共查询到20条相似文献,搜索用时 31 毫秒
1.
Aims
EGFR mutations now guide the clinical use of EGFR-targeted therapy in lung cancer. However, standard EGFR mutation analysis requires a minimum amount of tumor tissue, which may not be available in certain situations. In this study, we combined a mass spectrometry genotyping assay (Sequenom) with a mutant-enriched PCR (ME-PCR) to detect EGFR mutations in free plasma DNA from patients with lung cancer.Method
DNAs were extracted from 31 plasma samples from 31 patients and analyzed by both methods for EGFR Exon 19 deletion and EGFR L858R mutation. Results in plasma DNA samples were compared with EGFR mutation status obtained in tumor DNA (18/31 EGFR mutant). The relationship of EGFR mutation status in tumor and/or plasma samples to overall survival was assessed.Results
The EGFR mutation status in plasma DNA was identical to the primary tumor in 61% of patients (19/31). By mass spectrometry genotyping, the plasma samples contained mutant DNA corresponding to 5/14 EGFR Exon 19 deletions and 3/4 EGFR L858R mutations previously diagnosed in the matched tumors. Two samples were positive in plasma DNA but negative in primary tumor tissue. Results were similar for samples studied by ME-PCR. For patients treated with erlotinib, overall survival was correlated with the presence of EGFR mutation in plasma and/or tumor tissue (p = 0.002), with the two patients positive only in plasma DNA showing responses and favorable outcomes.Conclusion
The detection of EGFR mutations in plasma DNA samples by mass spectrometry genotyping and ME-PCR is feasible. A positive EGFR result in plasma DNA has a high predictive value for tumor EGFR status and for favorable clinical course on EGFR-targeted therapy and could therefore be useful in guiding clinical decisions in patients with insufficient or unavailable tumor specimens. 相似文献2.
An Na Seo Tae-In Park Yan Jin Ping-Li Sun Hyojin Kim Hyun Chang Jin-Haeng Chung 《Lung cancer (Amsterdam, Netherlands)》2014
Objectives
Activating mutations in the epidermal growth factor receptor (EGFR) kinase domain are correlated with dramatic clinical responses in non-small cell lung cancer patients treated with EGFR-tyrosine kinase inhibitors (TKIs). The two most common EGFR mutations, representing 85–90% of EGFR mutations, are the E746_A750 deletion in exon 19 and the L858R point mutation in exon 21. We conducted this study to evaluate the suitability of mutation-specific antibodies that can detect E746_A750 deletion and L858R mutant EGFR proteins by immunohistochemistry (IHC).Materials and methods
In a cohort of consecutive patients with surgically resected lung adenocarcinomas (n = 240), mutant EGFR protein expression was assessed by IHC using specific antibodies (clone SP111 and SP125) to the 2 major forms of EGFR mutations. Immunoreactivity was scored as 0–3, and the results were compared with the EGFR-mutational status.Results
With a cutoff value of IHC 2+ for SP 111 (anti-EGFR E746_A750 del antibody) and SP 125 (anti-EGFR L858R antibody), both antibodies showed high specificity (99.0% and 89.7%, respectively) and sensitivity (70.6% and 80.4%, respectively). While cases with IHC scores of 3 using these 2 antibodies positively correlated with the EGFR-mutational status, cases with IHC scores lower than 3+ showed variable results regarding EGFR-mutational status.Conclusion
Although each antibody showed relatively high specificity, some EGFR-mutant cases were not detected by the mutation-specific antibodies. Various forms of exon 19 deletions, except E746_A750, were rarely detected by the mutant-specific antibody. Therefore, IHC-negative cases require further molecular analysis to confirm the presence of EGFR mutations. 相似文献3.
Gillian Ellison Emma Donald Gael McWalter Lucy Knight Lynn Fletcher James Sherwood Mireille Cantarini Maria Orr Georgina Speake 《Journal of experimental & clinical cancer research : CR》2010,29(1):132
Background
We have compared mutation analysis by DNA sequencing and Amplification Refractory Mutation System™ (ARMS™) for their ability to detect mutations in clinical biopsy specimens.Methods
We have evaluated five real-time ARMS assays: BRAF 1799T>A, [this includes V600E and V600K] and NRAS 182A>G [Q61R] and 181C>A [Q61K] in melanoma, EGFR 2573T>G [L858R], 2235-2249del15 [E746-A750del] in non-small-cell lung cancer, and compared the results to DNA sequencing of the mutation ''hot-spots'' in these genes in formalin-fixed paraffin-embedded tumour (FF-PET) DNA.Results
The ARMS assays maximised the number of samples that could be analysed when both the quality and quantity of DNA was low, and improved both the sensitivity and speed of analysis compared with sequencing. ARMS was more robust with fewer reaction failures compared with sequencing and was more sensitive as it was able to detect functional mutations that were not detected by DNA sequencing. DNA sequencing was able to detect a small number of lower frequency recurrent mutations across the exons screened that were not interrogated using the specific ARMS assays in these studies.Conclusions
ARMS was more sensitive and robust at detecting defined somatic mutations than DNA sequencing on clinical samples where the predominant sample type was FF-PET. 相似文献4.
Watanabe T Kobunai T Yamamoto Y Matsuda K Ishihara S Nozawa K Iinuma H Ikeuchi H Eshima K 《European journal of cancer (Oxford, England : 1990)》2011,47(13):1946-1954
Purpose
KRAS mutation is an important predictive marker in determining resistance to anti-Epidermal Growth Factor Receptor (EGFR) antibody therapies. In order to clarify whether not only KRAS related signalling pathways but also other signalling pathways are altered in patients with colorectal cancers (CRCs) with KRAS mutations, we examined the differences in the gene expression signatures between CRCs with and without KRAS mutation.Patients and methods
One-hundred and thirteen patients who underwent a surgical resection of a primary CRC were examined. KRAS mutational status was determined using the Peptide Nucleic Acid (PNA)-clamp real-time polymerase chain reaction (PCR) TaqMan assay. Gene expression profiles were compared between CRCs with and without KRAS mutation using the Human Genome GeneChip array U133.Results
Among 113 CRCs, KRAS mutations were present in 35 tumours (31%). We identified 30 genes (probes) that were differentially expressed between CRCs with and without KRAS mutation (False Discovery Rate (FDR), p < 0.01), by which we were able to predict the KRAS status with an accuracy of 90.3%. Thirty discriminating genes included TC21, paired-like homeodomain 1 (PITX1), Sprouty-2, dickkopf homologue 4 (DKK-4), SET and MYND domain containing 3 (SMYD3), mitogen-activated protein kinase kinase kinase 14 (MAP3K14) and c-mer Proto-oncogene tyrosine kinase (MerTK). These genes were related to not only KRAS related signalling pathway but also to other signalling pathways, such as the Wnt-signalling pathway, the NF-kappa B activation pathway and the TGF-beta signalling pathway.Conclusions
KRAS mutant CRCs exhibited a distinct gene expression signature different from wild-type KRAS CRCs. Using human CRC samples, we were able to show that there is crosstalk between the KRAS-mediated pathway and other signalling pathways. These results are necessary to be taken into account in establishing chemotherapeutic strategies for patients with anti-EGFR-refractory KRAS mutant CRCs. 相似文献5.
Soh J Toyooka S Aoe K Asano H Ichihara S Katayama H Hiraki A Kiura K Aoe M Sano Y Sugi K Shimizu N Date H 《International journal of cancer. Journal international du cancer》2006,119(10):2353-2358
The importance of epidermal growth factor receptor (EGFR) gene mutation has been recognized in nonsmall cell lung cancer (NSCLC), requiring the standardization of mutation screening system including the kind of samples. Here, we examined the EGFR mutation status in 61 pleural fluid samples from NSCLC cases using direct sequencing, nonenriched PCR, mutant-enriched PCR and peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp assay. The mutant-enriched PCR assay detected 16 mutant cases. Among them, the nonenriched PCR assay failed to detect 3 mutant cases. Regarding the discrepancy between mutant-enriched PCR and PNA-LNA PCR clamp assays, 3 cases of exon19-deletions were detected only by mutant-enriched PCR assay and no difference at the L858R mutation. There was no difference in results between direct sequencing and nonenriched PCR assay. We also correlated the EGFR mutation with clinical outcome of gefitinib-treated 29 cases. EGFR mutations were present in 10 cases, revealing 7 partial response and 3 no change (NC). In EGFR wild-type cases, 10 revealed NC and 9 progressive disease. The responders were significantly more frequent among the EGFR mutant cases than among the wild-type (p < 0.0001). Overall survival (p = 0.0092) and progression-free survival (p = 0.018) were significantly longer among the EGFR mutant cases than among the wild-type. In summary, we evaluated the utility of EGFR mutation screening in pleural fluid using 4 assays that showed some discrepancies arising from the designs of the assays. As clinical importance, the EGFR mutation status in pleural fluid can be a biomarker for the favorable outcome of gefitinib-treated NSCLC cases. 相似文献
6.
Anastasios Dimou Paul Grewe John Sidney Alessandro Sette Paul J. Norman Robert C. Doebele 《Journal of thoracic oncology》2021,16(1):104-112
IntroductionCancer-associated mutations have the potential to generate neoantigens and elicit CD8-positive T-cell–dependent adaptive immune responses. There are currently no reports of CD8-positive T-cells with specificity for neoepitopes generated by EGFR mutations, which are driver oncogenes in a subset of patients with lung cancer.MethodsWe used NETMHCpan 4.0 to identify putative protective human leukocyte antigen (HLA) class I allotypes that are predicted in silico to bind and present mutant EGFR-generated peptides on the basis of predefined criteria. We associated the presence or absence of these alleles with clinical outcomes in patients from The Cancer Genome Atlas with lung adenocarcinoma.ResultsWe identified 12 HLA class I alleles that fulfilled the predefined criteria for being protective for EGFR p.L858R and six for EGFR p.E746_A750del, the two most common EGFR mutations in lung cancer. We validated the in silico predictions for peptide-HLA allele binding in vitro. A third (12 of 36) of patients with mostly early stage lung adenocarcinoma in The Cancer Genome Atlas with either EGFR p.L858R or EGFR p.E746_A750del had at least one protective allele in their host genomes. More importantly, patients with protective alleles exhibited better disease-free (hazard ratio: 0.20, 95% confidence interval: 0.05–0.78) and overall survival (hazard ratio: 0.13, 95% confidence interval: 0.02–0.64), and this effect was independent of the EGFR mutation type, stage, age, and sex.ConclusionsOur data revealed that clinical outcomes were improved in patients with EGFR mutation–positive lung adenocarcinoma who harbored protective HLA class I alleles. Thus, immunity with specificity for mutant EGFR is possible in a subset of patients with early stage lung cancer and portends a better prognosis. 相似文献
7.
Fusi A Berdel R Havemann S Nonnenmacher A Keilholz U 《European journal of cancer (Oxford, England : 1990)》2011,47(13):1971-1976
Purpose
Characterisation of circulating melanoma cells (CMC) for BRAF status can provide a strategy for non-invasive serial genotype monitoring in patients receiving BRAF inhibitors. We aimed to establish a method for BRAF mutation analysis at CMC level and we applied it in a cohort of CMC-positive patients.Methods
We established a sensitive method for detection of BRAF mutations at codon 600 in whole blood samples of patients with melanoma, positive for presence of CMC. The method based on selective cleavage of wild-type sequences by taking the advantage of the presence of a TspR1 enzyme restriction site located at the site of mutation.Results
In a serial dilution experiment spiking BRAF mutated cDNA into BRAF wild-type cDNA the method allowed to detect mutated cDNA till a dilution of 1:104. Peripheral blood (PB) samples resulting positive for CMC and matched tissue specimens from 21 different AJCC stage IV melanoma patients were analysed. A 91% (19/21) correspondence between BRAF status in tissue and PB specimens was observed. In a patient (whose melanoma showed to bear the BRAF V600E mutation in blood, but not at tissue level) our analysis showed that blood samples with PCR evidence for CMC were heterogeneous for BRAF status under limiting-dilution conditions, suggestive of heterogeneity of CMC.Conclusion
The method reported here represents a rapid approach for determination of BRAF status in the blood of patients with CMC. 相似文献8.
Jenn-Yu WuShang-Gin Wu Chih-Hsin YangYih-Leong Chang Yeun-Chung ChangYa-Chieh Hsu Jin-Yuan Shih Pan-Chyr Yang 《Lung cancer (Amsterdam, Netherlands)》2011,72(2):205-212
Introduction
Erlotinib and gefitinib are tyrosine kinase (TK) inhibitors of epidermal growth factor receptor (EGFR) that are effective in treating non-small cell lung cancer (NSCLC). This study aimed to compare their clinical uses and the influence of EGFR mutation.Methods
The usages of erlotinib and gefitinib in advanced NSCLC were analyzed. Clinical data and EGFR mutational status of tumors were collected.Results
Seven hundred and sixteen (716) patients received gefitinib (n = 440) or erlotinib (n = 276) for stage IIIb or IV NSCLC. Erlotinib was prescribed more frequently than gefitinib in males (58.2% vs. 41.8%, p < 0.001), smokers (60.5% vs. 39.5%, p < 0.001), and non-adenocarcinoma (70.6% vs. 29.4%, p < 0.001). Of the 716 study patients, 327 underwent testing for EGFR mutations (170 with mutant EGFR and 157 with wild-type EGFR). Adenocarcinoma in patients with mutant EGFR and non-smoker status in patients with wild-type EGFR were associated with better overall survival after TK inhibitor treatment. In both patient groups with mutant EGFR or wild-type EGFR, the effectiveness of gefitinib and erlotinib, including drug response or overall survival, were not different.Conclusions
Our study revealed the obvious disparity in drug selection between erlotinib and gefitinib in clinical practice. Type of TK inhibitors did not influence treatment outcomes in patients with EGFR mutation or wild-type EGFR. 相似文献9.
Kawahara A Azuma K Sumi A Taira T Nakashima K Aikawa E Abe H Yamaguchi T Takamori S Akiba J Kage M 《Lung cancer (Amsterdam, Netherlands)》2011,74(1):35-40
Background
Recently, we have reported that EGFR mutation-specific antibodies performed well in immunohistochemical analysis, with good sensitivity. We investigated whether this method could detect non-small-cell lung cancer (NSCLC) carrying EGFR mutations in malignant effusions and cerebrospinal fluid (CSF), comparable to the peptide nucleic acid–locked nucleic acid (PNA–LNA) PCR clamp assay. Furthermore, we compared activating EGFR mutations between primary and recurrent NSCLC.Patients and methods
Twenty-four patients with NSCLC effusions and CSF were examined by immunocytochemistry using antibodies specific for the E746-A750 deletion mutation in exon 19 and the L858R point mutation in exon 21. The PNA–LNA PCR clamp assay was used to detect the E746-A750 deletion at exon 19, L858R mutation at exon 21, and T790M mutation at exon 20.Results
We were able to identify EGFR mutations in NSCLC effusion and CSF with a sensitivity of 100% (5/5) using the anti-delE746-A750 antibody and 100% (8/8) using the anti-L858R antibody. Furthermore, in samples without these EGFR mutations, immunocytochemistry with the two specific antibodies identified 91% (10/11) as negative for both the deletion and the point mutations in EGFR. Activating EGFR mutations decreased in recurrent NSCLC compared with primary NSCLC, and the T790M mutation was detected in recurrent NSCLC of patients receiving gefitinib treatment.Conclusions
Identification of EGFR mutations is important for patients with primary and recurrent NSCLC. Rapid and sensitive immunocytochemistry using mutation-specific antibodies to detect EGFR mutations will be useful for diagnosing responsiveness to EGFR-targeted drugs. 相似文献10.
Lin J Goto Y Murata H Sakaizawa K Uchiyama A Saida T Takata M 《British journal of cancer》2011,104(3):464-468
Background:
Oncogenic BRAF mutation had been considered to be a founder event in the formation of melanocytic tumours; however, we recently argued against this notion by showing marked polyclonality of BRAF mutations in acquired melanocytic nevi (Lin et al, J Natl Cancer Inst., 2009; 101:1423–7). Here, we tested whether similar heterogeneity of BRAF mutations exists in primary melanomas.Methods:
We isolated and sequenced single melanoma cells from five primary melanoma tissues using antibodies against human high-molecular-weight melanoma-associated antigen. We also examined 10 primary melanomas by the sensitive Mutector assay detecting the BRAFV600E mutation, as well as by cloning and sequencing of separated alleles. Furthermore, we estimated the frequency of BRAF mutant alleles in paired samples of primary tumour and recurrence or metastasis in three patients.Results:
Single-cell mutation analyses revealed that four of five primary melanomas contained both BRAF-wild-type and BRAF-mutant tumour cells. Tumour heterogeneity in terms of BRAF mutations was also shown in 8 of 10 primary melanomas. Selection of BRAF mutant alleles during progression was demonstrated in all the three patients.Conclusion:
Acquisition of a BRAF mutation is not a founder event, but may be one of the multiple clonal events in melanoma development, which is selected for during the progression. 相似文献11.
Kozu Y Tsuta K Kohno T Sekine I Yoshida A Watanabe S Tamura T Yokota J Suzuki K Asamura H Furuta K Tsuda H 《Lung cancer (Amsterdam, Netherlands)》2011,73(1):45-50
Introduction
Among the mutations of epidermal growth factor receptor (EGFR), deletions in exon 19 (DEL), and point mutations in exon 21 (L858R) predict the response to EGFR-tyrosine kinase inhibitors (TKIs) in primary lung adenocarcinoma. The ability to detecting such mutations using immunohistochemistry (IHC) would be advantageous.Methods
The molecular-based and IHC-based EGFR mutations were analyzed in 577 lung adenocarcinomas using high resolution melting analysis (HRMA) and 2 mutation-specific antibodies, respectively.Results
In the molecular-based analyses, DEL was detected in 135 cases (23%), and L858R was detected in 172 cases (30%). In the IHC-based analyses, a positive reaction was detected in 59 cases (10%) for the DEL-specific antibody, and in 139 cases (24%) for the L858R-specific antibody. With the molecular-based results set as the gold standard, the sensitivity and specificity of the DEL-specific antibody were 42.2% and 99.5%, respectively, while the sensitivity and specificity of the L858R-specific antibody were 75.6% and 97.8%, respectively. The antibody specificities improved when the threshold for the mutation-positive reactions was set as >50% of immunopositive tumor cells. The significant predictors of the clinical response to EGFR-TKI were molecular-based EGFR mutations (p < 0.001) and IHC-based EGFR mutations (p = 0.001). However, a multivariate analysis revealed that only molecular-based EGFR mutations were significantly correlated with the clinical response (p < 0.001).Conclusions
Mutation-specific antibodies demonstrated extremely high specificities, but their sensitivities were not higher than those of molecular-based analyses. However, IHC should be performed before a molecular-based analysis, because it is more cost-effective and can effectively select candidates for EGFR-TKI therapy. 相似文献12.
Bando H Yoshino T Tsuchihara K Ogasawara N Fuse N Kojima T Tahara M Kojima M Kaneko K Doi T Ochiai A Esumi H Ohtsu A 《British journal of cancer》2011,105(3):403-406
Background:
We aimed to compare the sensitive and quality-controlled KRAS testing with direct sequencing and to assess the impact on decision making of treatment.Patients and methods:
We analysed genomic DNA isolated from macrodissected formalin-fixed paraffin-embedded specimens by direct sequencing and an amplification refractory mutation system–Scorpion assay (ARMS/S) method. Cetuximab was administered to patients identified as having wild-type (WT) KRAS using direct sequencing. Therapeutic effects were evaluated according to their KRAS status as determined by ARMS/S.Results:
Among the 159 patients, the overall mutation rate was determined to be 37.0% by direct sequencing and 44.0% by ARMS/S. For the patients diagnosed as WT by direct sequencing and treated with cetuximab (n=47), a response rate of 16.0% was observed for 38 ARMS/S WT patients, whereas 9 ARMS/S mutant (MUT) patients failed to respond. The ARMS/S WT patients showed significant improvement in progression-free survival (PFS) and overall survival (OS) compared with ARMS/S MUT patients (PFS median 5.0 vs 1.7 months, hazards ratio (HR)=0.29, P=0.001; OS median 12.1 vs 3.8 months, HR=0.26, P=0.001).Conclusion:
Sensitive and quality-controlled KRAS testing may provide improved predictive power to determine the efficacy of anti-epidermal growth factor antibodies. 相似文献13.
Han SA Park SK Ahn SH Lee MH Noh DY Kim LS Noh WC Jung Y Kim KS Kim SW;Korean Breast Cancer Study Group 《Clinical oncology (Royal College of Radiologists (Great Britain))》2011,23(7):434-441
Aims
The primary aims of the Korean Hereditary Breast Cancer (KOHBRA) study are to estimate the prevalence of BRCA1/2 mutations and ovarian cancer among a high-risk group of patients with hereditary breast cancer and their families.Materials and methods
The KOHBRA study is a prospective multicentre cohort identifying cases and their families. Between May 2007 and May 2010, the KOHBRA study enrolled up to 2000 subjects. All participants received genetic counselling and BRCA genetic testing; the clinical information and blood samples for blood banking were collected. An interim analysis of the prevalence of BRCA1/2 mutations and ovarian cancer in Korean subjects was determined from the initial 975 patients who presented to 33 centres.Results
By April 2009, a total of 167 mutation carriers among 853 probands were identified. The prevalence of the BRCA mutation was as follows: 24.8% (106/428) for breast cancer patients with a family history of breast/ovarian cancers; 11.3% (24/212) for patients with early-onset (<35 years) breast cancer without a family history; 22.1% (15/68) for patients with bilateral breast cancer; male breast cancer in 8.3% (1/12); and 33.4% (1/3) for patients with breast and ovarian cancer.Conclusions
The results of this study suggest that the prevalence of BRCA mutations in Korean subjects is similar to the prevalence reported among Western cohorts. However, weak family history and non-familial early-onset of breast cancer were significant factors associated with carrying the BRCA mutation in Korean breast cancer patients. Completion of the KOHBRA study is needed to confirm these findings. 相似文献14.
A. Chakravorty N. SanmugalingamA. Shrestha E. ThomeeJ. Rusby N. RocheF. MacNeill 《European journal of surgical oncology》2011,37(2):122-126
Aims
Axillary nodal status is the most important prognostic indicator which in turn influences adjuvant therapy and long term outcomes. The aim of this study was to compare total nodal yields from primary axillary lymph node dissection (pALND) with completion ALND after a cancer positive SLNB: either concurrently (cALND) following intra-operative assessment (IOA) of the SLN’s or as a delayed procedure (dALND) when the SLN was found to be cancer positive on post-operative histological examination.Methods
All axillary procedures performed between May 2006 and September 2009 were identified from a prospective database and categorised into four groups: SLNB with no further axillary surgery, pALND, cALND and dALND. Total nodal yield was the sum of SLN/s and ALND yields.Results
Of 1025 axillary procedures, ALND accounted for 332 (32.4%) of which 207 (62.3%) underwent pALND, 43 (12.9%) cALND, and 82 (24.6%) dALND. Median nodal yields were 15.0, 16.0 and 14.5 respectively (p = 0.3).Conclusion
Total nodal yields for primary, concurrent and delayed ALND were comparable suggesting completion dALND performed as a second operation does not compromise axillary staging. 相似文献15.
Background
The aim of this study was to explore circulating tumor cell (CTC) detection in advanced non-small cell lung cancer (NSCLC). CTCs may not only serve as a prognostic marker in selected tumor types, but may also be useful as pharmacodynamic marker in drug development.Methods
Fourty-six advanced NSCLC patients and fourty-six healthy controls were included in the study and 8.0 ml of peripheral blood was obtained from each of the participants. Immunomagnetic bead enrichment for cells expressing epithelial cell adhesion molecule (EpCAM) was performed, followed by multi-marker quantitative real-time PCR of a panel of marker genes: cytokeratin 7 (CK7), cytokeratin 19 (CK19), human epithelial glycoprotein (EGP) and fibronectin 1 (FN1). Using quadratic discriminant analysis (QDA), expression values were combined into a single score, which indicated CTC-positivity or -negativity. Test characteristics were assessed using receiver operating characteristic (ROC) curve analysis.Results
ROC curve analysis showed capability of discrimination between advanced NSCLC patients and healthy controls (area = 0.712; 95% CI 0.606-0.819; P < 0.001). A cut-off minimizing overall misclassification for QDA-positivity reached a sensitivity of 46% (95% CI 31-61) and a specificity of 93% (95% CI 82-99).Conclusions
In this exploratory study, an assay was developed for discriminating CTCs in peripheral blood samples of advanced NSCLC patients from healthy controls. The assay demonstrated an acceptable sensitivity in combination with good specificity. Further validation studies should take place in NSCLC patients and a matched control group. 相似文献16.
Nina Turnšek Hitij Izidor Kern Aleksander Sadikov Lea Knez Karmen Stanič Matjaž Zwitter Tanja Cufer 《Clinical lung cancer》2017,18(3):e187-e196
Introduction
The sensitivity and specificity of immunohistochemistry (IHC) was compared with the standard polymerase chain reaction (PCR)-based method for detecting common activating epidermal growth factor receptor (EGFR) mutations in non–small-cell lung cancer (NSCLC). Additionally, we evaluated predictive value of IHC EGFR mutation–positive status for EGFR tyrosine kinase inhibitor (TKI) treatment outcome and estimated cost-effectiveness for the upfront IHC testing.Methods
The trial included 79 consecutive EGFR mutation–positive and 29 EGFR mutation–negative NSCLC cases diagnosed with reflex PCR-based testing. Two mutation-specific antibodies against the most common exon 19 deletion, namely E746-A750del (clone SP111) and L858R mutation (clone SP125) were tested by using automated immunostainer. Sixty of 79 EGFR mutation–positive cases were treated with EGFR TKIs for advanced disease and included in treatment outcome analysis. A decision tree was used for the cost-effectiveness analysis.Results
The overall sensitivity and specificity of the IHC-based method compared with the PCR-based method were 84.8% (95% confidence interval [CI] 74.6–91.6) and 100% (95% CI 85.4–100), respectively. The median progression-free survival (PFS) and overall survival (OS) of patients with IHC-positive EGFR mutation status were highly comparable to the total cohort (PFS: 14.3 vs. 14.0 months; OS: 34.4 vs. 34.4 months). The PCR and IHC cost ratio needs to be approximately 8-to-1 and 4-to-1 in White and Asian populations, respectively, to economically justify upfront use of IHC.Conclusion
The trial confirmed an excellent specificity with fairly good sensitivity of IHC with mutation-specific antibodies for common EGFR mutations and the accuracy of IHC testing for predicting response to EGFR TKIs. The use of upfront IHC depends mainly on the population EGFR mutation positivity probability. 相似文献17.
Ren S Zhou S Wu F Zhang L Li X Zhang J Xu J Lv M Zhang J Zhou C 《Lung cancer (Amsterdam, Netherlands)》2012,75(1):102-109
Background
Single nucleotide polymorphism (SNP) in DNA repair genes can be used to explain the differences in survival of platinum-treated non-small cell lung cancer (NSCLC) patients regardless of their performance status. To define the role of DNA repair gene SNPs in NSCLC patients, we investigated the association between survival and 12 different SNPs of 9 DNA repair genes.Methods
340 patients were treated with platinum-based chemotherapy. Polymorphisms were detected by real time PCR with TaqMan probe, using genomic DNA extracted from peripheral blood samples. Multivariate logistic or Cox regression analyses were used to adjust for possible confounding variables.Results
The median overall survival time was 15 months and it was significantly longer in patients harboring ERCC1 118 C/T or T/T allele: 18 months as compared to 13.8 months for the C/C allele (P = 0.014). Subgroup analysis revealed that ERCC1 118 C/T or T/T was associated with increased survival in elderly patients (P = 0.018), male (P = 0.022), squamous carcinoma (P = 0.003), smoker (P = 0.076) and those treated with non-gemcitabine/cisplatin or carboplatin (non-GP/GC) regimen (P = 0.023). XRCC3C/C was associated with better survival in non-gemcitabine/cisplatin treated patients (P = 0.014). Both of CCNH-V270A C/C or C/T and XPD 751 A/A showed a significant longer survival in the squamous cell carcinoma subgroup (P = 0.047 and P = 0.034 respectively).Conclusion
Present data indicates that ERCC1 118 C/T or T/T might provide a better prognostic predictive marker of NSCLC patients treated with platinum-based chemotherapy, mainly in elderly subgroup, male, squamous carcinoma, smoker and those treated with non-GP/GC regimen. 相似文献18.
Hye-Ryoun Kim Sung Yong Lee Dae-Sung Hyun Min Ki Lee Hyun-Kyung Lee Chang-Min Choi Sei-Hoon Yang Young-Chul Kim Yong Chul Lee Sun Young Kim Seung Hun Jang Jae Cheol Lee Kye Young Lee 《Journal of experimental & clinical cancer research : CR》2013,32(1):50
Background
Epidermal growth factor receptor (EGFR)-activating mutations are major determinants in predicting the tumor response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). Noninvasive test for the detection of EGFR mutations is required, especially in NSCLC patients from whom tissue is not available. In this study, we assessed the feasibility of detection of EGFR mutations in free DNA circulating in plasma.Methods
Plasma samples of 60 patients with partial response to gefitinib were analyzed to detect EGFR-activating mutations in exons 19 and 21. Forty (66.7%) of patients had tumor EGFR mutation results. EGFR mutations in plasma were detected using the peptide nucleic acid (PNA)-mediated polymerase chain reaction (PCR) clamping method. All clinical data and plasma samples were obtained from 11 centers of the Korean Molecular Lung Cancer Group (KMLCG).Results
Of the 60 patients, 39 were female and the median age was 62.5 years. Forty-three patients never smoked, 53 had adenocarcinomas, and seven had other histologic types. EGFR-activating mutation was detected in plasma of 10 cases (exon 19 deletion in seven and exon 21 L858R point mutation in three). It could not be found in plasma after treatment for 2 months. When only patients with confirmed EGFR mutation in tumor were analyzed, 17% (6 of 35) of them showed positive plasma EGFR mutation and the mutation type was completely matched with that in tumor. There was no statistically significant difference in clinical parameters between patients with EGFR mutations in plasma and those without EGFR mutations.Conclusions
The detection rate of EGFR mutations from plasma was not so high despite highly sensitive EGFR mutation test suggesting that more advances in detection methods and further exploration of characteristics of circulating free DNA are required. 相似文献19.
Lin Li Zijin Zhang Zhixin Bie Zheng Wang Ping Zhang Xin Nie Yuanming Li Hui Wang Bin Ai Gang Cheng 《中国癌症研究》2015,27(3):294-300