Hongyu Gao

Clinicopathologic Features of Gastric Carcinoma with Signet Ring Cell Histology

BackgroundReports of clinicopathological features and prognosis in patients with signet ring cell carcinoma of the stomach (SRC) are conflicting. The aim was to describe the clinicopathological features and prognosis of patients with SRC in comparison with non-signet ring cell carcinoma of the stomach (NSRC).MethodsIn this retrospective study, we reviewed the records of 1,439 consecutive patients diagnosed with gastric carcinoma who were resected surgically from 1993 to 2003. Among them, 218 patients (15.1%) with SRC were compared with 1,221 patients with NSRC.ResultsThere were significant differences in tumor size, tumor location, macroscopic type, depth on invasion, lymph node metastasis, lymphatic invasion, tumor stage, chemotherapy, and curability between the patients with SRC histology and NSRC. The overall 5-year survival of patients with SRC was 44.9% as compared with 36.0% for patients with NSRC (P = 0.013). Multivariate analysis showed that lymph node metastasis and curative resection were significant factors affecting survival. A significant survival benefit for curative resection was observed, with a 5-year survival rate of 58.5% compared with non-curatively resected cases (8.4%).ConclusionsWhen stage matched, SRC patients had a similar survival to NSRC patients. Curative resection is recommended to improve the prognosis of patients with SRC.

Expression of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in gastric adenocarcinoma

Matrix metalloproteinases (MMPs) are one of the major classes of proteolytic enzymes involved in tumor invasion and metastasis, being inhibited by naturally occurring tissue inhibitors of metalloproteinases (TIMPs). We examined mRNA expression for MMP‐2, MMP‐7, MMP‐9, MT1‐MMP, TIMP‐1, and TIMP‐2 in human gastric adenocarcinoma tissues, and the correlation between their expression and clinicopathological variables.

Clinicopathologic characteristics and prognosis of mucinous gastric carcinoma.

Reports of clinicopathological features and prognosis in patients with mucinous gastric carcinoma (MGC) are conflicting. The aim was to describe the clinicopathological features and prognosis of patients with MGC in comparison with nonmucinous gastric carcinoma (NMGC).

Derived neutrophil to lymphocyte ratio and monocyte to lymphocyte ratio may be better biomarkers for predicting overall survival of patients with advanced gastric cancer

Background and objectives Preoperative systemic inflammatory response and nutritional status play important roles in the tumorigenesis, progression, and prognosis of gastric cancer (GC). This research is designed to investigate the prognostic value of the biomarkers including the neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), and prognostic nutritional index (PNI) in predicting overall survival in patients with GC. Methods A total of 1,990 consecutive GC patients who underwent gastrectomy from 2007 to 2011 were enrolled and divided into high level and low level based on the optimal cut-off points for NLR, dNLR, MLR, PLR, and PNI, respectively. The clinicopathological characteristics of the two levels were comparatively analyzed. Overall survival analysis was executed using these biomarkers and clinicopathological characteristics. Results The number of metastatic lymph nodes, distant metastasis, American Joint Committee on Cancer TNM stage, radicality, tumor size, metastatic lymph nodes ratio, ascites, and Hb were all significantly associated with NLR, dNLR, MLR, PLR, and PNI. All of these five biomarkers were closely associated with overall survival in univariate analyses, but only dNLR and MLR were significant in multivariate model. dNLR and MLR can be bonded to predict survival, but whether separate or together, dNLR and MLR were mainly significant in advanced stages. Conclusion Although preoperative NLR, dNLR, MLR, PLR, and PNI in peripheral blood proved significant prediction of prognoses of postoperative GC patients, dNLR and MLR may be better biomarkers for predicting overall survival, especially in advanced GC patients.

Relationships of MMP-9, E-cadherin, and VEGF expression with clinicopathological features and response to chemosensitivity in gastric cancer

The matrix metalloproteinase-9, E-cadherin, and vascular endothelial growth factor play an important role in behavior of tumor cell growth, invasion, and metastasis. In this study, we investigated the relationships of matrix metalloproteinase-9, E-cadherin, and vascular endothelial growth factor expression with clinicopathological features and results of chemosensitivity tested by collagen gel droplet–embedded culture–drug sensitivity test in gastric cancer. Fresh specimens were used for collagen gel droplet–embedded culture–drug sensitivity test and paired fixed specimens were used for immunohistochemistry. Positive expression of matrix metalloproteinase-9 was associated with poorly differentiated carcinoma (p = 0.032), lymph node metastasis (p = 0.022), and tumor stage (p = 0.023). Negative expression of E-cadherin was associated with poorly differentiated carcinoma (p = 0.007), lymph node metastasis (p = 0.012), and tumor stage (p = 0.007). Positive expression of vascular endothelial growth factor was associated with tumor size (p = 0.040) and stage (p = 0.007). Collagen gel droplet–embedded culture–drug sensitivity test was successfully evaluated in 56 patients. Among them, 29 (51.7%) patients were resistant to TS-1 and 31 (55.3%) patients were resistant to L-OHP. The L-OHP resistance rate in vascular endothelial growth factor positive patients was significantly higher than that in negative patients (p = 0.031). The L-OHP resistance rate in E-cadherin negative patients was significantly higher than that in positive patients (p = 0.014). In conclusion, matrix metalloproteinase-9, E-cadherin, and vascular endothelial growth factor were involved in tumor invasion and metastasis. Positive expression of matrix metalloproteinase-9 and vascular endothelial growth factor and negative expression of E-cadherin were malignant markers for gastric cancer. Positive expression of vascular endothelial growth factor and negative expression of E-cadherin were associated with L-OHP resistance.

Increased BTLA and HVEM in gastric cancer are associated with progression and poor prognosis

Purpose Deregulation of immune checkpoint molecules by tumor cells is related to immune escape. This study was conducted to investigate the relationship between the appearance of B- and T-lymphocyte attenuator (BTLA) and its ligand herpesvirus entry mediator (HVEM) with the prognosis in gastric cancer patients. Patients and methods A total of 136 patients with curative gastrectomy were included. The expression of BTLA and HVEM was detected by immunohistochemistry, and its correlation with the clinical significance of gastric cancer was further analyzed. Results The positivity of BTLA and HVEM was detected in 74.3% (101/136) and 89.0% (121/136) of the gastric cancer specimens, respectively. A high expression of BTLA and HVEM was detected, respectively, in 28.7% (39/136) and 44.9% (61/136) of the specimens. Characteristics analysis showed that the high expression of BTLA was significantly associated with lymph node metastasis (P=0.030). Similarly, the high expression of HVEM was also significantly correlated with lymph node metastasis (P=0.007) and depth of invasion (P=0.011). In addition, there was a positive correlation between the expression of BTLA and HVEM in gastric cancer specimens (r=0.245, P=0.004). Univariate analysis revealed that the high expression of BTLA and HVEM was associated with overall survival of patients along with tumor size, Borrmann type, depth of invasion, lymph node metastasis, and histological grade (P<0.05). Multivariate analysis established that the high expression of HVEM (P=0.010), depth of invasion (P=0.001), lymph node metastasis (P<0.001), and histological grade (P=0.027) were independent prognostic factors associated with overall survival in patients with gastric cancer. Conclusion The increased BTLA and HVEM levels correlate with the development and poor prognosis of gastric cancer. HVEM is an important prognostic indicator, and BTLA/HVEM pathway is considered to be a promising candidate for immunotherapy of gastric cancer.

Elevated HABP1 protein expression correlates with progression and poor survival in patients with gastric cancer

Background Hyaluronic acid-binding protein 1 (HABP1/gC1qR/p32) has been recently implicated in oncogenesis and cancer progression in various malignancies; however, its clinical role in gastric cancer (GC) is still unclear. Patients and methods First, HABP1 expression was determined by Western blot analysis and immunohistochemistry. Then, we evaluated the expression of HABP1 and its clinical significance in tumor tissues from 181 patients with GC. Results Expression of HABP1 protein in GC tissues was noticeably higher than that in adjacent nonneoplastic tissues (P=0.018). Increased HABP1 expression was significantly associated with tumor, node, and metastasis (TNM) stage (P=0.006), depth of invasion (P=0.001), lymph node metastasis (P=0.001), liver metastasis (P=0.024), and peritoneum metastasis (P=0.009). Patients with high expression of HABP1 had poor overall survival rate (P<0.001). In addition, histologic grade (P=0.017), TNM stage (P<0.001), Borrmann grouping (P<0.001), depth of invasion (P<0.001), lymph node metastasis (P<0.001), liver metastasis (P=0.010), and tumor size (P<0.001) were independent prognostic factors for overall survival. Multivariate Cox regression analysis revealed that HABP1 (P=0.004), histologic grade (P=0.047), TNM stage (P<0.001), Borrmann grouping (P<0.001), and liver metastasis (P=0.038) were independent factors for overall survival in patients with GC. Conclusion These findings demonstrated that HABP1 was an indicator for GC progression and poor survival, which highlighted its potential role as a therapeutic target for GCs.

Addition of peritonectomy to gastrectomy can predict good prognosis of gastric adenocarcinoma patients with intraoperatively proven single P1/P2 carcinomatosis

This study was to evaluate the prognosis of peritonectomy following gastrectomy for gastric adenocarcinoma patients with intraoperatively proven single P1/P2 carcinomatosis and to define the best therapeutic strategy of the patient cohort. The patients with intraoperatively proven single P1/P2 carcinomatosis from a prospectively maintained database were divided into resection group and non-resection group based on complete gross resection of peritoneal carcinomatosis. From 2005 to 2012, there were 103 patients in the resection group and 122 patients in the non-resection group. There was no difference in morbidity and mortality between groups. The patients did not have improved median survival in P1 carcinomatosis compared to P2 carcinomatosis (15.53 vs 14.80 months, p = 0.450). The median survival was significantly improved in the resection group compared to the patients in the non-resection group (21.07 vs 13.37 months, p < 0.001). The patients undergoing complete gross peritonectomy plus postoperative chemotherapy had a significantly longer median survival than patients who had complete gross peritonectomy alone, patients receiving postoperative chemotherapy alone, and patients receiving neither peritonectomy nor postoperative chemotherapy (27.33 vs 12.00 vs 16.00 vs 10.33 months, p < 0.001). In the multivariate analysis, poor performance status (p = 0.036), absence of complete gross peritonectomy (p < 0.001), and lack of postoperative chemotherapy (p < 0.001) were identified as independently associated with poor survival. The data indicate complete gross peritonectomy following gastrectomy confers a survival benefit to gastric cancer patients with intraoperatively proven single P1/P2 carcinomatosis. In addition, postoperative chemotherapy improves survival regardless of resection of peritoneal carcinomatosis and should be recommended.