Clinicopathological Variation of Lauren Classification in Gastric Cancer.

The investigation of prognostic factor for gastric cancer is still desirable because of dismal prognosis in gastric cancer. Lauren's classification is currently a useful histological classification. There are few large series evaluating the prognostic significance of Lauren's classification in gastric cancer. From January 1987 to December 2013, a total of 3071 patients received gastrectomy for gastric cancer. According Lauren's classification, 1423(46.3%) patients were intestinal type, 1000 patients (32.6%) were diffuse type, and 648 patients (21.1%) were mixed type. The clinicopathological characteristics and prognosis in Lauren's classification were analyzed in these patients. Our results showed that patients with intestinal type gastric cancer (57.7%) had a better 5-year overall survival than diffuse type (45.6%) and mixed type (43.4%, P < 0.001). The clinicopathological characteristics showed that gastric cancer patients with intestinal type were older (P < 0.001), male predominant (P < 0.001), smaller tumor size (P < 0.001), distal stomach predominant (P < 0.001), relative well differentiated (P < 0.001), less advanced Borrmann type (P < 0.001), less scirrhous type stromal reaction(P < 0.001), less infiltrating type of Ming's histology type(P < 0.001), less tumor invasion depth and less lymphovascular invasion (P < 0.001). Multivariate analysis with overall survival as an endpoint showed that age (P = 0.005), Borrmann classification (P < 0.001), pathological T category (P = 0.023), pathological N category (P < 0.001) and Lauren's classification (P = 0.003) were significant correlated in gastric cancer. Lauren's classification is an independent prognostic factor in gastric cancer patient undergoing gastrectomy. Lauren's classification can serve as a prognostic marker for gastric cancer patient receiving gastrectomy. The clinicopathological appearance and prognosis of mixed type gastric cancer is similar to diffuse type gastric cancer.

Identification of alpha-enolase as an autoantigen in lung cancer: its overexpression is associated with clinical outcomes.

PURPOSE: Although existence of humoral immunity has been previously shown in malignant pleural effusions, only a limited number of immunogenic tumor-associated antigens (TAA) have been identified and associated with lung cancer. In this study, we intended to identify more TAAs in pleural effusion-derived tumor cells. EXPERIMENTAL DESIGN: Using morphologically normal lung tissues as a control lysate in Western blotting analyses, 54 tumor samples were screened with autologous effusion antibodies. Biochemical purification and mass spectrometric identification of TAAs were done using established effusion tumor cell lines as antigen sources. We identified a p48 antigen as alpha-enolase (ENO1). Semiquantitative immunohistochemistry was used to evaluate expression status of ENO1 in the tissue samples of 80 patients with non-small cell lung cancer (NSCLC) and then correlated with clinical variables. RESULTS: Using ENO1-specifc antiserum, up-regulation of ENO1 expression in effusion tumor cells from 11 of 17 patients was clearly observed compared with human normal lung primary epithelial and non-cancer-associated effusion cells. Immunohistochemical studies consistently showed high level of ENO1 expression in all the tumors we have examined thus far. Log-rank and Cox's analyses of ENO1 expression status revealed that its expression level in primary tumors was a key factor contributing to overall- and progression-free survivals of patients (P < 0.05). The same result was also obtained in the early stage of NSCLC patients, showing that tumors expressing relatively higher ENO1 level were tightly correlated with poorer survival outcomes. CONCLUSIONS: Our data strongly support a prognostic role of ENO1 in determining tumor malignancy of patients with NSCLC.

Expression of c-kit, Flk-1, and Flk-2 receptors in benign and malignant tumors of follicular epithelial origin.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a key regulator of physiologic as well as pathologic angiogenesis. The response of VEGF to endothelial cell mitogenesis and survival, as well as angiogenesis and microvascular permeability, is mainly mediated through its receptor-2, VEGFR2 (kinase domain receptor or fetal liver kinase-1, KDR or Flk-1). This study aimed to detect the expression of VEGFR2 in various forms of thyroid tumors. In addition, the expression of Flk-2 (receptor for Flt-3) and c-Kit (receptor for steel locus factor), which shows strong similarity to Flk-1, was also examined in thyroid tumors. METHODS: RT-PCR analyses of c-Kit and immunohistochemical staining of c-Kit, Flk-1, and Flk-2 were performed in archived samples of 18 papillary thyroid carcinoma (PTC), 9 follicular thyroid carcinoma (FTC), 12 follicular adenoma (FA), and 7 nodular goiter (NG) samples. The data were correlated to clinicopathologic features. RESULTS: By RT-PCR analyses, c-Kit expression was detected in 22% (4/18) of PTC, 22% (2/9) of FTC, 25% (3/12) of FA, and 57% (4/7) of NG samples. However, positive immunostaining signals of c-Kit were only observed in 17% (3/18) of PTC samples, and not in the others. Similarly, Flk-1 expression was only detected by immunohistochemistry in 67% (12/18) of PTC and 43% (3/7) of NG samples, and not in the others. Interestingly, the expression of Flk-2 was found in 89% (16/18) of PTC, 89% (8/9) of FTC, 75% (9/12) of FA, and 29% (2/7) of NG samples. An inverse relationship of thyroid cancer size with Flk-2 expression was found. CONCLUSION: Flk-2 expression was detected in various forms of thyroid tumors and increased Flk-2 expression was correlated with thyroid tumors with increased transforming activity, suggesting that Flk-2 is involved in pathogenic development of thyroid malignancy. Similarly, Flk-1 expression was also found in some thyroid tumors, while the expression of c-Kit-mediated pathways may not play a major role in thyroid tumorigenesis.

Prognostic implications of the expression of erbB2, topoisomerase II alpha and thymidylate synthase in metastatic gastric cancer after fluorouracil-based therapy.

OBJECTIVE: This retrospective study aimed to ascertain the expression of erbB2 in relation to topoisomerase II alpha (T2 alpha) and thymidylate synthase (TS) markers in 30 consecutive metastatic gastric cancer patients with a specimen available for study. METHODS: All patients had been entered on consecutive chemotherapeutic clinical trials that were all 5-fluorouracil based. The specimens were evaluated by fluorescence in situ hybridization to ascertain erbB2 and T2 alpha gene amplification, and by immunohistochemical staining for T2 alpha and TS protein expression. RESULTS: erbB2 amplification was detected in 16.7% of specimens, with co-amplification of the T2 alpha gene in 40%, and 44% had undetectable TS protein expression. Kaplan-Meier survival curves showed significantly prolonged overall survival in patients with erbB2 and T2 alpha gene amplification, T2 alpha protein overexpression and absence of TS protein expression (P = 0.0011, P = 0.0048, P = 0.0061 and P = 0.0267, respectively, by log rank test). There was a positive correlation between erbB2 amplification and T2 alpha amplification, T2 alpha protein overexpression, and a trend towards absence of TS expression (P = 0.0001, P = 0.003 and P = 0.066 by Fisher's exact test). CONCLUSION: High dose fluorouracil/leucovorin-based chemotherapy may have the potential to reverse the adverse effects resulting from erbB2 gene amplification in gastric cancer.

Peritoneal carcinomatosis and lymph node metastasis are prognostic indicators in patients with Borrmann type IV gastric carcinoma.

BACKGROUND/AIMS: Having observed a lower survival rate of patients with Borrmann type IV gastric cancer, we attempted to determine its prognostic indicators. METHODOLOGY: A total of 103 patients with Borrmann type IV gastric cancer were evaluated; 604 patients with Borrmann types I, II and III were used as references. RESULTS: The results showed that Borrmann type IV gastric cancer were larger, had deeper invasion, more lymphatic and vascular invasions, predominant diffuse type and scirrhous stromal reaction, extensive lymph node metastases and peritoneal carcinomatosis. The 5-year survival rate (11.3%) was significantly lower than that of others (44.7%, P < 0.001). Univariate and multivariate analyses of survival showed that peritoneal carcinomatosis and lymph node metastasis were independently associated with a relative risk of 1.8 and 1.4, respectively. The survival rates of 46 patients with potential curative disease were similar, regardless of various extents of resection. CONCLUSIONS: Peritoneal carcinomatosis and lymph node metastases are prognostic indicators in patients with Borrmann type IV gastric cancer. Optimal surgical strategy for Borrmann type IV gastric cancer remains unclear.

Phase II and pharmacokinetic study of GL331 in previously treated Chinese gastric cancer patients.

PURPOSE: A phase II and pharmacokinetic study was designed to assess the efficacy and toxicity profile of an epidophyllotoxin analogue, GL331, in previously treated Chinese gastric cancer patients, with concurrent pharmacokinetic evaluation of the drug's metabolism. MATERIAL AND METHODS: GL331 was given at 200 mg/m(2) as a daily 3-h infusion for 5 days every 4 weeks. RESULTS: Enrolled in the study were 15 patients. One patient died from neutropenic sepsis before evaluation, one patient did not receive the full dose for reasons unrelated to GL331, nine patients had progressive disease with a median survival of 80 days, and five had stable disease with a median survival of 240 days. Grade 3 and 4 myelosuppression occurred in 10 of the 15 patients, with one death from neutropenic sepsis. This patient's peak GL331 concentration was 16.8 microg/ml, which was high compared to the mean peak drug concentration of 6+/-4.1 microg/ml. The mean systemic GL331 clearance was 12.1+/-7.2 l/h per m(2), much lower than 23.3+/-8.2 l/h per m(2) found in the phase I trial. Topoisomerase IIalpha was determined by immunohistochemistry and overexpression was detected in 3 of 11 specimens. CONCLUSIONS: GL331 was ineffective at this dose and schedule in this group of patients in spite of adequate blood levels of the drug.