[Show abstract][Hide abstract] ABSTRACT: Objectives:
SOX2 is a gene that encodes for a transcription factor, which functions as an activator or suppressor of gene transcription. SOX2 amplification and overexpression have been found in various types of tumors and play important roles in cancer cells. The aim of the study was to evaluate SOX2 expression and amplification in lung squamous cell carcinomas (SCCs) and to determine the relationship with main clinicopathologic features, patient prognosis, and common driver mutations.
Materials and methods:
SOX2 protein levels were measured by immunohistochemistry, while SOX2 copy numbers were measured by fluorescence in situ hybridization in resected samples from 162 Chinese lung SCC patients. All patients were also analyzed for mutations in EGFR, HER2, BRAF, PIK3CA, NFE2L2, and FGFR fusion genes. Clinical characteristics, including age, sex, smoking status, stage, relapse-free survival (RFS), and overall survival (OS), were collected.
SOX2 overexpression and amplification were observed in 58.6% and 45.9% of lung SCCs. Lung SCC patients with SOX2 overexpression were significantly associated with absence of malignant tumor family history (P=0.021), FGFR fusion gene (P=0.046), longer RFS (P=0.041), and OS (P=0.025). No correlation was found between SOX2 gene amplification and main clinicopathologic features, patient prognosis, or common driver mutations.
SOX2 overexpression and amplification are common in lung SCCs. SOX2 over-expression was associated with FGFR fusion genes and predicted favorable outcome in lung SCCs. The underlying relationship of SOX2 and FGFR still needs further investigation.
OncoTargets and Therapy 11/2015; 8:3009-16. DOI:10.2147/OTT.S91293 · 2.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
B-cell-lymphoma-2 (Bcl-2) is a proto-oncogene that plays an important role in the regulation of apoptosis and cell survival. However, there are much conflicting data in the literature concerning the association between Bcl-2 and prognosis in non-small-cell lung cancer (NSCLC). There is little in the way of meta-analysis focused on Bcl-2 and its effect on NSCLC prognosis. This study was performed to provide an assessment of whether expression levels of Bcl-2 are associated with prognosis in patients with NSCLC.
Materials and methods:
We searched PubMed, the Cochrane Library, and China National Knowledge Infrastructure for all eligible studies. The combined hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) in terms of overall survival were evaluated.
Fifty published studies including 6,863 patients with lung cancer were included in this meta-analysis. Overall, Bcl-2 was expressed in 33% of the NSCLC tumors studied. Our analysis indicates that NSCLC patients with Bcl-2-positive expression have a better prognosis than those with Bcl-2-negative expression in both Asian and non-Asian study populations (HR 0.79, 95% CI 0.72-0.87, P<0.00001). However, Bcl-2-positive expression seems to have no significant impact on survival of stage I NSCLC patients.
Our results indicated that Bcl-2 might be a useful prognostic marker for NSCLC generally. Larger clinical trials are needed to confirm the prognostic value of Bcl-2 in stage I NSCLC.
OncoTargets and Therapy 11/2015; 8:3361. DOI:10.2147/OTT.S89275 · 2.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
The aim of this study was to evaluate the clinical features of T1aN2M0 stage non-small cell lung cancer (NSCLC).Method
From November 2008 to May 2013, 498 patients with T1a-stage NSCLC who visited the Shanghai Cancer Center were included in the study. All patients underwent a lobectomy or segmentectomy with systematic nodal resection for primary lung cancer. Analyses of gender, smoking history, primary tumor site, tumor location, tumor size, pathological classification, cancer gene, pleural invasion, number of positive lymph nodes, skip N2, single or multiple station N2, progression-free survival (PFS), and overall survival (OS) were performed.ResultThere were significant differences in tumor size, tumor size distribution, adenocarcinoma subgroup, and number of positive lymph nodes between patients at T1aN2M0 and T1aN0M0 stages. The most common histology of the T1aN2M0 subgroup was adenocarcinoma. Epidermal growth factor receptor mutations were the most common gene mutation in T1aN2M0 stage NSCLC. There were significant differences in five-year OS and PFS rates between patients with T1aN2M0, T1aN0M0, and T1aN1M0 stages. Multivariate analyses of mediastinal lymph node metastasis showed that gender, tumor size distribution, and histology type were significant predictive factors. Multivariate analyses of OS and PFS rates in the T1aN2M0 subgroup showed that the number of positive lymph nodes was a significant predictive factor.Conclusion
Gender, tumor size distribution, and histology type were independent predictors of mediastinal lymph node metastasis in patients with T1a stage. The number of positive lymph nodes was significantly associated with OS and PFS rates in patients with T1aN2M0 stage NSCLC.
Thoracic Cancer 11/2015; DOI:10.1111/1759-7714.12314 · 0.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To determine the frequency of driver mutations in Chinese non-small cell lung cancer (NSCLC) patients.
Comprehensive mutational analysis was performed in 1356 lung adenocarcinoma, 503 squamous cell carcinoma, 57 adenosquamous lung carcinoma, 19 large cell carcinoma and 8 sarcomatoid carcinoma. The effect of EGFR tyrosine kinase inhibitors (TKIs) on EGFR-mutated lung adenocarcinoma patients after disease recurrence was investigated.
Mutations in EGFR kinase domain, HER2 kinase domain, KRAS, BRAF, ALK, ROS1 and RET were mutually exclusive. In lung adenocarcinoma cases "pan-negative" for the seven above-mentioned driver mutations, we also detected two oncogenic EGFR extracellular domain mutations (A289D and R324L), two HER2 extracellular and transmembrane domain mutations (S310Y and V659E), one ARAF S214C mutation and two CD74-NRG1 fusions. Six (1.2%) FGFR3 activating mutations were identified in lung squamous cell carcinoma (five S249C and one R248C). There were three (15.8%) EGFR mutations and four (21.1%) KRAS mutations in large cell carcinoma. Three (37.5%) KRAS mutations were detected in sarcomatoid carcinoma. In EGFR-mutated lung adenocarcinoma patients who experienced disease recurrence, treatment with EGFR TKIs was an independent predictor of better overall survival (HR = 0.299, 95% CI: 0.172-0.519, P < 0.001).
We determined the frequency of driver mutations in a large series of Chinese NSCLC patients. EGFR TKIs might improve the survival outcomes of EGFR-mutated lung adenocarcinoma patients who experienced disease recurrence.
[Show abstract][Hide abstract] ABSTRACT: Our aim was to investigate the clinical and pathologic characteristics of the epidermal growth factor receptor (EGFR) exon 18 mutations in East Asian lung adenocarcinomas patients. A total of 1,201 lung adenocarcinomas were analyzed for mutation in EGFR. Clinical and pathologic characteristics of patients with EGFR exon 18 mutations were compared with those who harbored classic activating mutations (exon 19 deletions and the L858R point mutation). The mutations in EGFR exon 18 were observed in 2.8% of 1,201 lung adenocarcinomas and 4.6% of patients with EGFR mutations. Patients with a single EGFR exon of 18 mutations had a worse overall survival than those harboring the complex EGFR exon of 18 mutations (p = 0.002) or those with classic activating mutations (p = 0.014). Four of five patients with EGFR exon 18 mutations showed objective response to the EGFR-TKI therapies after disease recurrence. Our results demonstrated that single EGFR exon 18 mutations may be an indicator of poor prognosis compared with complex EGFR exon 18 mutations or classic mutations. Furthermore, the results of the current study will be helpful for decision-making in the treatment of patients with EGFR exon 18 mutations.
[Show abstract][Hide abstract] ABSTRACT: The epidermal growth factor receptor (EGFR) signaling pathway is important in regulating biological behaviors in many malignancies. We explored whether expression and activation of EGFR and several components on its downstream pathways have prognostic significance in patients with esophageal squamous cell carcinoma (ESCC).
Expression of EGFR, phosphorylated (p)-EGFR, AKT1, p-AKT1, AKT2, p-AKT2, ERK1, ERK2, p-ERK1/2, STAT3, and p-STAT3 was assessed by immunohistochemical analysis of tissue microarrays for 275 ESCC patients who had undergone complete three-field lymphadenectomy. Spearman rank correlation tests were used to determine the relationships among protein expression, and Cox regression analyses were performed to determine the prognostic factors on overall survival (OS).
p-EGFR expression was correlated statistically with all of the other phosphorylated markers. Gender, N stage, and p-AKT1 expression were found to be independent prognostic factors for OS. Increased expression of p-AKT1 was associated with decreased patient survival. EGFR and p-EGFR expression was not significantly associated with patient survival.
Activation of AKT1 was associated with poor prognosis in ESCC.
Journal of Experimental & Clinical Cancer Research 09/2015; 34(1):95. DOI:10.1186/s13046-015-0212-z · 4.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lung squamous cell carcinoma (SQCC) accounts for about 30% of all lung cancer cases. Understanding of mutational landscape for this subtype of lung cancer in Chinese patients is currently limited. We performed whole exome sequencing in samples from 100 patients with lung SQCCs to search for somatic mutations and the subsequent target capture sequencing in another 98 samples for validation. We identified 20 significantly mutated genes, including TP53, CDH10, NFE2L2 and PTEN. Pathways with frequently mutated genes included those of cell-cell adhesion/Wnt/Hippo in 76%, oxidative stress response in 21%, and phosphatidylinositol-3-OH kinase in 36% of the tested tumor samples. Mutations of Chromatin regulatory factor genes were identified at a lower frequency. In functional assays, we observed that knockdown of CDH10 promoted cell proliferation, soft-agar colony formation, cell migration and cell invasion, and overexpression of CDH10 inhibited cell proliferation. This mutational landscape of lung SQCC in Chinese patients improves our current understanding of lung carcinogenesis, early diagnosis and personalized therapy.
[Show abstract][Hide abstract] ABSTRACT: This study was designed to identify the prevalence of BRAF mutations in Chinese patients with lung adenocarcinoma, and to reveal the association between BRAF mutations and clinicopathological characteristics in these patients.
From October 2007 to February 2013, patients with newly diagnosed primary lung adenocarcinoma were detected for mutations in BRAF, EGFR, KRAS, HER2 and ALK. Clinicopathological characteristics, including sex, age, TNM stage, tumor differentiation, smoking status, histological subtypes, and survival information were analyzed.
Of 1358 patients with lung adenocarcinoma, 20 patients were harboring BRAF mutations, including five BRAF V600E mutations and 15 BRAF non-V600E mutations. Among these, BRAF N581I and BRAF G593S were newly reported. BRAF mutations were associated with smoking status (odds ratio 3.28; 95 % CI 1.33-8.08; p = 0.008). In patients less than 60 years of age, BRAF mutations tended to have poor differentiation in tumor samples (70.0 vs. 35.1 %; p = 0.014), and were more likely to relapse (70 vs. 28 %; p = 0.008). A significant difference was found in relapse-free survival (RFS) between BRAF mutations and other mutations, but not in overall survival.
The prevalence of BRAF mutations in Chinese patients with lung adenocarcinoma was approximately 1.5 %. BRAF mutations were more frequent in current smokers. Patients harboring BRAF mutations had a higher rate of recurrence and worse RFS compared with other patients.
Annals of Surgical Oncology 07/2015; DOI:10.1245/s10434-015-4640-y · 3.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Thyroid transcription factor 1 (TTF1) is a master regulator of pulmonary differentiation that is downregulated in a subset of lung adenocarcinoma, of which the clinicopathologic characteristics were not fully clarified.
One thousand forty-two lung adenocarcinoma patients who underwent surgery were investigated for clinic characteristics, histologic subtyping, and spectrum of well-identified driver mutations. TTF1 expression was correlated with these clinicopathologic factors and survival.
Compared with TTF1 positive (TTF1+) patients, the 133 negative individuals (12.8%, TTF1-) were more likely to be male (p = 0.006) and heavy smokers (p = 0.002) who had larger tumor size (p < 0.001) and more advanced disease stage (p < 0.001). TTF1- presented more in solid and invasive mucinous-predominant carcinomas (both p < 0.001), whereas TTF1+ was identified in 100% patients with adenocarcinoma in situ, minimally invasive and lepidic-predominant adenocarcinomas. The TTF1- tumors harbored the known driver mutations in significantly low frequency compared with TTF1+ adenocarcinomas (57.8% versus 78.1%, p < 0.001), especially in epidermal growth factor receptor (EGFR) mutations (37.6% versus 60.7%, p < 0.001). There was no significant difference in recurrence-free survival between the TTF1- and TTF1+ patients, either for the whole cohort or stratified by pathologic stage, or among the driver mutation-defined subsets. However, recurrence of multiple metastases was more likely to occur in patients with TTF1- adenocarcinomas (88.1% versus 32.4%, p < 0.001). Multivariate analysis revealed that TTF1- -independently predicted both poor postrecurrence survival (hazard ratio = 1.664; 95% confidence interval , 1.097-2.524; p = 0.017) and unfavorable overall survival (hazard ratio = 1.553; 95% confidence interval , 1.013-2.381; p = 0.043).
TTF1- correlated with solid and invasive mucinous subtypes of lung adenocarcinoma and lower frequency of EGFR mutations. It defines a subgroup of lung adenocarcinomas with unfavorable outcomes.This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 07/2015; 10(10). DOI:10.1097/JTO.0000000000000626 · 5.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although over-expression of hepatocyte growth factor (HGF) and neuregulin-1 (NRG1) are important mechanisms involved in acquired drug-resistance in many cancers, few reports have evaluated their clinicopathologic features and prognostic significance. The aim of our study was to investigate protein expressions of HGF and NRG1 in lung adenocarcinomas and their association with clinicopathologic parameters, oncogenic mutations, and the prognosis.
HGF and NRG1 protein tumor/stroma expressions were evaluated by immunohistochemistry (IHC) in 115 surgically resected lung adenocarcinomas and were correlated with clinicopathologic and molecular variables including tumor size, tumor node metastasis stage, differentiation, oncogenic mutations (EGFR, KRAS, HER2, BRAF) and ALK fusions, relapse-free survival, and overall survival.
Positive IHC HGF tumor and stroma staining were found in 49 (42.61%) and 12 (10.43%) cases, respectively, while positive IHC NRG1 tumor and stroma staining were found in 56 (48.70%) and eleven (9.57%) cases, respectively. Dual positive IHC HGF and NRG1 tumor staining was 12.17%. EML4-ALK fusion more significantly existed in HGF-tumor positive samples (P=0.03), positive NRG1 protein stroma expression was significantly associated with male sex (P=0.04), while HGF and NRG1 dual tumor-positive mainly existed in the tumor size >3 cm group (P=0.0231). No significant clinically prognostic difference was found between patients with HGF/NRG1-positive expression and those with HGF/NRG1-negative expression.
This study represents the first comprehensive analysis of HGF and NRG1 tumor and stroma expressions in patients with surgically resected lung adenocarcinomas. Our molecular data, in conjunction with clinical and pathological features, as well as their effects on survival indicated to us that patients with HGF- and NRG1-negative expression tended to have better survival, but these results probably did not warrant these markers to be indicators of poor prognosis.
OncoTargets and Therapy 05/2015; 8:1185-91. DOI:10.2147/OTT.S78116 · 2.31 Impact Factor
[Show abstract][Hide abstract] 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.
Thoracic Cancer 03/2015; 6(3). DOI:10.1111/1759-7714.12240 · 0.90 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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; 141(5). DOI:10.1007/s00432-014-1878-x · 3.08 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: We performed this analysis to distinguish the differences in two subtypes of lung invasive mucinous adenocarcinoma (IMA) with different kinds of morphological performances, in clinicopathological and molecular features, as well as prognosis.
On the basis of morphological performance, we divided lung IMAs into two subgroups, mucus-in-cell adenocarcinoma (MICA) and mucus-out-of-cell adenocarcinoma (MOCA). We investigated differences in clinicopathological characteristics, recurrence-free survival (RFS), overall survival (OS), and a spectrum of well-identified driver-gene mutations, including EGFR, KRAS, HER2, BRAF, ALK, ROS1, and RET, between the two subgroups.
Of 1,699 lung adenocarcinomas, 148 were identified as IMAs (97 MICAs and 51 MOCAs). The MICA patient group had significantly better RFS than did the MOCA group (39.4 months versus 33.0 months, respectively, log rank P=0.020) and significantly better OS (54.2 months versus 45.1 months, log rank P=0.034). There were no differences in RFS and OS between those with IMAs and those with mucus-negative adenocarcinomas. The frequency of the EGFR gene mutation was significantly higher in MOCAs than in MICAs (P<0.001). In contrast, the KRAS gene had a significantly higher mutational frequency in MICAs (P=0.01). MOCAs also had a significantly higher incidence of lymph-node metastasis (P<0.05).
To our knowledge, this study represents the first comparison of clinical features, molecular alterations, and prognosis in morphological subgroups of lung IMAs. Clinical and pathological features in conjunction with molecular data indicate that IMA should be divided into different subgroups.
OncoTargets and Therapy 11/2014; 7:2127-2132. DOI:10.2147/OTT.S70984 · 2.31 Impact Factor
[Show abstract][Hide abstract] 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.
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.
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 · 3.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction:
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.
Thirty-six resected lung adenocarcinomas from young patients under 40 years old were analyzed concurrently for mutations in EGFR, KRAS, HER2, BRAF, AKT1, ALK, RET, TP53 and LKB1 and enrolled as the younger group. Their molecular and clinicopathologic characteristics were compared with those of 87 adenocarcinoma cases from patients above 40 years old which were collected as the older group.
The comparable overall survival (OS) (P=0.942), more early adenocarcinomas (P=0.033), more wedge resections (P<0.001) and fewer smokers (P=0.004) were seen in the younger group, when compared with the clinicopathologic characteristics in the older group. Nineteen EGFR mutations (52.8%), 3 KRAS mutations (8.3%), 2 EML4-ALK fusions (5.6%) and 1 KIF5b-RET fusion (2.8%) were identified in the younger group. The difference of oncogenic mutations between the two groups was statistically insignificant (P=0.396). Twenty-six TP53 mutations (72.2%) and 4 LKB1 mutations (11.1%) were found in the younger group. When compared with the old patients, young patients showed a higher prevalence of TP53 mutations (P<0.001) and a comparable prevalence of LKB1 mutations (P=0.951).
The youthful lung cancer unequivocally presented the distinct clinicopathologic characteristics including more early adenocarcinomas and fewer smokers. It showed the similar oncogenic characteristics and higher prevalence of TP53 mutations compared with the older counterpart.