[Significance of expression of chemokine receptor and matrix metalloproteinase in small cell lung cancer].

OBJECTIVE: To explore the expressions of CXC chemokine receptor 4 (CXCR4) and matrix metalloproteinase-9 (MMP-9) and examine their correlations with metastasis and prognosis in small cell lung cancer (SCLC). METHODS: Immunohistochemistry was employed to detect the expressions of CXCR4 and MMP-9 in the tissue samples from 65 SCLC patients treated in Cancer Institute and Hospital Attached to Tianjin Medical University from January 2003 to October 2009. And their correlations with metastasis and prognosis were analyzed by Chi-square test and Kaplan-Meier method and Cox regression. RESULTS: The positive expression rates of CXCR4 and MMP-9 were 100.0% (65/65) and 87.7% (57/65) in SCLC tissues respectively. Significant difference of the expression rate of CXCR4 was found between patients undergoing bone metastasis or not (P = 0.004). But the differences were not significant between brain metastasis or not (P = 0.068) and lymph node metastasis or not (P = 0.085). A high expression rate of MMP-9 was significantly associated with pathological staging (P = 0.048). But the difference between lymph node metastasis or not was not significant (P = 0.085). Univariate analysis suggested that a high expression rate of CXCR4 was significantly correlated with the disease-free survival (DFS) of SCLC patients (P = 0.005). But a high expression rate of MMP-9 was not associated with DFS (P = 0.341). Multivariate analysis suggested that a high expression rate of CXCR4 was an independent prognostic factor for DFS in SCLC. CONCLUSIONS: The elevated levels of CXCR4 and MMP-9 are found in SCLC tissues. And the expression rate of CXCR4 may be correlated with bone metastasis, but the correlation is not notable for MMP-9. The expression rate of CXCR4 is an independent prognostic factor for DFS in SCLC.

Different sites and prognoses of gastrointestinal stromal tumors of the stomach: report of 187 cases.

BACKGROUND: The stomach is the most common site of gastrointestinal stromal tumors (GISTs), but the clinical behavior of gastric GISTs at different sites is unclear. This study was designed to evaluate the clinicopathological (CP) parameters and influence of different gastric sites on outcome in patients with GIST. METHODS: The CP and follow-up records of 187 patients with GIST who were treated at TianJin Medical University Cancer Institute & Hospital between January 1985 and December 2006 were reviewed. There were 97 men and 90 women (aged 17-88 (median, 56.5) years). CP factors were assessed for overall survival (OS) by using univariate and multivariate analysis. RESULTS: The numbers of cases of upper, middle, and lower third gastric GISTs were 69 (36.9%), 103 (55.1%), and 15 (8%), respectively. Sites of GISTs in the middle or upper stomach, tumor size, intermediate- or high-risk groups, high mitotic count, and low resection status were associated with poor OS (p = 0.041, 0.046, 0.006, 0.000, 0.000, respectively) in a univariate analysis. In a multivariate analysis, tumor location in the upper and middle third of the stomach (p = 0.035), an intermediate or high risk (p = 0.01), and incomplete resection status (p = 0.006) were predictive of poor OS. CONCLUSIONS: Patients in intermediate- and high-risk groups had an unfavorable outcome. A complete resection is the most important treatment for survival. The location of GIST in the lower third of the stomach may be a favorable factor, and the significance of different tumor sites for prognosis of gastric GISTs needs to be further clarified.

[Relationship between EGFR and K-ras mutations and clinicopathological characteristics and response to erlotinib treatment in 301 Chinese patients with non-small cell lung cancer].

OBJECTIVE: To investigate gene mutations of epidermal growth factor receptor (EGFR) and K-ras in Chinese patients with non-small cell lung cancer (NSCLC) and its clinicopathological significance, and to analyze the correlation between these mutations and tumor response to erlotinib treatment. METHODS: Mutations of exons 18, 19, 20 and 21 of the EGFR and codons 12, 13 of the K-ras in 301 cases of NSCLC were detected by PCR-amplification and gene sequencing. The relationship between the mutations and clinicopathological characteristics of the 301 patients was analyzed. RESULTS: EGFR mutations were present in 32.9% (99/301) of the samples: 3 mutation in exon 18, 59 in exon 19, 2 in exon 20, and 35 in exon 21. Mutations of K-ras were present in 4.7% (14/301) of the samples: 13 in codon 12 and 1 in codon 13. EGFR mutations were never found in tumors with K-ras mutations, suggesting a mutually exclusive relationship. EGFR mutations were more common in adenocarcinomas, non-smokers and females. Seven out of 10 erlotinib-treated patients with disease control carried EGFR mutation. CONCLUSION: The frequency of EGFR mutation in Chinese NSCLC patients is higher than that in Westerners, but the frequency of K-ras mutation is quite opposite. Combined detection of EGFR gene and K-ras gene mutation may help clinicians to choose patients who may gain benefit from EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment, and to predict their response to erlotinib treatment and prognosis.

[Expression of coxsackievirus and adenovirus receptor in non-small cell lung cancer and its significance].

OBJECTIVE: To investigate the mRNA and proten expression of coxsackievirus and adenovirus receptor (CAR) in the corresponding normal lung tissue, para-neoplastic tissue and lung cancer tissue, and the correlation of CAR expression with the carcinogenesis as well as the expression difference in various clinicopathologic parameters. METHODS: The expression of CAR mRNA and protein in the samples from 32 lung cancer patients was determined by RT-PCR and Western blot, respectively. RESULTS: The expression level of CAR mRNA and protein in normal lung tissue, paraneoplastic tissue and cancer tissue were 1.000 +/- 0.012, 1.048 +/- 0.035, 1.282 +/- 0.072, and 0.902 +/- 0.038, 0.944 +/- 0.042, 1.08 +/- 0.052, respectively, with a statistical significance among the groups (P = 0.022, P = 0.007, P = 0.009, P = 0.027). There was a statistically significant positive correlation between expression of CAR mRNA and that of CAR protein (r = 0.448, P = 0.026). The expression levels of CAR were significantly different among different pathological types (P = 0.012), with a high level of CAR in all 7 bronchiolo-alveolar carcinoma (BAC, P = 0.029). However, there was no statistical significance in other clinicopathologic parameters (P > 0.05), including gender, age, smoking or not, tumor size, with or without lymph node metastasis and TNM stage. CONCLUSION: The expression of CAR mRNA and protein in cancer tissue samples are significantly higher than that in the normal and paraneoplastic samples, indicating that CAR might play a crucial role in the carcinogenesis. It may become a new potential prognostic marker for lung cancer patients.

[Biological effect of endostatin on transplanted human lung adenocarcinoma Calu-6 tumor in nude mice].

OBJECTIVE: To assess the effect of endostatin on growth and neoplastic angiogenesis in transplanted human lung adenocarcinoma Calu-6 tumor in nude mice. METHODS: To treat Calu-6 tumor-bearing mice with endostatin at different doses, and to record the changes of the tumor size. The expressions of survivin, VEGF, COX-2 and MVD in tumor tissue were examined by immunohistochemistry staining, circulating endothelial cells (CECs) by flow cytometry and mRNA of CD146 and CD105 by RT-PCR and real-time PCR. RESULTS: After endostatin treatment, the tumor size was conspicuously shrunk, and the expressions of survivin, COX-2 and VEGF protein and MVD in tumor tissue decreased concomitantly with the significant difference between each of trial groups and control group (all P < 0.05). Both CECs and mRNA of CD146 and CD105 diminished remarkably. A positive correlation between both exhibition and change of amount of activated CECs and survivin, VEGF expression and MVD count in tumor tissue was found. CONCLUSION: Endostatin can decrease the expression of survivin, COX-2, VEGF and MVD, and to inhibit the growth of transplanted tumor. Activated CECs may probably serve as an ideal marker to predict the efficacy and prognosis of anti-angiogenesis therapy.

[Value of thyroid transcription factor-1 in identification of the prognosis of bronchioloalveolar carcinoma].

OBJECTIVE: To study the expression and clinical significance of cytokeratin subtypes CK7 and CK20 and thyroid transcription factor-1 (TTF-1) in bronchioloalveolar carcinoma (BAC), and to investigate the value of these factors in identification of the prognosis of BAC. METHODS: Eighty-one specimens of BAC resected during operation, 68 of non-mucinous type and 13 of mucinous type, underwent immunohistochemical examination to detect the expression of CK7, CK20, and TTF-1. The value of these 3 factors in the identification of the prognosis of BAC was examined by survival analysis. RESULTS: All specimens showed positive expression of CK7, CK20, and TTF-1. There was no significant differences in CK7 expression rate among different ages, clinical stages, and pathological subtypes (all P > 0.05). Compared with that in the BAC of stage III and that of BAC of non-mucinous type, the CK20 positive rates of the BAC of stage I - II and mucinous type were both significantly higher (chi(2) = 3.928, P < 0.05, and chi(2) = 11.512, P < 0.05). The TTF-1 positive rates of the BAC of stage III and nonmucinous type were significantly higher than those of stage I - II and mucinous type respectively (chi(2) = 7.840, P < 0.05, and chi(2) = 19.497, P < 0.05). There was a statistically significant positive correlation between the expression of CK7 and expression of TTF-1 (r = 0.257, P = 0.021). Univariate analysis showed that the main prognostic factors were TTF-1 expression (P = 0.017), clinical stage (P = 0.000), tumor diameter (P = 0.017) and N stage (P = 0.000). Strata analysis suggested that in the nonmucinous type BAC patients the survival time of those positive for TTF-1 expression was superior to those negative for TTF-1 (P = 0.009); and in the stage III BAC patients the survival time of those positive for TTF-1 was superior to those negative for TTF-1 (P = 0.022). Cox regression analysis suggested that TTF-1 (P = 0.035), TNM stage (P = 0.000), tumor diameter (P = 0.034), and N stage (P = 0.000) were independent factors affecting the prognosis. CONCLUSION: There is a statistically significant positive correlation between the expression of CK7 and the expression of TTF-1. TTF-1 and CK20 provide a new evidence for the molecular staging of BAC. TTF-1, TNM stage, tumor diameter and N stage are all independent factors affecting the prognosis of BAC.

[Diagnosis and treatment of gastrointestinal stromal tumors: a study of 96 patients].

OBJECTIVE: To investigate the pathological diagnosis, surgical treatment and prognostic factors of gastrointestinal stromal tumors (GISTs). METHODS: The clinicopathological data of operated 96 patients with GISTs were analyzed retrospectively. Expression of CD117, CD34, SMA and S-100 was determined by immunohistochemical methods. RESULTS: Expression of CD117, CD34, SMA and S-100 was 79.2% (76/96), 58.3% (56/96), 35.4% (34/96) and 9.4% (9/96). Benign tumor 23 and malignant 73. Of the malignant, the omentum was resected in 39 and the rest remained, of which the recurrent and metastatic rates were 5.1% and 26.5% (P < 0.05). The safety margin between the normal intestine and tumor was > 5 cm in 46 patients; while in the other 27 patients, it was < 5 cm. The recurrent and metastatic rates were 6.5% and 29.6% (P < 0.05), respectively. The 5-year survival rates of benign and malignant GISTs were 91.5% and 57.3% (P < 0.05). CONCLUSION: The application of immunohistochemical markers CD117 and CD34 are supplementary to pathological diagnosis. The adapting of rational primary treatment, including complete tumor resection and prophylactic omentectomy, is able to reduce the recurrence of GISTs.

[Preliminary research on the effect of antisense oligodeoxynucleotides of tankyrase 1 on tumor growth following intratumoral injection in mice].

OBJECTIVE: To observe the suppressing effect of antisense oligodeoxynucleotides of tankyrase 1 (TANK1-ASODN) on murine tumor growth following intratumoral injection, and to explore its potential use in clinical treatment of lung cancer. METHODS: After human lung cancer cells CALU had been inoculated subcutaneously to BALB/c nude mice and grew to tumor nodules, these mice were distributed randomly into three groups: four in the saline group, five in the TANK1-ASODN group, and another five in the sense oligodeoxynucleotides of tankyrase (TANK1-SODN) group. Multiple direct intratumoral injections of TANK1-ASODN, TANK1-SODN or saline were given into the tumor nodules, respectively. The tumor growth and the histopathological characteristics were observed and the expression of ki67 and telomerase hTERT in tumor cells were measured by SABC immunohistrochemical method. RESULTS: After 16 days of continuous injection, the tumor volume of the TANK1-ASODN group was significantly smaller than that of the TANK1-SODN (P < 0.01) and saline-treated groups (P < 0.01); tumor cell degeneration and necrosis were observed in mice treated with TANK1-ASODN. Moreover, a statistically significant decrease in Ki67 labeling index (P < 0.01) and the positive expression ratio of telomerase hTERT (P < 0.01) was observed in the TANK1-ASODN group. CONCLUSIONS: Human lung tumor cell lines express high telomerase activity. TANK1-ASODN can inhibit the activity of telomerase and suppress the proliferation of tumor cells.

Surgical outcomes of gastrointestinal stromal tumors of the stomach: a single unit experience in the era of targeted drug therapy.

The stomach is the most common site of gastrointestinal stromal tumors (GISTs), but the surgical outcomes of gastric GISTs in the era of targeted drug therapy are unclear. This study aimed to assess factors associated with adverse outcomes and to analyze the effects of targeted drug therapy on gastric GISTs. The surgical outcomes and follow-up records of consecutive patients with gastric GISTs treated at Tianjin Medical University Cancer Institute & Hospital between June 2002 and December 2008 were reviewed. Eighty-five patients were included. Surgery was undertaken in all patients with curative intent. Imatinib mesylate was administered preoperatively to 6 (7%) patients (neoadjuvant therapy), and the median durations of therapy were 6 months (range 3-17 months). Imatinib mesylate was administered postoperatively to 18 (21%) patients with high-risk lesions (adjuvant therapy) and 19 (22%) patients with recurrent disease, and the median durations of therapy were 22 months (range 6-24 months) and 25 months (range 1-64 months), respectively. Tumor size greater than 10 cm (P = 0.015), high mitotic index (P = 0.021), and no adjuvant imatinib therapy (P = 0.046) were the only significant factors associated with higher recurrence-free survival in multivariate analysis. Large tumors, high mitotic index, and the absence of imatinib treatment are associated with high recurrence-free survival. Adjuvant imatinib therapy of 2 years appears to decrease the recurrence of gastric GISTs.