Inter-subtype recombination is the main force for the complexity of HIV-1 genetic diversity,which increases the difficulty of preventing HIV-1 infection and administering antiretroviral therapy for people living with HIV.To date,143 circulating recombinant forms(CRFs)have been re-ported globally,43 of which were identified in China.1 Moreover,HIV-1 strains that are produced by second-gen-eration combinations,including unique recombinant forms and CRFs,such as CRF105_0108,CRF123_0107,and CRF134_0185,have been commonly reported in recent years.The present study identified a novel second-gener-ation recombinant form of HIV-1 comprising CRF07_BC and subtype C and designated CRF144_07C.To our knowledge,this was the first report of HIV CRFs comprising CRF07_BC and subtype C,further indicating the complexity of HIV genetic diversity in China.

Abstract Background The eighth edition of the American Joint Committee on Cancer (AJCC) staging system for lung cancer adopts new criteria for tumor size, and for determining pTis, pT1a(mi), and pT1a. The latter is based on the size of stromal invasion. It is quite challenging for lung pathologists. Methods All patients who had undergone surgical resection for pulmonary adenocarcinoma (ADC) at Chung Shan Medical University Hospital between January 2014 and April 2018 were reviewed, and restaged according to the eighth AJCC staging system. The clinical characteristics and survival of patients with tumor stage 0 (pTis), I or II were analyzed. Results In total, 376 patients were analyzed. None of the pTis, pT1a(mi), or pT1a tumors recurred during the follow‐up period up to 5 years, but pT1b, pT1c, pT2a, and pT2b tumors all had a few tumor recurrences (p < 0.0001). In addition, 95.2%, 100%, and 77.5% of pTis, pT1a(mi), and pT1a tumors, respectively, had tumor sizes ≤1.0 cm by gross examination. All pTis, pT1a(mi), and pT1a tumors exhibited only lepidic, acinar, or papillary patterns histologically. Conclusions This study demonstrated excellent survival for lung ADC patients with pTis, pT1a(mi), and pT1a tumors when completely excised. To reduce the inconsistencies between pathologists, staging lung ADC with tumors of ≤1 cm in size grossly as pTis, pT1a(mi), or pT1a may not be necessary when the tumors exhibit only lepidic, acinar, or papillary histological patterns. A larger cohort study with sufficient follow‐up data is necessary to support this proposal.

Hepatocellular carcinoma (HCC) is the main threat for the patients infected with hepatitis B virus (HBV), but the oncogenic mechanism of HBV-related HCC is still controversial. Previously, we have found that several HBV surface gene (HBS) non-sense mutations are oncogenic. Among these mutations, sW182* was found to have the most potent oncogenicity. In this study, we found that Carbonic Anhydrase X (CA10) level was specifically increased in sW182* mutant-expressing cells. CA10 overexpression was also associated with HBS nonsense mutation in HBV-related HCC tumor tissues. Transformation and tumorigenesis assays revealed that CA10 had significant oncogenic activity. In addition, CA10 overexpression resulted in dysregulation of apoptosis-related proteins, including Mcl-1, Bcl-2, Bcl-xL and Bad. While searching for the regulatory mechanism of CA10, miR-27b was found to downregulate CA10 expression by regulating its mRNA degradation and its expression was decreased in sW182* mutant cells. Moreover, CA10 overexpression was associated with down-regulation of miR-27b in human HBV-related HCC tumor tissues with sW182* mutation. Therefore, induction of the expression of CA10 through repression of miR-27b by sW182* might be one mechanism involved in HBS mutation-related hepatocarcinogenesis.

Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC). Previous studies have identified recurrent nonsense mutations in the HBV large S (LHBs) gene from the liver from HBV core antigen-positive HCC patients. These nonsense mutants have been shown to be oncogenic in mouse xenograft models using a mouse embryonic fibroblast cell line. Here, we expressed in a liver cell line Huh-7 a carboxy terminally truncated protein from a nonsense mutant of the LHBs gene, sW182* (stop codon at tryptophane-182). Although the sW182* protein appeared not to be very stable in the cultured liver cells, we confirmed that the protein can be highly expressed and retained for a prolonged period of time in the hepatocytes in the mouse liver, indicating its stable nature in the physiological condition. In the Huh-7 cells, the sW182* mutant downregulated tumor suppressors p53 and Smad4. This downregulation was reversed by a proteasome inhibitor MG132, implying the involvement of proteasome-based protein degradation in the observed regulation of the tumor suppressors. On the other hand, we found that c-Jun activation domain-binding protein 1 (Jab1) physically interacts with the sW182*, but not wild-type LHBs. RNA interference (RNAi) of Jab1 restored the levels of the downregulated p53 and Smad4. The sW182* mutant inhibited the promoter activity of downstream target genes of the tumor suppressors. Consistently, Jab1 RNAi reversed the inhibition. These results suggest that the LHBs nonsense mutant antagonizes the tumor suppressor pathways through Jab1 in the liver contributing to HCC development.

With the increasing number of medical students and scattered host hospitals, the traditional clinical internship management system has been falling behind. Thus, we have independently developed a new clinical practice management system based on the browser/server structure. We aim to evaluate the efficacy of the new medical management system on the quality of the internship and survey the users' satisfaction. This study was conducted on the students of Second Clinical Medical College of Southern Medical University, including 672 interns (non-user group) who had not used the system and 315 users (user group). We analyzed the scores of their theoretical knowledge and clinical skills before and after the internship, which served as the quantitative standards for evaluating the efficacy of the system. User satisfaction surveys were also conducted, including by interns, clinical teachers, and teaching administrators. An analysis of scores showed that the user group had more significant improvement in both clinical knowledge and skills than the non-user group after the internship. Significant improvement was found in the user group, while there was a slight difference in the non-user group. A total of 310 students responded to the satisfaction questionnaires effectively, most of whom agreed with the system's benefits of learning theoretical knowledge (98.1%, n = 304) and clinical skills (93.9%, n = 291). Additionally, 115 clinical teachers and 27 teaching administrators were selected using a random sampling method for the survey. The results showed that 96.3% of the teachers considered the system to be helpful for improving teaching quality, and 92.6% administrators thought it was useful for implementing management. Over 90% of the participants in the 3 user groups reported a strong satisfaction of the system. With high level of user satisfaction, this system helps to strengthen the management for interns and improves the medical knowledge and skills of interns. Hence, it could be widely used in medical colleges and even in other fields.

Carboxypeptidase E (CPE), a prohormone processing enzyme, is a 476- amino acid protein with a signal peptide in its N-terminus and is expressed in the nervous and the endocrine systems. Recent evidence indicate CPE plays various non-enzymatic roles in the endocrine and nervous systems and in various cancers. Besides wild type (WT) CPE, a 40-kDa CPE protein that localizes in the nucleus and cytoplasm has been described in embryonic mouse brain. In this study we have cloned this CPE variant encoding the 40kDa CPE-ΔN protein from human cancer cells. RACE assay and sequence analysis confirmed existence of this CPE variant mRNA, which has 198 nucleotides removed within the first exon and 589 nucleotides from the 3’-UTR, respectively, compared to WT-CPE mRNA. Bioinformatic analysis revealed that this CPE variant mRNA has a shortened open reading frame, which starts coding from the 3rd ATG relative to WT-CPE mRNA and encodes a 40kDa N-terminus truncated CPE protein. RT-PCR and Western blot analysis showed that 40kDa CPE-ΔN is expressed in multiple cancer cell lines and tumor tissues. Overexpression of this 40kDa CPE-ΔN variant up-regulated expression of multiple metastatic genes encompassing different signaling pathways, suggesting potentially an important role of CPE-ΔN in tumor metastasis.

目的:综述色瑞替尼治疗间变性淋巴瘤激酶(ALK)阳性非小细胞肺癌(NSCLC)的研究概况.方法:以"非小细胞肺癌""间变性淋巴瘤激酶抑制剂""色瑞替尼""Non-small cell lung cancer""Ceritinib"作为关键词,查阅中国知网、PubMed数据库截止至2017年6月的文献,就色瑞替尼治疗ALK阳性NSCLC的药效学、药动学、临床疗效、安全性等的研究进行整理分析和归纳总结.结果与结论:共检索到英文文献1464篇,中文文献127篇,其中有效文献27篇.色瑞替尼为ALK的高效抑制剂,能有效克服第一代ALK克唑替尼的部分耐药突变;其多次给药后呈非线性药动学特征,不建议与细胞色素P4503A的强抑制剂和诱导剂联用.与化疗和克唑替尼比较,色瑞替尼显著延长了患者的中位无进展生存期与总生存期,其透过颅内浓度高于克唑替尼;最常报道的不良事件是腹泻、恶心、呕吐、腹痛和食欲下降,通常为1~2级,可通过降低剂量减少不良事件的发生,较少引起治疗中止.色瑞替尼可作为ALK阳性、经克唑替尼治疗后疾病进展或不能耐受的晚期NSCLC患者的治疗方案.

Rationale: Kennedy disease (KD) is also known as spinal bulbar muscular dystrophy. As KD has similar symptoms with most neuromuscular diseases, so it is difficult to make a rapid diagnosis clinically. Patient concerns: We report a case of a 43-year-old male with progressive limb proximal weakness without family history. Physical examination showed gynecomastia, erectile dysfunction, bilateral tendon reflex and quadriceps weakness, and tongue muscle atrophy. Diagnoses: Laboratory examination found increased creatine kinase, impaired glucose tolerance, and abnormal lactic acid values. There was no mutation or copy number variant in SMN1 gene and related mitochondrion genes tested, even with the use of multiplex ligation probe- dependent amplification technique. Diagnosis was confirmed with genetic analysis which displayed trinucleotide CAG (glutamine)- repeat expansion in the androgen-receptor gene. Interventions and Outcomes: The patient achieved good prognosis with symptomatic treatment after diagnosis. Lessons: To diagnose KD, clinicians should pay more attention to differentiate KD and myasthenia gravis, mitochondrial myopathy, and amyotrophic lateral sclerosis. Gene analysis was the key in detecting this rare confusing disease in the patient.

With the clinical promotion of precision medicine and individualized medical care, molecular targeted medicine has been used to treat non-small cell lung cancer (NSCLC) patients and proved to be significantly effective. Anaplastic lymphoma kinase (ALK) inhibitor is one of the most important specific therapeutic agents for patients with ALK-positive NSCLC. It can extend the survival of patients. However, resistance to the ALK inhibitor inevitably develops in the application process. So, the real-time resistance surveillance is particularly important, and liquid biopsy is one of the most potential inspection methods. Circulating tumor cells, circulating free tumor DNA and exosome in body fluid are used as the main detection biomarkers to reflect the occurrence of resistance in real time through sequencing or counting and then to guide the follow-up treatment.

Afatinib which is orally administered is an irreversible inhibitor of the epidermal growth factor receptor (EGFR) family tyrosine kinase.The LUX-Lung 7 trial has shown that in the first-line treatment of patients with advanced EGFR-mutant lung adenocarcinoma,afatinib could significantly improve the progression-free survival (PFS) and the time to treatment failure (TTF) as compared with gefitinib,but failed to achieve clinical benefit for the overall survival (OS).As compared with pemetrexed plus cisplatin regimen (LUX-Lung 3 trial) and gemcitabine plus cisplatin regimen (LUX-Lung 6 trial),afatinib could significantly prolong the PFS,but not the OS.However,it is worth noting that both LUX-Lung 3 trial and LUX-Lung 6 trial have shown that in the subgroup of patients with 19 exon deletion mutation of EGFR,the OS was significantly prolonged when receiving afatinib treatment versus chemotherapy.In addition,in the second-line treatment of advanced squamous-cell lung carcinoma,afatinib has shown to significantly prolong the PFS and OS as compared with erlotinib,regardless of EGFR mutation status (LUX-Lung 8 trial).Side effects of afatinib treatment in patients with NSCLC could be prevented by lowering the dose.In conclusion,afatinib can be used in the first-line treatment for patients with EGFR-mutant advanced NSCLC,and also can be used in the second-line treatment of squamous-cell lung carcinoma with progression after platinum-based chemotherapy.

To explore the relationship between neutrophil-to-lymphocyte ratio (NLR) and diabetic peripheral neuropathy (DPN) in type 2 diabetes mellitus.A total of 557 newly diagnosed Type 2 Diabetes Mellitus (T2DM) patients were recruited, including 397 T2DM patients without complication (DM group) as well as 160 T2DM patients complicated with DPN (DPN group). Student t test, Mann-Whitney U test, or (2) test was applied to the data of the 2 groups, including the levels of neutrophils and lymphocytes as well as the NLR values of peripheral blood and other biochemistry indexes; Pearson correlation analysis was used to calculate the correlation of NLR and detected factors; risk factors of DPN were estimated via logistic regression analysis and multivariate analysis.The values of triglyceride (TG), neutrophils, fasting insulin, urinary albumin, and 2 hour postglucose in DPN group were significantly higher than those of the DM group, whereas the number of lymphocytes of DPN group was considerably lower than that of the DM group (P<.05 respectively); NLR values were remarkably higher in DPN group compared with those of DM group (2.580.50 vs 2.18 +/- 0.61, P<.001); logistic regression analysis showed that NLR (P=.002, OR=4.960, 95% CI=1.843-13.349) was a risk factor of DPN. Multivariate logistic regression analysis showed that DPN was independently related to NLR (P=.002, OR=4.960, 95% CI=1.843-13.349). The ROC curve analysis confirmed that the optimal cut-off point, specificity, and sensitivity in diagnosing DPN by NLR were 2.13%, 48.1%, and 81.3% respectively.Our results showed that NLR is significantly correlated with DPN, which suggested that NLR may be an independent risk factor of DPN.

Background: The outcome of colon cancer patients without lymph node metastasis is heterogeneous. Searching for new prognostic markers is warranted.Methods: One hundred twenty stage I-II colon cancer patients who received complete surgical excision during 1995-2004 were selected for this biomarker study. Immunohistochemical method was used to assess p53, epidermal growth factor receptor, MLH1, and MSH2 status. KRAS mutation was examined by direct sequencing.Results: Thirty three patients (27.5%) developed metachronous metastasis during follow up. By multivariate analysis, only female gender (p = 0.03), high serum carcinoembryonic antigen (CEA) level (>= 5 ng/ml) (p = 0.04), and MLH1 overexpression (p = 0.003) were associated with the metastasis group. The 5-year-survival rate were also significantly lower for female gender (71.7% versus 88.9%, p = 0.025), high CEA level (64.9% versus 92.4%, p < 0.001), and MLH1 overexpression (77.5% versus 94.4%, p = 0.039). In contrast, MSH2 overexpression was associated with better survival, 95.1% versus 75.5% (p = 0.024).Conclusions: The reversed prognostic implications in the overexpression of MLH1 and MSH2 for stage I-II colon cancer patients is a novel finding and worthy of further confirmation.

Non-small-cell lung cancer (NSCLC) is a common disease threatening the health of humankind. It has a low survival rate and a poor prognosis. Under normal circumstances, tumor infiltrating lymphocytes (TILs) play the main role in the antitumor process, but studies in recent years have found that NSCLC is capable of releasing various immunosuppressive factors, inducing the TILs to exhibit high expression of immune inhibitory receptors and relevant immunosuppressive factors. They can not only activate their own signal pathways but also block those of TILs, which causes inefficiency of tumor destruction. Researchers have now developed targeted drugs that specifically bind to immunosuppression receptors. By blocking signal transmission of immune inhibitory receptors, restraint on T lymphocytes can be released to recover antitumor role. Further research and understanding of the immunosuppression signal pathways of NSCLC are of significant importance to promote the development of immune-targeted drugs and the formulation of new treatment plans. This paper summarizes the immunosuppressive mechanisms of multiple important and newly discovered immune inhibitory receptors on T lymphocytes and immunosuppressive factors released by NSCLC cells, and their influence on patients' survival rate and prognosis. Further laboratory and clinical studies on immune-targeted drugs for primary NSCLC are needed to provide more evidence.

Tumor recurrence and metastasis are the major causes of death for hepatocellular carcinoma (HCC) patients who are able to receive curative resection. Identifying the predicting biomarkers for tumor recurrence would improve their survival. RNA extracted from fresh frozen tumors and adjacent non-tumor liver tissues of 120 HCC patients were obtained from Taiwan Liver Cancer Network (TLCN) in year 2010 for determination of the carboxypeptidase E (CPE) expression level (including its splicing mutant CPE-ΔN) in the tumor tissue (T) and paired non-tumor liver tissue (N) by real-time quantitative polymerase chain reaction. All patients were male, had chronic hepatitis B virus infection, were in the early pathology stage, and received curative resection. The T/N ratio of the CPE expression level was correlated with the updated survival data from TLCN in 2015. The CPE expression level in the 120 HCC patients was divided into three groups according to the T/N ratio: <1, ≥1 and ≤2, and >2, respectively. By multivariate analyses, the recurrence-free survival (RFS) was only significantly associated with the pathology stage and the CPE expression level. For overall survival (OS), only the CPE expression level was the significant prognostic factor. The CPE expression level was also significantly correlated with the tumor recurrence for both stage I (p = 0.0106) and stage II patients (p = 0.0006). The CPE mRNA expression level in HCC can be a useful biomarker for predicting tumor recurrence in HCC patients who are in the early pathology stage and able to receive curative resection.

Epidermal growth factor receptor (EGFR) gene mutations are strongly associated with lung adenocarcinoma and favorable response to EGFR tyrosine kinase inhibitor. The mutated EGFR proteins (EGFRs) are hyper-phosphorylated and refractory to receptor down-regulation. To address the discrepancy between hyper-phosphorylation and lack of down-regulation of mutant EGFRs, we have examined the expression of EGFR negative regulators in non-small cell lung cancer (NSCLC) cell lines. We found that NSCLC cell lines expressing mutant EGFRs often had low expression of various negative regulators for EGFR. Among them, tumor suppressor CD82 was up-regulated by wild type (WT) EGFR but down-regulated by mutant EGFRs. Reconstitution of CD82 exerted stronger suppressive effects on mutant EGFRs than on WT EGFR. Active exportation of CD82 through the exosome was one of the mechanisms involved in achieving the overall CD82 down-regulation in mutant EGFR-expressing lung cancer cell lines. Over-expression of mutant EGFR protein frequently occurred in the lung cancer tissues of mutant EGFR-transgenic mice and also associated with CD82 down-regulation. Immunoblot analyses on the tumor tissues from 23 lung adenocarcinoma patients (12 with WT EGFR, and 11 with mutant EGFRs) also identified significantly stronger down-regulation of CD82 in tumors with mutant EGFRs than WT. Our data indicate that CD82 down-regulation could be a critical step involved in the EGFR over-expression and the stronger tumorigenic activity triggered by EGFR mutations. Up-regulation of the CD82 level may become a promising new treatment strategy for lung adenocarcinoma.

Background & Aims The correlation between chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) has been well-established. But the roles of viral factor remain uncertain. Only HBV X gene and nonsense mutations of S gene (C-terminal truncation of HBV surface protein) have been demonstrated to have transforming activity. Whether they play a significant role in hepatocarcinogenesis is still uncertain. Methods Twenty-five HBV-related HCC patients were positive for hepatitis B core antigen (HBcAg) in the cancerous parts of their HCC liver tissues by immunohistochemistry studies, and had available tissue for whole HBV genome sequence analysis. The results were compared with 25 gender and age-matched HBcAg negative HCCs. Plasmids encoding HBV S gene nonsense mutations identified from HBcAg (+) HCC tissue were constructed to investigate their cell proliferation, transformation activity and the oncogenic potentials by xenograft study and in vivo migration assay. Results HBcAg (+) HCC patients were significantly associated with cirrhosis and small tumor size (≦2 cm) when compared with HBcAg (−) HCC patients. Southern blot analyses revealed freely replicative forms of HBV in the cancerous parts of HBcAg(+) HCC. Three nonsense mutations of S gene (sL95*, sW182*, and sL216*) were identified in the HBcAg(+) HCC tumor tissues. sW182* and sL216* were recurrently found in the 25 HBcAg (−) HCC tumor tissue, too. Functional studies of the above 3 non-sense mutations all demonstrated higher cell proliferation activities and transformation abilities than wild type S, especially sW182*. Tumorigenicity analysis by xenograft experiments and in vitro migration assay showed potent oncogenic activity of sW182* mutant. Conclusions This study has demonstrated potent oncogenic activity of nonsense mutations of HBV S gene, suggesting they may play an important role in hepatocarcinogenesis.

The nonsense mutations of the hepatitis B virus (HBV) surface (S) gene have been reported to have oncogenic potential. We have previously identified several transforming nonsense mutations of the HBV S gene from hepatocarcinoma (HCC) patients. Among them, the sW182* mutant (the stop codon for tryptophan 182) showed the most potent oncogenicity in a mouse xenograft model using stably transfected mouse fibroblast cells. This study is aimed at understanding the molecular mechanisms leading to the oncogenic activity of the sW182* mutant. A gene expression microarray in combination with gene set enrichment analysis (GSEA) revealed differentially expressed gene sets in the sW182* cells, including those related to cell-cycle regulation, deoxyribonucleic acid repair, and genome instability. Of the differentially expressed genes, the transforming growth factor-β-induced (TGFBI) gene was further validated to be dysregulated in the sW182* cells. This dysregulation was accompanied by hypermethylation of the TGFBI promoter. The level of cyclin D1, a negatively regulated TGFBI target, was highly elevated in the sW182* mutant cells, which is consistent with the potent oncogenicity. Furthermore, frequent abnormal mitosis and multinucleation were observed in the mutant cells. Exogenous expression of TGFBI alleviated the oncogenic activity of the sW182* cells. In human HBV-related HCC cancerous tissue, expression of TGFBI was downregulated in 25 of the 55 (45%) patients examined, suggesting that TGFBI dysregulation could occur in HBV-related HCC development in some cases. These results suggest that dysregulation of TGFBI is involved in the oncogenic activity of the sW182* mutant of the hepatitis B virus S gene.

Background Recently Echinoderm microtubule-associated protein-like 4- anaplastic lymphoma kinase (EML4-ALK) fusion gene has become an important biomarker for ALK tyrosine kinase inhibitor (crizotinib) treatment in NSCLC. However, the best detection method and the significance of EML4-ALK variant types remain uncertain. Methods Reverse transcriptase-polymerase chain reaction (RT-PCR), fluorescence in Situ hybridization (FISH) and Immunohistochemical (IHC) stain were performed on tumor tissues of 312 NSCLC patients for detection of ALK rearrangements. Mutation analyses for EGFR and KRAS genes were also performed. Results Thirteen of the 312 patients (4.17%) had ALK rearrangements detected by RT-PCR. If RT-PCR data was used as the gold standard, FISH tests had a low sensitivity (58.33%), but very good specificity (99.32%). IHC stain had better sensitivity (91.67%) than FISH, but lower specificity (79.52%), when the cut off was IHC2+. All of the 8 patients with high abundance of EML4-ALK positive cells in tumor tissues (assessed by the signal intensities of the RT-PCR product), were also have high expression of ALK protein (IHC3+), and positive for FISH, except one failed in FISH. Variants 3a+3b (4/5, 80%) of EML4-ALK fusion gene were more common to have high abundance of EML4-ALK positive cells in tumor tissues than variant 1 (1/3, 33.3%). Meta-analysis of the published data of 2273 NSCLC patients revealed that variant 3 (23/44, 52.3%) was the most common type in Chinese population, while variant 1 (28/37, 75.7%) was most common in Caucasian. Conclusions Among the three detection methods, RT-PCR could detect not only the presence of EML4-ALK fusion gene and their variant types, but also the abundance of EML4-ALK positive cells in NSCLC tumor tissues. The latter two factors might affect the treatment response to anti-ALK inhibitor. Including RT-PCR as a diagnostic test for ALK inhibitor treatment in the prospective clinical trials is recommended.

Background:Recently the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene with transforming activity was identified in non-small cell lung cancer (NSCLC).In addition, NSCLC patients with the EML4-ALK fusion gene had a dramatic response and longer progression free survival after ALK inhibitor treatment than those without this fusion gene.However, the incidence and clinical and molecular characteristics of the EML4-ALK fusion gene in NSCLC patients of Taiwan are still unclear. Methods:Sixty-four fresh frozen tumor specimens were obtained from the tissue bank of Chang Gung Memorial Hospital for RNA extraction and EML4-ALK fusion gene detection.Paraffin sections of lung tumors from all of these patients were available and were analyzed for ALK protein expression by immunohistochemical (IHC) study.The results were correlated with clinical and molecular biomarkers. Results:Three of the 64 tumors (4.7%) had the EML4-ALK fusion gene.Two were adenocarcinomas, and one was adenosquamous carcinoma.Twenty patients with non-squamous cell carcinomas had epidermal growth factor receptor (EGFR) mutations, so the EML4-ALK fusion gene was found in 14.3% of EGFR wild type non-squamous cell carcinomas.Two tumors were variant 3 (3a+3b with 3b predominant) and had strong staining (3+) for ALK by IHC stains.One tumor was variant 1 and had moderate staining (2+) for ALK.None of the ALK wild type tumors had strong staining for ALK.When compared with other clinical and molecular features, only the IHC stain for ALK was significantly correlated with the EML4-ALK fusion gene (p = 0.0002).Conclusions: ALK overexpression detected by IHC study could be a promising detection method for the EML4-ALK fusion gene and is worth further confirmation with more samples.