic significance of caspase-3 in ESCC from Linzhou City, a high incidence area in northern China. All 64 patients underwent esophagectomy for ESCC between January 2002 and December were enrolled in this study. Caspase-3 expression was assessed by immunohistochemistry (IHC) in primary ESCC and paired normal esophageal epithelium. The positive rate of caspase-3 expression was higher in ESCC than in normal esophageal epithelium (79.7% vs. 50.0%, Chi-square = 12.372, P= 0.001). Caspase-3 expression was correlated with tumor cell differentiation (Phi = 0.717, P < 0.001), tumor infiltration depth (Phi =-0.334, P= 0.008), and pathologic TNM (pTNM) staging (rs =-0.268, P= 0.032). Patients in caspase-3 positive group had a significantly better 5-year overall survival than those in the negative group (77.4% vs. 35.9%, chi(2)= 7.344, P= 0.007). Our results showed that caspase-3 expression was upregulated in ESCC compared with normal esophageal epithelium in population of Chinese high incidence area, and patients with caspase-3 positive expression had better prognosis. Therefore, caspase-3 immunostaining could be a simple and useful tool for predicting survival in ESCC patients.

Expression and Significance of FRA-1 in Non-Small-Cell Lung Cancer

Fra-1 is thought to play an important role in tumorigenesis and progression. This study aimed to investigate the expression and significance of Fra-1 in non-small-cell lung cancer (NSCLC). By analyzing with Western blot and immunohistochemistry, we found that Fra-1 is downregulated in NSCLC, compared with normal bronchial epithelium. Further, the low expression of Fra-1 correlates with advanced tumor stage and poor survival. Meanwhile, the distinct cytoplasmic location of Fra-1 was found in almost all immunoreactive cells. These findings reveal a potential nontranscriptional function of Fra-1, and indicate that Fra-1 might play a role in the progression and prognosis of NSCLC.

New orthotopic implantation model of human esophageal squamous cell carcinoma in athymic nude mice

Subcutaneous xenograft is a common method to establish animal models of human esophageal squamous cell carcinoma (ESCC). However, the growth microenvironment of transplanted tumors is different from primary tumors. Orthotopic implantation models can provide more biologically relevant context in which to study the disease. So far, an orthotopic implantation model of ESCC has rarely been reported.

Expression of cyclooxygenase-2, vascular endothelial growth factor, and epidermal growth factor receptor in Chinese patients with esophageal squamous cell carcinoma.

BACKGROUND Esophageal squamous cell carcinoma (ESCC) is a frequently occurring cancer with poor prognosis despite combined therapeutic strategies. The aim of the current study was to elucidate a further finding on the clinicopathologic significance of immunohistochemical expression of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), and epidermal growth factor receptor (EGFR) in Chinese patients with ESCC. METHODS Formalin-fixed paraffin-embedded surgically resected tumor samples were obtained from 140 randomly selected Chinese patients with ESCC. Sections were immunohistochemically stained for COX-2, VEGF, and EGFR. The correlations between clinicopathological features and the high expression of COX-2, VEGF, and EGFR were analyzed using the Statistical Package for the Social Sciences 19.0 software (IBM Inc., Chicago, IL, USA). RESULTS In the present study, high expression of COX-2, EGFR, and VEGF was found in 64.3%, 62.1%, and 65.0%, respectively. Results showed that COX-2 overexpression was significantly correlated with degree of differentiation (P = 0.000), and lymph node metastasis (negative/positive, P = 0.002). EGFR and VEGF overexpression was significantly correlated with a differentiated degree, T stage, N stage, and tumor, node, metastases stage. CONCLUSION High expression of COX-2, EGFR, and VEGF is an unfavorable prognostic factor in ESCC, and could be used as a poor prognosis indicator for the ESCC patients. Targeting therapy to these three targets should be considered to the combined treatment in ESCC.

Postoperative CYFRA 21-1 and CEA as prognostic factors in patients with stage I pulmonary adenocarcinoma

Background Patients with pathological stage I pulmonary adenocarcinoma have different postoperative prognosis. The aim of this study is to evaluate the prognostic significance of preoperative and postoperative serum levels of carcinoembryonic antigen (CEA) and CYFRA 21-1 in patients with pathological stage I pulmonary adenocarcinoma. Material and Methods We retrospectively reviewed the data of 123 patients who had undergone a complete resection for pathological stage I pulmonary adenocarcinoma between 2004 and 2014. The clinical data of each patient including age, gender, preoperative and postoperative serum CEA and CYFRA 21-1 levels, and pathologic stage, was collected for analysis. Results The CYFRA 21-1 and CEA level was persistently normal in 80.5% and 77.2% of all patients with p-stage I ADC, respectively. The preoperative level was elevated and postoperative level declined to normal for CYFRA 21-1 and CEA were in 10.6% and 13.0% of all patients, respectively. The postoperative CYFRA 21-1 and CEA level were high in 8.9% and 9.8% of all patients, respectively. The postoperative 5-year survival rate of patients with normal, only preoperative high, and postoperative high CYFRA 21-1 level was 92.6%, 92.3% and 43.8%, respectively. There was a significant difference between postoperative high group and the other two groups (p = 0.002). The postoperative 5-year survival rate of patients with normal, only preoperative high, and postoperative high CEA level was 90.8%, 92.3%, and 70.1%, respectively. There was a significant difference between postoperative high group and the other two groups (p = 0.019). In univariate analysis, degree of differentiation, visceral pleural invasion, tumor size, and pTNM stage, was found to be significant independent prognostic factor (p = 0.014). Multivariate analysis showed that pTNM stage, postoperative CYFRA 21-1 high level, and postoperative CEA high level was related to the poor prognosis. Conclusions Patients of p-stage I ADC with postoperative high serum level of either CEA or CYFRA 21-1 had poor prognosis. Carefully followed-up might be necessary to rule out occult metastasis for these patients, and further clinical studies will be necessary to evaluate the efficacy of adjuvant chemotherapy or target therapy. Postoperative high serum level of CEA or CYFRA 21-1 might be a subtype of p-stage I ADC.BACKGROUND Patients with pathological stage I pulmonary adenocarcinoma have different postoperative prognosis. The aim of this study is to evaluate the prognostic significance of preoperative and postoperative serum levels of carcinoembryonic antigen (CEA) and CYFRA 21-1 in patients with pathological stage I pulmonary adenocarcinoma. MATERIAL AND METHODS We retrospectively reviewed the data of 123 patients who had undergone a complete resection for pathological stage I pulmonary adenocarcinoma between 2004 and 2014. The clinical data of each patient including age, gender, preoperative and postoperative serum CEA and CYFRA 21-1 levels, and pathologic stage, was collected for analysis. RESULTS The CYFRA 21-1 and CEA level was persistently normal in 80.5% and 77.2% of all patients with p-stage I ADC, respectively. The preoperative level was elevated and postoperative level declined to normal for CYFRA 21-1 and CEA were in 10.6% and 13.0% of all patients, respectively. The postoperative CYFRA 21-1 and CEA level were high in 8.9% and 9.8% of all patients, respectively. The postoperative 5-year survival rate of patients with normal, only preoperative high, and postoperative high CYFRA 21-1 level was 92.6%, 92.3% and 43.8%, respectively. There was a significant difference between postoperative high group and the other two groups (p = 0.002). The postoperative 5-year survival rate of patients with normal, only preoperative high, and postoperative high CEA level was 90.8%, 92.3%, and 70.1%, respectively. There was a significant difference between postoperative high group and the other two groups (p = 0.019). In univariate analysis, degree of differentiation, visceral pleural invasion, tumor size, and pTNM stage, was found to be significant independent prognostic factor (p = 0.014). Multivariate analysis showed that pTNM stage, postoperative CYFRA 21-1 high level, and postoperative CEA high level was related to the poor prognosis. CONCLUSIONS Patients of p-stage I ADC with postoperative high serum level of either CEA or CYFRA 21-1 had poor prognosis. Carefully followed-up might be necessary to rule out occult metastasis for these patients, and further clinical studies will be necessary to evaluate the efficacy of adjuvant chemotherapy or target therapy. Postoperative high serum level of CEA or CYFRA 21-1 might be a subtype of p-stage I ADC.

Experimental reconstruction of cervical esophageal defect with artificial esophagus made of polyurethane in a dog model

The defect of esophagus after surgical excision in patients is usually replaced by autologous stomach, jejunum, or colon. The operation brings severe trauma and complications. Using artificial esophagus to replace the defect in situ can reduce the operative trauma, simplify the operative procedures, and decrease the influence to digestive function. A variety of experiments have been designed for developing a practical artificial esophagus. Nevertheless, a safe and reliable artificial esophagus is not yet available. The objective is to evaluate the possibility of the artificial esophagus made of non-degradable polyurethane materials being used in reconstruction of the segmental defect of cervical esophagus in beagles, observe the regeneration of esophageal tissue, and gather experience for future study. The cervical esophageal defects in 13 beagles were designed to 2-cm long and were constructed by the artificial esophagus made of non-degradable polyurethane materials. Nutrition supports were given after the operation. The operative mortality, anastomotic leakage, migration of artificial esophagus, and dysphagia were followed up. The regeneration of the esophageal tissues was evaluated by histopathology and immunohistochemical labeled streptavidin-biotin method. The surgical procedures were successfully completed in all beagles, and 12-month follow-ups were done. Only one beagle died of severe infection, and all others survived until being killed. The anastomotic leakage occurred in nine beagles, most of them (8/9) were cured after supportive therapy. The migration of artificial esophagus occurred in all 12 surviving beagles, and one artificial esophagus stayed in situ after migration. All 12 surviving beagles showed dysphagia with taking only fluid or soft food. No beagle died of malnutrition. The neo-esophagus was composed of granulation tissue, and the inner surface was covered by epithelium in 2-3 months completely. But the inner surface of neo-esophagus with artificial esophagus staying in situ after migration was not covered by epithelium, and the granulation tissue was infiltrated by a great deal of inflammatory cells. Antibodies against cytokeratin were positively expressed in epithelium of neo-esophagus. Up to 12 months after operation, antibodies against smooth muscle actin and desmin were both negatively expressed in neo-esophagus. The artificial esophagus made of non-degradable polyurethane reconstructing cervical esophageal defect is practicable. Although there are some problems, including anastomotic leakage, migration, and dysphagia, they are not lethal following good supportive therapy. The esophageal epithelium can regenerate with the supporting role of artificial esophagus. In the future, deformable artificial esophagus should be improved, and a much longer follow-up will be performed to evaluate whether the esophageal gland and skeletal muscle can regenerate.

High preoperative and postoperative levels of carcinoembryonic antigen and CYFRA 21-1 indicate poor prognosis in patients with pathological Stage I nonsmall cell lung cancer

BACKGROUND Serum carcinoembryonic antigen (CEA) and the soluble fragment of cytokeratin 19 (CYFRA 21-1) are supposed to have a prognostic role in patients with nonsmall cell lung cancer (NSCLC) after surgery, but it has not been used as an adjunct to the tumor-node-metastasis (TNM) staging system to provide therapy options for patients with pathological Stage I NSCLC. This study was designed to investigate the effect of serum levels of CEA and CYFRA 21-1 before and after surgery on the prognosis of patients with Stage I NSCLC. MATERIALS AND METHODS A retrospective review was performed regarding the medical records and follow-ups of 169 patients with Stage I NSCLC before and after surgery. The patients were divided into three groups based on levels of serum CEA and CYFRA 21-1 before and after surgery: (1) continuously normal-level groups (CEA [NN] and CYFRA 21-1 [NN] groups); (2) declined to normal-level groups (CEA [HN] and CYFRA 21-1 [HN] groups); and (3) continuously high-level groups (CEA [HH] and CYFRA 21-1 [HH] groups). Survival analysis was conducted using the Kaplan-Meier method for each group. The Chi-square or Fisher exact test was employed to compare clinical and pathologic factors at the level of P < 0.05. The prognostic factor was evaluated by the Cox proportional hazards model. RESULTS Compared with the continuously normal-level groups, the CEA [HN] group was significantly correlated to tumor size (P = 0.011), and the CYFRA 21-1 [HN] group was significantly correlated to tumor type and pathological TNM in addition to tumor size. Five-year survivals were significantly lower (P = 0.004) in the CEA [HH] group (67.3%) and the CEA [HN] group (86.5%) than in the CEA [NN] group (85.7%) and were significantly lower (P < 0.001) in the CYFRA 21-1 [HH] group (47.2%) and the CYFRA 21-1 [HN] group (70.1%) than in the CYFRA 21-1 [NN] group (90.1%). Multivariate analysis demonstrated that tumor size (21-50 mm), CEA [HH], and CYFRA 21-1 [HH] were independent unfavorable prognostic factors for overall survival (OS), whereas tumor size (21-50 mm), CEA [HH], CYFRA 21-1 [HN], and CYFRA 21-1 [HH] were independent significant prognostic factors for progression-free survival (PFS). CONCLUSION Patients with a persistently high serum CEA or CYFRA 21-1 before and after surgery had shortest OS and PFS. These patients had worst prognosis. Adjuvant chemotherapy was likely to improve survival for these patients.