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Purpose The aim of this study was to evaluate the predictive and prognostic value of peripheral blood survivin and VEGF mRNA expression levels in non-small cell lung cancer (NSCLC) patients. Patients and methods Fifty-eight patients with stage I-IIIA NSCLC who underwent surgical resection were enrolled in this study. Thirty-six patients with benign lung disease (BLD) entered this study as control group. Quantitative real-time PCR was used to detect survivin and VEGF mRNA levels in the cell fraction of peripheral blood in NSCLC patients before and after surgery and BLD patients. The relationship between blood survivin and VEGF mRNA levels and patients clinicopathologic parameters and prognostic factors were investigated. Results The levels of survivin and VEGF mRNA were decreased significantly after surgery in NSCLC patients ( P =0.024 and P =0.012 respectively). Tumor recurrence was significantly more frequent in NSCLC patients with survivin and VEGF mRNA positivity postoperation than in patients without ( P =0.003 and P =0.006, respectively). Patients with survivin or VEGF mRNA positivity postoperation had markedly shorter disease-free survival (DFS) and overall survival (OS) than patients without ( P =0.023 and P =0.016 for survivin; P =0.031 and P =0.025 for VEGF, respectively). Multivariate analysis showed that survivin positivity preoperation ( P =0.026, P =0.041, respectively) and postoperation ( P =0.003, P =0.005, respectively) and VEGF mRNA positivity postoperation ( P =0.007, P =0.009, respectively) were independently associated with DFS and OS. Conclusion Although the levels of surviving and VEGF mRNA were decreased significantly after surgery, postoperative detections of survivin and VEGF mRNA by quantitative real-time PCR could be used as tools to monitor tumor recurrence and predict prognosis.

Lymph node metastasis is a major prognostic factor in resected non-small cell lung cancer (NSCLC). However, 30-40 % rate of recurrence after performing complete resection in node-negative patients suggests that their nodal staging is suboptimal. We aimed to evaluate the molecular diagnosis and prognostic significance of lymph node micrometastasis in patients with node-negative NSCLC. Primary tumor samples from 62 patients with resected stage I-IIB NSCLC were screened for fragile histidine triad (FHIT) and CDKN2A mRNA deletion using reverse transcriptase polymerase chain reaction (RT-PCR). The molecular alternations were found in tumors of 49 patients. A total of 269 lymph nodes from these 49 NSCLC patients with FHIT or/and CDKN2A deletion tumors were examined. Fifteen positive-control nodes and ten negative-control nodes were also analyzed for FHIT and CDKN2A mRNA deletion. Thirty-nine (22 %) and 22 (18 %) lymph nodes from the 49 patients with FHIT and CDKN2A mRNA deletion in primary tumor had FHIT and CDKN2A mRNA deletion, respectively. The types of FHIT and CDKN2A mRNA deletion in lymph nodes were identical with those in their primary tumors. By combination of two markers, 16 patients (32.7 %) were found to have nodal micrometastasis. Survival analysis showed that patients with nodal micrometastasis had reduced disease-free survival (P = 0.001) and overall survival (P = 0.002) rates. Multivariate analysis demonstrated that nodal micrometastasis was an independent predictor for worse prognosis. Thus, the detection of lymph node micrometastasis by FHIT and CDKN2A mRNA deletion RT-PCR will be helpful to predict the recurrence and prognosis of patients with completely resected stage I-IIB NSCLC.

Aim: To evaluate the efficacy of current chemoradiotherapy on improvement of survival in patients with superior sulcus non-small cell lung cancer (NSCLC). Methods: We retrospectively reviewed the data of 39 patients with superior sulcus NSCLC treated with induction therapy followed surgery. The patients were divided into two groups according to the induction approach: the induction radiotherapy (RT) group (1993–1999), and the induction chemoradiotherapy (CT/RT) group (since 1999). Results: The rate of complete resection was 65 percent in the RT group (n = 17) compared with 91 percent in the CT/RT group (n = 22, P = 0.024). Complete pathological responses from induction therapy were 12 percent in the RT group and 45 percent in the CT/RT group (P = 0.032). Overall survival (OS) was significantly longer in patients who received CT/RT than that in those who received RT, with 2- and 5-year survival rates of 77.3 percent and 36.4 percent versus 41.2 percent and 11.8 percent, respectively (P = 0.007). CT/RT also associated with a markedly longer tumor-free survival (TFS), with a median TFS of 40 and 17 months, respectively (P = 0.007). Patients achieved complete resection or complete pathological response had a significantly better survival than those with incomplete resection or pathological partial responses and no change (P

The development of resistance to chemotherapy is one of the major obstacles in the treatment of non-small cell lung cancer (NSCLC). The purpose of this study was to investigate the prognostic value of multidrug resistance protein 1 (MRP1), breast cancer resistance protein (BCRP), lung resistance-related protein (LRP), and excision repair cross-complementing 1 (ERCC1) in NSCLC patients receiving cisplatin-based adjuvant chemotherapy (cisplatin plus vinorelbine or gemcitabine) after tumor resection. We used semiquantitative reverse-transcription polymerase chain reaction to detect the expression of MRP1, BCRP, LRP and ERCC1 mRNA in surgical resection specimens of 60 patients with stage IB through IIIA NSCLC. The expression level of each gene was analyzed in relation to clinicopathological factors, tumor-free survival (TFS), and overall survival. The results showed that stage IIIA (p=0.011), N1 and N2 status (p=0.008), high expression of MRP1 (p=0.034) and LRP (p=0.018) were associated with shorter TFS. Stage IIIA (p=0.0105), N1 and N2 status (p=0.009), high expression of MRP1 (p=0.021) and ERCC1 (p=0.012) were related to a shorter overall survival. Cox multivariate analyses revealed that early stage (p=0.013 and p=0.024), negative lymph node status (p=0.006 and p=0.011), and low MRP1 expression (p=0.022 and p=0.035) were independent predictors of favorable TFS and overall survival, respectively. Additionally, ERCC1 (p=0.019) was an independent predictor of favorable overall survival.

Background The survival rates for stage IIIA and stage IIIB Non–Small-cell lung cancer (NSCLC) are extremely poor with single-treatment modalities such as radiation therapy or surgery. The purpose of this study is to assess tolerability, response, surgical resectability, and survival of chemotherapy followed by chemoradiation therapy, and then followed by surgery in patients with stage IIIA (N2-bulky) or stage IIIB NSCLC. Patients and Methods Forty-eight patients with stage IIIA (N2-bulky) or stage IIIB (T4 N1-2 M0) NSCLC received 2 cycles of chemotherapy with cisplatin, mitomycin, and vindesine, subsequent radiation therapy (45 Gy, twice-daily 1.5 Gy) with simultaneous low-dose cisplatin and vindesine, followed by surgery. Results Forty-five patients completed induction chemoradiation therapy. Thirty-three patients (68.8%) had clinical response to induction treatment. Thirty-nine patients underwent a thoracotomy, with a complete resection rate of 62.5% (30/48). The pathologic response rate was 60% (27/45), with complete pathologic response of 8 patients. The median survival time for the total group of 48 patients was 23 months, with 3- and 5-year survival rates of 41.7% and 31.8%, respectively. Multivariate analysis showed that complete resection and pathologic response in surgical specimens were independent predictors of survival ( P = .048 and P = .022). Conclusion Preoperative sequence of chemotherapy followed by concurrent chemoradiation therapy is an effective approach in patients with stage IIIA (N2-bulky) and IIIB (T4 N1-2 M0) NSCLC. The operation after induction chemoradiation therapy should be performed in carefully selected patients with surgically resectable diseases. The patients who achieved complete resection and with pathologic response of tumor can benefit from surgery following induction chemoradiation therapy.

Aim: The aim of this study was to evaluate the efficacy of cisplatin plus vinorelbine as a regimen of neoadjuvant chemotherapy on the improvement of surgical resectability and survival in Chinese patients with stage IIIA non-small cell lung cancer (NSCLC). Methods: Fifty-six patients with stage IIIA NSCLC were randomly assigned to undergo either surgery preceded by two cycles of chemotherapy with cisplatin plus vinorelbine (the neoadjuvant chemotherapy arm) or immediate surgery (the primary surgery arm). The patients who had a complete resection received two to four cycles of chemotherapy, and those with incomplete resection received radiotherapy followed by two cycles of chemotherapy after surgery. Results: The overall response rate to neoadjuvant chemotherapy was 53.6%, with a complete response of 7.1%. A pathological complete response was seen in two patients (8%). The complete resection rates were 78.6% in the neoadjuvant chemotherapy arm and 60.7% in the primary surgery arm. The median overall survival and median disease-free survival was 30 months and 24 months, respectively, in the neoadjuvant chemotherapy arm as compared to 16 months and 11 months in the primary surgery arm (P = 0.04 and P = 0.048). The 3-year and 5-year survival rate was 49.7% and 31.9%, respectively, for the neoadjuvant chemotherapy arm and 29.2% and 3.6% for the primary surgery arm. Conclusion: Neoadjuvant chemotherapy with cisplatin plus vinorelbine regimen is effective and tolerable and can improve the overall survival and disease-free survival time in Chinese patients with stage IIIA NSCLC.

In a previous study, survivin mRNA expression in non-small cell lung cancer (NSCLC) tissue had been demonstrated to be associated with unfavorable prognosis of patients treated with chemotherapy. In this study, we investigated the survivin mRNA levels in blood of patients with stage IIIA-N2 NSCLC and their association with the efficacy of neoadjuvant chemotherapy (NCT) and disease-free survival (DFS) and overall survival (OS). Blood specimens were collected from 56 patients with stage IIIA-N2 NSCLC before (N0) and after the complete of NCT (N1). Survivin mRNA was measured by real-time quantitative-PCR assay. Receiver operating characteristics curve analysis was undertaken to determine the best cutoff value for survivin mRNA. Results showed that high blood survivin mRNA levels at N0 and N1 were significantly associated with clinical (P = 0.01 and P = 0.008, respectively) and pathologic response (both P = 0.004, respectively). Moreover, the change of blood survivin mRNA levels in these NSCLC patients is associated with the clinical and pathologic response to NCT. Patients with high survivin mRNA levels at N0 and N1 had significantly shorter DFS and OS than those with low survivin mRNA levels (P = 0.021 and P = 0.014, respectively for DFS; P = 0.009 and P = 0.005, respectively for OS). Multivariate analysis demonstrated that high blood survivin mRNA level was an independent predictor for worse DFS and OS in the NSCLC patients receiving NCT. In conclusion, survivin mRNA level in blood from stage IIIA-N2 NSCLC patients receiving NCT is predictive of cancer outcome.

LUNX is a lung-specific gene whose messenger ribonucleic acid (mRNA) expression is strictly limited to normal lung tissue and nonsmall cell lung cancer (NSCLC) tissue. The aim of this study was to investigate whether the detection of LUNX mRNA-positive circulating tumor cells (CTC)s in peripheral blood at different time points is useful for predicting disease recurrence, disease-free survival (DFS), and overall survival (OS) in NSCLC patients undergoing surgery. Serial blood samples from 68 patients with stage I-IIIA NSCLC were examined by real-time quantitative polymerase chain reaction assay targeting LUNX mRNA before (T0) and after surgery (T1) and after the completion of adjuvant chemotherapy (T2). Results showed that LUNX mRNA-positive CTCs were detected in 40 of 68 NSCLC patients (58.8%) before surgery; the detection rates of LUNX mRNA-positive CTCs at T1 and T2 time points were 32.4% (22/68) and 33.3% (20/60), respectively. The detection of LUNX mRNA-positive CTC at 3 time points was associated with lymph node status and pathologic stage. During the follow-up period, patients with LUXN mRNA-positive CTC at 3 time points had a higher relapse rate and a shorter DFS and OS than those without. Multivariate analysis revealed that presence of LUNX mRNA-positive CTC at T1 and T2 time points was an independent unfavorable factor for DFS and OS. In conclusion, detection of LUNX mRNA-positive CTC after surgery and the completion of adjuvant chemotherapy in patients with stage I-IIIA NSCLC are highly predictive for DFS and OS. This technique could aid in the prediction of prognosis and design of tailored treatment.

The long-term survival of patients with completely resected stage I non-small cell lung cancer (NSCLC) is not optimal because of undetected lymph node micrometastasis at the time of surgery. The aim of this study is to evaluate the role of survivin and livin mRNA expression in histopathologically negative lymph nodes of stage I NSCLC patients as markers of micrometastasis. Clinical data and tissue samples of primary tumor and lymph nodes were collected from 44 patients with stage I NSCLC. Reverse-transcriptase-PCR (RT-PCR) was used to detect survivin and livin mRNA expression in these tumor and lymph node samples. Survivin mRNA was detected in all tumors, and livin mRNA was detectable in 39 of the 44 primary tumors. The cut-off values of survivin and livin mRNA levels for diagnosing micrometastasis in lymph nodes were set up according to the expression of survivin and livin mRNA in control lymph nodes. Fifteen (34.1 %) of 44 stage I NSCCL patients had micrometastasis in lymph nodes by survivin and/or livin mRNA positive expression. Survival analysis showed higher rate of cancer recurrences and tumor-related death in patients with lymph node micrometastasis (P

Purpose The aim of this study was to investigate prognostic value of multidrug resistance protein 1 (MRP1), breast cancer resistance protein (BCRP), lung resistance-related protein (LRP) and excision repair cross-complementing 1 (ERCC1) in patients with locally advanced non-small cell lung cancer (NSCLC) who received neoadjuvant cisplatin-based chemotherapy. Methods Transbronchial biopsy (TBB) specimens from 46 patients with stage IIIA (N 2 ) NSCLC were collected to determine the expression level of MRP1, BCRP, LRP and ERCC1 mRNA by semiquantitative RT-PCR. The expression level of each gene was analyzed in relation to histopathologic response to chemotherapy, and tumor-free survival (TFS) and overall survival. Results Patients with MRP1 or LRP low expression had a significantly better histopathologic response ( P =0.032 and 0.006), and a significantly longer TFS ( P =0.043 and 0.025) and overall survival ( P =0.019 and 0.013) than those with MRP1 or LRP high expression. Patients with ERCC1 low expression had a significantly longer overall survival ( P =0.007), but not TFS ( P =0.094) than those with ERCC1 high expression. In multivariate analysis, LRP low expression was a significantly favorable factor for TFS ( P =0.027), and LRP and ERCC1 were significantly favorable factors for overall survival ( P =0.012 and 0.032). Conclusion Assessment of MRP1 and LRP mRNA expression in TBB specimens may predict histopathologic response and survival in locally advanced NSCLC patients who received neoadjuvant cisplatin-based chemotherapy. ERCC1 expression was predictive for overall survival.

Background: Prognosis of stage IIIA N2 non-small cell lung cancer (NSCLC) remains poor despite the changes in therapeutic strategies. Objectives: To assess long term results of neo adjuvant therapy followed by surgery for patients with stage IIIA N2 NSCLC and to analyze factors influencing survival. Materials and Methods: The methods adopted include: Retrospective review of medical records of 91 patients with stage IIIA N2 NSCLC, who received neo adjuvant therapy followed by surgery; collection of information on demographic information, staging procedure, preoperative therapy, clinical response, type of resection, pathologic response of tumor, status of lymph nodes and adjuvant chemotherapy; survival analysis by Kaplan-Meier and calculation of prognostic factors using log-rank and Cox regression model. Results: All patients received a platinum-based chemotherapy and 23 (29.1%) had an associated radiotherapy. Eighty four patients underwent thoracotomy. Median survival was 26 months (95%CI, 22.6-30.8 months) with three and five year survival rates of 31.6 and 20.9%, respectively. Prognostic factors for survival on univariate analysis was clinical response (P = 0.032), complete resection (P = 0.002), pathologic tumor response ( P < 0.001), and lymph nodal down staging (P = 0.001). Multivariate analyses identified complete resection, pathologic tumor response and lymph nodal down staging as independent prognostic factors. Conclusion: Survival of patients with stage IIIA N2 NSCLC who received neo adjuvant therapy is significantly influenced by clinical response, complete resection, pathologic tumor response, and lymph nodal down staging. These results can be helpful in guiding standard clinical practice and evaluating the outcome of neo adjuvant therapy followed by surgery in patients with stage IIIA N2 NSCLC.