Haiquan Chen

Fudan University, Shanghai, Shanghai Shi, China

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Publications (102)527.83 Total impact

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    ABSTRACT: Background Chylothorax is a rare but serious postoperative complication in esophageal cancer patients. The aim of this study was to identify risk factors associated with chylothorax and the indication for surgical intervention.MethodsA consecutive series of 1290 patients who underwent esophagectomy for esophageal cancer was included. Peri-operative data, including postoperative morbidity and mortality, were analyzed.ResultsThirty-four patients (2.6%) developed chylothorax and had significantly higher instances of pneumonia (26.5% vs. 11.1%, P = 0.012) and arrhythmia (17.6% vs. 2.9%, P = 0.001), and a longer hospital stay (22 vs. 18 days, P < 0.001). Reoperation was performed in 11 patients at a rate of 77.8%, 42.9%, 20%, and 0% for chylothorax diagnosed in two, three, four, and >= 5 days, respectively, after esophagectomy (P < 0.001). After three days of conservative therapy, the chest tube output was significantly greater in patients whose medical management had failed than in those successfully treated (P < 0.001). All patients who required reoperation had >= 13.5 ml/kg of drainage (sensitivity 100%); four of 23 patients with successful medical management had a chest tube output >= 13.5 ml/kg (specificity 83%). Logistic regression analysis showed that body mass index (BMI) < 25 was an independent risk factor for chylothorax (hazard ratio = 9.256, P = 0.029).Conclusions Patients with a BMI < 25 are more likely to develop chylothorax after esophagectomy. Operative therapy should be seriously considered in patients who develop chylothorax early postoperatively. In addition, a high daily chylous output of >= 13.5 ml/kg after three days of conservative therapy might be a reliable indicator for reoperation.
    03/2015; DOI:10.1111/1759-7714.12240
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    ABSTRACT: Sweet esophagectomy is performed widely in China, while the Ivor-Lewis procedure, with potential benefit of an extended lymphadenectomy, is limitedly conducted owing to concern for a higher risk for morbidity. Thus, the role of the Ivor-Lewis procedure for thoracic esophageal cancer needs further investigation. To determine whether Ivor-Lewis esophagectomy is associated with increased postoperative complications compared with the Sweet procedure. A randomized clinical trial was conducted from May 2010 to July 2012 at Fudan University Shanghai Cancer Center, Shanghai, China, of 300 patients with resectable squamous cell carcinoma in the middle and lower third of the thoracic esophagus. Intent-to-treat analysis was performed. Patients were randomly assigned to receive either the Ivor-Lewis (n = 150) or Sweet (n = 150) esophagectomy. The primary outcome of this clinical trial was operative morbidity (any surgical or nonsurgical complications). Secondary outcomes included oncologic efficacy (number of lymph nodes resected and positive lymph nodes), postoperative mortality (30-day and in-hospital mortality), and patient discharge. Resection without macroscopical residual (R0/R1) was achieved in 149 of 150 patients in each group. Although there was no significant difference between the 2 groups regarding the incidence of each single complication, a significantly higher morbidity rate was found in the Sweet group (62 of 150 [41.3%]) than in the Ivor-Lewis group (45 of 150 [30%]) (P = .04). More patients in the Sweet group (8 of 150 [5.3%]) received reoperations than in the Ivor-Lewis group (1 of 150 [0.7%]) (P = .04). The median hospital stay was 18 days in the Sweet group vs 16 days in the Ivor-Lewis group (P = .002). Postoperative mortality rates in the Ivor-Lewis (1 of 150) and Sweet (3 of 150) groups were 0.7% and 2.0%, respectively (P = .25). More lymph nodes were removed during Ivor-Lewis esophagectomy than during the Sweet procedure (22 vs 18, P < .001). Early results of this study demonstrate that the Ivor-Lewis procedure can be performed with lower rates of postoperative complications and more lymph node retrieval. Ivor-Lewis and Sweet esophagectomies are both safe procedures with low operative mortalities. clinicaltrials.gov Identifier:NCT01047111.
    02/2015; DOI:10.1001/jamasurg.2014.2877
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    ABSTRACT: Chest computed tomography (CT) scanning has been widely utilized in thymoma identification and staging as well as in follow-up monitoring for recurrence. However, the relationship between some CT imaging features and pathological types, clinical stage, completeness of resection, or prognosis in thymoma has not been well explored. We retrospectively reviewed preoperative CT imaging for 238 thymoma patients, who had undergone thymectomy from October 2007 to December 2011. All CT parameters were assessed in each case based on clinical and pathological data. Survival analysis was performed by using the Kaplan-Meier and log-rank tests. Tumour contours (P = 0.008), homogeneity (P = 0.009), degree of enhancement (P = 0.013), fat plane obliteration with adjacent structures (P < 0.001), the presence of mediastinal lymphadenopathy (P = 0.010), irregular infiltration into the lung (P = 0.012) and tumour shape (P = 0.007) were associated with the World Health Organization (WHO) histological classification. Lobulated or irregular tumour contours (P < 0.001), presence of calcifications (P = 0.002), infiltration of surrounding fat (P < 0.001), irregular infiltration into the lung (P < 0.001), irregular infiltration into vascular (P < 0.001), more abutment of vessels (P < 0.001) and pulmonary changes adjacent to the tumour (P < 0.001) were associated with the more advanced Masaoka-Koga clinical stage. Tumour contours (P < 0.001), infiltration of surrounding fat (P = 0.008), irregular infiltration into the lung (P < 0.001) and degree of abutment of vessel circumference (P = 0.001) were associated with completeness of resection. With multivariate analysis, no CT image features could reliably predict on the overall or disease-free survival rate. CT imaging does have some features, which are significantly correlated with the WHO classification, the Masaoka-Koga clinical staging and the completeness of resection, although it has no definite role to evaluate preoperatively the survival rate of thymoma patients. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 12/2014; DOI:10.1093/ejcts/ezu475 · 2.81 Impact Factor
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    ABSTRACT: There is no consensus about the impact of a high BMI on postoperative morbidity and survival after esophagectomy. The aim of this study was to determine the influence of a high BMI on postoperative complications and survival in a large cohort of esophageal cancer patients. From January 2006 to December 2012, 1,342 consecutive esophageal cancer patients who underwent esophagectomy were included in this study. Patients were divided into three groups: 950 patients were classified as normal BMI (BMI 18.5-24.9 kg/m(2)), 279 were classified as high BMI (BMI ≥ 25 kg/m(2)), and 113 as low BMI (BMI < 18.5 kg/m(2)). Multivariate logistic regression models were used to identify confounding factors associated with postoperative complications. The impact of BMI on overall survival (OS) was estimated by the Kaplan-Meier method and Cox proportional hazard models. The predominance of pathological type was esophageal squamous cell carcinoma (n = 1,280, 95.4 %). Overall morbidity, mortality, and hospital stay did not differ among groups. The incidence of pneumonia was higher in patients with high BMI compared with those with normal BMI (14.7 vs. 9.9 %, P = 0.025). However, chylothorax was less frequent in high-BMI group (0.4 % in high-BMI group, 3.1 % in normal group, and 3.5 % in low group, P = 0.011). Logistic regression analysis revealed high BMI was independently associated with decreased incidence of chylothorax [HR 0.86; 95 % confidence interval 0.76-0.97]. Overweight and obese patients had significantly better overall survival than underweight patients (median OS 55.6 vs. 32.5 months, P = 0.013), while the pathological stage was significantly higher in underweight patients (P = 0.001). In multivariate analysis, T status, N status, differentiation grade, and tumor length were identified as independent prognostic factors. A high BMI is not associated with increased overall morbidity following esophagectomy; moreover, it is associated with decreased incidence of chylothorax. The better overall survival in patients with high BMI compared with those with low BMI might be due to a relatively low pathological stage. A high BMI should therefore not be a relative contraindication for esophagectomy.
    Journal of Cancer Research and Clinical Oncology 11/2014; DOI:10.1007/s00432-014-1878-x · 3.01 Impact Factor
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    ABSTRACT: A total of 1039 stage I-III invasive lung adenocarcinoma including 186 solid subtype patients who have undergone radical resection were assessed for clincopathlogic characteristics, status of common driver mutations, pattern of recurrence, recurrence-free survival (RFS), overall survival (OS), post-recurrence survival (PRS) and predictive value for adjuvant chemotherapy and EGFR tyrosine kinase inhibitors (TKIs). Solid predominant adenocarcinomas were more likely to have initial distant recurrences than non-solid subtype invasive adenocarcinomas (P = 0.018). In univariate analysis, solid predominant adenocarcinoma patients had significantly worse RFS (P < 0.001), OS (P < 0.001) and PRS (P = 0.010). Multivariate analysis adjusting for clinicopathologic variables and mutational status showed that solid subtype was an independent poor prognostic factor (odds ratio = 1.876, 95% confidence interval: 1.291-3.158; P = 0.003) and an independent negative predictor for stage II-III patients undergoing adjuvant chemotherapy (odds ratio = 2.020, 95% confidence interval: 1.291-3.158; P = 0.002). In EGFR-mutated solid predominant lung adenocarcinoma patients who experienced disease recurrence, the response rate to EGFR TKIs was only 37.5%. In radically resected invasive lung adenocarcinoma, solid subtype was an independent poor prognostic factor and negative predictor for adjuvant chemotherapy.
    Scientific Reports 11/2014; 4:7163. DOI:10.1038/srep07163 · 5.08 Impact Factor
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    ABSTRACT: Introduction The recurrent TERT promoter mutations have been recently described in diverse human cancers. We previously showed that over 60% of non-small cell lung cancer from East Asian harbored well-known oncogenic mutations in EGFR and KRAS. Here, we sought to determine the incidence, clinicopathologic characteristics, and association with known oncogenic mutations. Patients and Methods A total of 467 patients treated surgically for primary lung cancer were examined for mutations in TERT promoter using polymerase chain reaction (PCR) followed by Sanger sequencing. Immunohistochemical (IHC) staining was performed to detect the expression of TERT. Clinical characteristics including gender, age, smoking status, tumor size, differentiation, lymph node metastasis, TNM stage, overall survival and relapse-free survival were analyzed. Results Of 467 patients with non-small cell lung cancer, the TERT promoter mutation was detected in 12 patients. Of the 12 patients, 3 with C228 T, 2 with C250 T, 2 with C216 T, 1 with C228A, 1 with C229G, 1 with G267 C, 1 with C295 T and 1 with G233 C. Compared to the TERT mutation negative group, patients with TERT promoter mutation were significantly associated with older age (≥60 years, P = 0.039). No significant difference was found in overall survival (OS) or relapse-free survival (RFS) between TERT with mutation and TERT without mutation. Conclusions TERT promoter mutations are recurrent mutated in 2.57% of NSCLCs and are highly enriched in older patients. It may play an important role in the pathogenesis of NSCLC and may serve as a potential target for therapy.
    Lung Cancer 10/2014; 86(3). DOI:10.1016/j.lungcan.2014.10.009 · 3.74 Impact Factor
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    ABSTRACT: Background Survival difference following lobectomy, segmentectomy, and wedge resection in stage I non-small cell lung cancer (NSCLC) and its subgroups remains undetermined.Methods We systemically searched published articles comparing recurrence-free survival (RFS), overall survival (OS), or cancer-specific survival (CSS) between lobectomy and limited resection or between segmentectomy and wedge resection.ResultsA total of 42 studies published from 1980 to 2014 enrolling 21,926 patients were included in this meta-analysis. Survival results favored lobectomy in stage IA NSCLC ≤2 cm (combined HR: 1.530, 95% CI: 1.402–1.671, P < 0.001) or patient's ≥65 years old (combined HR: 1.227, 95% CI: 1.003–1.502, P = 0.047). Survival outcome of video-assisted thoracoscopic (VATS) sublobectomy was comparable to that of VATS lobectomy (pooled HR: 0.808, 95% CI: 0.556–1.174, P = 0.263). The combined HR of segmentectomy versus lobectomy was 1.231 (95% CI: 1.070–1.417, P = 0.004), while the pooled HR of wedge resection versus segmentectomy was 1.542 (95% CI: 0.856–2.780, P = 0.149).Conclusions This study suggested that tumor size or age alone should not be the criteria to encourage sublobar resection. For stage I NSCLC, survival following segmentectomy was inferior to lobectomy. Patients undergoing intentional sublobectomy achieved comparable survival as those who received lobectomy. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 10/2014; DOI:10.1002/jso.23800 · 2.84 Impact Factor
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    ABSTRACT: The youthful lung cancer may constitute an entity with distinct clinicopathologic characteristics and a controversial prognosis compared with the older counterpart. Whether the youthful lung cancer has the exclusively distinct molecular features has not been well investigated.
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    Xinghua Cheng, Haiquan Chen
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    ABSTRACT: Lung cancer, mostly nonsmall cell lung cancer, continues to be the leading cause of cancer-related death worldwide. With the development of tyrosine kinase inhibitors that selectively target lung cancer-related epidermal growth factor receptor mutations, management of advanced nonsmall cell lung cancer has been greatly transformed. Improvements in progression-free survival and life quality of the patients were observed in numerous clinical studies. However, overall survival is not prolonged because of later-acquired drug resistance. Recent studies reveal a heterogeneous subclonal architecture of lung cancer, so it is speculated that the tumor may rapidly adapt to environmental changes via a Darwinian selection mechanism. In this review, we aim to provide an overview of both spatial and temporal tumor heterogeneity as potential mechanisms underlying epidermal growth factor receptor tyrosine kinase inhibitor resistance in nonsmall cell lung cancer and summarize the possible origins of tumor heterogeneity covering theories of cancer stem cells and clonal evolution, as well as genomic instability and epigenetic aberrations in lung cancer. Moreover, investigational measures that overcome heterogeneity-associated drug resistance and new assays to improve tumor assessment are also discussed.
    OncoTargets and Therapy 09/2014; 7:1689-704. DOI:10.2147/OTT.S66502 · 1.34 Impact Factor
  • Journal of Cancer Research and Clinical Oncology 09/2014; 141(1). DOI:10.1007/s00432-014-1821-1 · 3.01 Impact Factor
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    ABSTRACT: Both micropapillary predominant lung adenocarcinoma according to the IASLC/ATS/ERS classification and lung adenocarcinoma with a micropapillary component have been reported to be associated with poor prognosis. However, whether they have different prognosis remains undetermined.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 09/2014; DOI:10.1097/JTO.0000000000000341 · 5.80 Impact Factor
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    ABSTRACT: Whether the Hippo pathway contributes to cell lineage transition under pathological conditions, especially tumorigenesis, remains largely unknown. Here we show that YAP, the major effector of the Hippo pathway, displays a distinct activation pattern in lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC); YAP is initially activated by LKB1 loss in lung ADC, which upregulates ZEB2 expression and represses DNp63 transcription in a default manner. During transdifferentiation, YAP is inactivated, which in turn relieves ZEB2-mediated default repression of DNp63 and triggers squamous differentiation reprogramming. Disruption of the YAP barrier for phenotypic transition significantly accelerates squamous transdifferentiation, whereas constitutive YAP activation conversely inhibits this transition. More importantly, ectopic DNp63 expression rescues the inhibitory effect of YAP on squamous transdifferentiation. These findings have established YAP as an essential barrier for lung cancer cell fate conversion and provided a mechanism for regulating cancer plasticity, which might hold important implication for YAP-targeted therapies.
    Nature Communications 08/2014; 5:4629. DOI:10.1038/ncomms5629 · 10.74 Impact Factor
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    ABSTRACT: Current criteria for identification of synchronous non-small cell lung cancers (NSCLCs) may be confusing in patients with lymphatic metastases. This study was aimed at investigating the strategy using both the new histologic classification and driver-mutational testing to define multiple primary lung cancers. Prospectively collected data of surgical patients with synchronous NSCLCs were retrospectively analyzed. Cases were defined using the Martini-Melamed criteria, and validated by histologic subtyping based on the new classification and driver mutation of selected genes. Survival was estimated between patients with multiple primary and metastatic disease controlling by nodal (N) stage. Factors associated with prolonged survival were evaluated using the Cox proportional hazards mode. A total of 131 patients followed for at least 12 months were included in this study. Controlling by N0 stage, patients who were diagnosed with multiple primary NSCLCs showed better relapse-free survival (RFS) than those with intrapulmonary metastases categorized either by the Martini-Melamed criteria or by histologic-mutational methods (both p < 0.0001). However, at N+ stage, patients stratified by Martini-Melamed criteria showed no difference in survival (p = 0.517), while those defined by histologic-mutational methods maintained superior survival compared with the control group (p = 0.042). On multivariate analysis, only N0 and diagnosis of independent lung lesions by histologic-mutational methods were significant predictors of better RFS (p = 0.031 and 0.001, respectively) The histologic-mutational strategy may be an option for identification of synchronous NSCLC when traditional criteria were not applicable, especially in cases with positive lymphatics. N0 stage and the diagnosis of independent pulmonary tumors were associated with better RFS.
    Annals of Surgical Oncology 08/2014; 21(13). DOI:10.1245/s10434-014-3840-1 · 3.94 Impact Factor
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    ABSTRACT: Background To have a comprehensive investigation of the clinicopathologic, histologic and cytologic features of fusion-positive lung adenocarcinomas. Methods Quantitative real-time reverse transcriptase PCR (qRT-PCR) and reverse transcriptase PCR (RT-PCR) were simultaneously performed to screen ALK, ROS1 and RET fusions in resected tumor samples from 1139 Chinese lung adenocarcinoma patients, with validation of positive results using fluorescent in situ hybridization. Clinicopathologic characteristics, predominant histologic subtype and cytomorphology were assessed in fusion-positive lung adenocarcinomas and compared to those harboring EGFR, KRAS, HER2 or BRAF mutations. Results There were 58 (5.1%) ALK fusions, 11 (1.0%) ROS1 fusions and 15 (1.3%) RET fusions. Tumors with ROS1 fusions had significantly larger diameter than ROS1 fusion-negative tumors (P = 0.007), whereas all the 15 tumors harboring RET fusions were ≤ 3 cm in diameter (P = 0.001). The three fusion genes were all more prevalent in solid-predominant adenocarcinoma. Compared to fusion-negative lung adenocarcinomas, tumors harboring a fusion gene had significantly higher prevalence of extracellular mucin (P < 0.001), cribriform pattern (P < 0.001), signet ring cells (P < 0.001) and hepatoid cytology (P < 0.001). No significant difference in relapse-free survival (P = 0.147) and overall survival (P = 0.444) was observed between fusion-positive and fusion-negative patients. Conclusions This study showed fusion-positive lung adenocarcinomas had identifiable common and fusion-pattern specific clinicopathologic, histologic and cytologic features, offering implications for fusion genes screening.
    Lung cancer (Amsterdam, Netherlands) 06/2014; DOI:10.1016/j.lungcan.2014.02.007 · 3.74 Impact Factor
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    ABSTRACT: Purpose-The FGFR3 fusion genes have been recently demonstrated in a subset of non-small cell lung cancer. To aid in identification and treatment of these patients, we examined the frequency, clinicopathologic characteristics and treatment outcomes of patients who had non-small cell lung cancer (NSCLC) with or without FGFR fusions. Experimental Design-Fourteen known FGFR fusion variants, including FGFR1, FGFR2 and FGFR3, were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and verified by direct sequencing in 1328 patients with NSCLC. All patients were also analyzed for mutations in EGFR, KRAS, HER2, BRAF, ALK, RET and ROS1. Clinical characteristics including age, sex, smoking status, stage, subtypes of lung adenocarcinoma, relapse-free survival (RFS) and overall survival (OS) were collected. Results-Of 1328 tumors screened, 2 (0.2%) were BAG4-FGFR1 fusion and 15 (1.1%) were FGFR3-TACC3 fusion. Six of 1016 patients with lung adenocarcinoma were FGFR3-TACC3 fusions and 11 of 312 lung squamous cell carcinoma harbored BAG4-FGFR1 or FGFR3-TACC3 fusions. Compared to the FGFR fusion negative group, patients with FGFR fusions were more likely to be smokers (94.1%, 16 of 17 patients, p<0.001), significantly associated with larger tumor (>3cm) (88.2%, 15 of 17 patients, p<0.001) and with a tendency to be more poorly differentiation (53.9%, 9 of 17 patients, p=0.095). Conclusions-FGFR fusions define a molecular subset of NSCLC with distinct clinical characteristics. FGFR is a druggable target and patients with FGFR fusions may benefit from FGFR targeted therapy which needs further clinical investigation.
    Clinical Cancer Research 05/2014; 20(15). DOI:10.1158/1078-0432.CCR-14-0284 · 8.19 Impact Factor
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    ABSTRACT: Metastasis is the major cause for high mortality of lung cancer with the underlying mechanisms poorly understood. The scaffolding protein NEDD9 has been identified as a pro-metastasis gene in several types of cancers including melanoma and breast cancer. However, the exact role and related mechanism of NEDD9 in regulating lung cancer metastasis still remain largely unknown. Here we demonstrate that NEDD9 knockdown significantly inhibits migration, invasion and metastasis of lung cancer cells in vitro and in vivo. The pro-metastasis role of Nedd9 in lung cancer is further supported by studies in mice models of spontaneous cancer metastasis. Moreover, we find that NEDD9 promotes lung cancer cell migration and invasion through the induction of Epithelial-Mesenchymal Transition (EMT) potentially via FAK activation. More importantly, NEDD9 expression inversely correlates with E-cadherin expression in human lung cancer specimens, consistent with the findings from in vitro studies. Taken together, this study highlights that NEDD9 is an important mediator promotes lung cancer metastasis via EMT. © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 05/2014; 134(10). DOI:10.1002/ijc.28568 · 5.01 Impact Factor
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    ABSTRACT: Controversy persists regarding the adequate extent of lymph node (LN) dissection in thoracic esophageal cancer (EC) surgery. Oncologic efficacy should be balanced with the increased risk of postoperative complications after aggressive radical LN dissection. Here, we evaluate the effectiveness of common hepatic artery LN dissection in surgery for thoracic esophageal squamous cell carcinoma.
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    ABSTRACT: The number of negative lymph nodes (NLNs) can be used for predicting clinical outcomes for patients with esophageal carcinoma as it is believed to reflect the extent of lymphadenectomy. However, when patients are treated with the same surgical procedure, its prognostic value is not clear. We reviewed the records of 332 patients with thoracic esophageal squamous cell carcinoma (ESCC) who underwent three-field lymphadenectomy (3FLND) and had at least 15 lymph nodes removed. We used Kaplan-Meier estimates to compute overall survival (OS), the log-rank tests to assess the equality of survival rates, and Cox regression analyses to evaluate the association between survival and NLN count after adjusting for potential confounders. At a median follow-up interval of 36 months, the median OS was 47 months and the 5-year survival rate was 47.0 %. NLN count was independently associated with OS, and higher numbers of NLNs were linked to better OS (hazard ratio [HR] 0.970; 95 % confidence interval [CI] 0.955-0.986); the effect did not change after we stratified patients into node-negative (HR 0.966; 95 % CI 0.933-1.000) and node-positive (HR 0.973; 95 % CI 0.955-0.991) groups. The NLN count is an important independent prognostic factor for patients with thoracic ESCC treated with 3FLND.
    Annals of Surgical Oncology 04/2014; 21(9). DOI:10.1245/s10434-014-3665-y · 3.94 Impact Factor
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    ABSTRACT: The clinicopathologic characteristics of tumors expressing programmed death (PD-1) ligands (PD-Ls) PD-L1 or PD-L2 and their associations with common driver mutations in lung adenocarcinoma are not clearly defined, despite the progression of anti-PD-1/PD-L1 immunotherapy. PD-L1 and PD-L2 expression was measured by immunohistochemistry in 143 surgically resected lung adenocarcinomas and was correlated with clinical variables, histologic subtypes, and the mutational status of EGFR, KRAS, HER2, and ALK. Positive PD-L1 expression was significantly associated with more advanced T status, N status, and pathologic stage. Histologically, lung adenocarcinomas with positive PD-L1 staining were less likely to be adenocarcinoma in situ or minimally invasive adenocarcinoma and more likely to have solid predominant subtype. Both PD-L1 expression (odds ratio =1.984, 95% confidence interval =1.010-3.894; P=0.047) and PD-L2 expression (odds ratio =2.328, 95% confidence interval =1.201-4.512; P=0.012) were independent predictors of poor overall survival. When the combined PD-L expression and pathologic stage were used together to predict overall survival, the concordance index increased to 0.763, and the Akaike information criteria value decreased to 356.08. We defined the clinicopathologic features of lung adenocarcinomas with high expression of PD-L1 and PD-L2. We further demonstrated the role of PD-L expression as a useful prognostic marker for lung adenocarcinoma.
    OncoTargets and Therapy 04/2014; 7:567-73. DOI:10.2147/OTT.S59959 · 1.34 Impact Factor
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    ABSTRACT: We performed this analysis to improve the understanding of the clinicopathological characteristics and clinical outcome of non-small cell lung cancer (NSCLC) patients harboring the primary epidermal growth factor receptor (EGFR) T790M mutation along with activating EGFR mutation. Resected tumors from 1903 NSCLC patients were analyzed for mutation in EGFR, as well as KRAS (Kirsten rat sarcoma viral oncogene homolog), BRAF (v-raf murine sarcoma viral oncogene homolog B), HER2 (human epidermal growth factor 2), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha), and EML4 (echinoderm microtubule associated protein like 4)-ALK (anaplastic lymphoma receptor tyrosine kinase) fusion. Fluorescence in situ hybridization was performed to define EGFR and c-MET (met proto-oncogene gene amplification. Expression of PIK3CA and p-Akt (phosphorylated protein kinase B) were tested using immunohistochemistry. Clinical and pathological data, including sex, age at diagnosis, stage, tumor differentiation, smoking history, histological subtype, relapse-free and overall survival, were further analyzed. In all, 16 NSCLC patients were found to harbor primary EGFR T790M mutation, including 14 adenocarcinomas and two adenosquamous carcinomas, accounting for 2.04% of all the EGFR mutant cases and 0.84% of the total. No c-MET amplification was found to coexist with primary EGFR T790M. Fewer EGFR copy-number variations were found in samples harboring EGFR T790M mutations compared with those in patients with exon 19 deletions and L858R. Overall survival was significantly shorter for patients harboring EGFR T790M mutation than it was for patients with exon 19 deletions (logrank P=0.008). When taking patients harboring EGFR L858R or exon 19 deletions as one group, the overall survival was also significantly longer than that in patients with T790M mutation (logrank P=0.012). There was no significant difference in relapse-free survival among three subgroups of patients. Our study described the clinicopathological and molecular characteristics of NSCLC patients harboring primary EGFR T790M mutations. Its value of being a predictor for worse prognosis was established. Primary EGFR T790M mutation is a rare event in NSCLC cases, but the therapeutic strategies for this subtype of patients should be precisely considered.
    OncoTargets and Therapy 04/2014; 7:513-24. DOI:10.2147/OTT.S60122 · 1.34 Impact Factor

Publication Stats

1k Citations
527.83 Total Impact Points

Institutions

  • 2009–2015
    • Fudan University
      • Department of Oncology
      Shanghai, Shanghai Shi, China
  • 2013
    • Vanderbilt University
      • Department of Biomedical Informatics
      Нашвилл, Michigan, United States
  • 2012
    • Shanghai Institutes for Biological Sciences
      Shanghai, Shanghai Shi, China
    • Massachusetts General Hospital
      • Department of Pathology
      Boston, Massachusetts, United States
  • 2010
    • Shanghai Jiao Tong University
      Shanghai, Shanghai Shi, China