Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “EGFR mutation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources
PubMed2006

Mutation of epidermal growth factor receptor gene in adenosquamous carcinoma of the lung.

We have investigated 26 adenosquamous lung cancer tissues and found that four EGFR mutations were mainly in female and non-smoker lung cancer. However, EGFR mutation at kinase domain was exclusive with K-ras mutation. However, smoking and gender status could affect the occurrence of EGFR mutation. There was no difference in EGFR mutation status if analysis was performed in never smoker female subgroup.

Aged↗
PubMed2006

Expression profile-defined classification of lung adenocarcinoma shows close relationship with underlying major genetic changes and clinicopathologic behaviors.

PURPOSE: This study was conducted to gain insight into the relationship between expression profiles and underlying genetic changes, which are known to be important for the pathogenesis of lung cancers. METHODS: Expression profiles of 18,175 unique genes and three major targets for genetic changes, p53, epidermal growth factor receptor (EGFR), and K-ras, were investigated in 149 patients with non-small-cell lung cancer, including 90 patients with adenocarcinoma to determine their relationships with various clinicopathologic features and Gene Ontology (GO) terms. RESULTS: This study successfully established a basis for expression profile-defined classification, which can classify adenocarcinomas into two major types, terminal respiratory unit (TRU) type and non-TRU type. Our GO term-based identifier of particular biologic processes, molecular functions, and cellular compartments clearly showed characteristic retention of normal peripheral lung features in TRU type, in sharp contrast to the significant association of non-TRU type with cell cycling and proliferation-related features. While significantly higher frequency of EGFR mutation was observed in TRU type, we found that the presence of EGFR mutations was a significant predictor of shorter postoperative survival for TRU type, independent of disease stage. We were also able to identify a set of genes in vivo with significant upregulation in the presence of EGFR mutations. CONCLUSION: This study has shed light on heterogeneity in lung cancers, especially in adenocarcinomas, by establishing a molecularly, genetically, and clinically relevant, expression profile-defined classification. Future studies using independent patient cohorts are warranted to confirm the prognostic significance of EGFR mutations in TRU-type adenocarcinoma.

Adenocarcinoma↗
PubMed2006

Clinical course of patients with non-small cell lung cancer and epidermal growth factor receptor exon 19 and exon 21 mutations treated with gefitinib or erlotinib.

PURPOSE: In patients with non-small cell lung cancer (NSCLC), mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain have been associated with sensitivity to erlotinib and gefitinib. We undertook this study to explore the relationship between EGFR mutation type and clinical variables, including treatment with gefitinib and erlotinib. EXPERIMENTAL DESIGN: In patients with NSCLC, EGFR exon 19 deletion mutations and EGFR L858R point mutations were analyzed by nonsequencing PCR-based methods from paraffin blocks of tissue obtained before treatment. The results were correlated with clinical information (sex, pathologic subtype, race/ethnicity, treatment, and overall survival). RESULTS: The two most common EGFR mutations were identified in 24% (70 of 291; 95% confidence interval, 26%-38%) of tumors from patients with NSCLC. EGFR mutation was associated with Asian ethnicity (P = 0.0023) and being a "never smoker" (P = 0.0001). Among patients with EGFR mutations, 39% (27 of 70) had EGFR L858R, whereas 61% (43 of 70) had an EGFR exon 19 deletion. After treatment with erlotinib (n = 12) or gefitinib (n = 22), patients with EGFR mutations had a median overall survival of 20 months. After treatment with erlotinib or gefitinib, patients with EGFR exon 19 deletions had significantly longer median survival than patients with EGFR L858R (34 versus 8 months; log-rank P = 0.01). CONCLUSIONS: EGFR mutations in exons 19 or 21 are correlated with clinical factors predictive of response to gefitinib and erlotinib. Those with EGFR exon 19 deletion mutations had a longer median survival than patients with EGFR L858R point mutation. These observations warrant confirmation in a prospective study and exploration of the biological mechanisms of the differences between the two major EGFR mutations.

Adult↗
PubMed2005

Aberrant methylation: common in thymic carcinomas, rare in thymomas.

Thymic carcinoma, which is a rare epithelial neoplasm of the thymus gland, is different from thymoma in its clinical and pathological features. To clarify the mechanism underlying the aggressive behavior of thymic carcinoma, we examined the clinicopathologic features, aberrant methylation patterns of the tumor suppressor genes, and epidermal growth factor receptor (EGFRs) mutation in both thymic carcinomas and thymomas. Clinical data of 11 thymic cancers and 13 thymomas were reviewed. Resected samples of 5 thymic cancers and 6 thymomas selected from 24 cases were used for methylation and mutation studies. Positive tumor markers were more frequent in thymic cancers than in thymomas (p=0.0233), and the methylation index, which reflects the overall methylation pattern, was significantly higher in thymic carcinomas (p=0.0053). No tumors showed a mutation of EGFR, KRAS, and HER2. Thymic carcinoma is distinct from thymoma not only with respect to clinicopathological features, but also aberrant methylation patterns of the tumor suppressor genes.

Adult↗
PubMed2005

Epithelial versus mesenchymal phenotype determines in vitro sensitivity and predicts clinical activity of erlotinib in lung cancer patients.

Significant improvements in the outcome of non-small cell lung carcinoma (NSCLC) have been reported in patients treated with the epidermal growth factor receptor (EGFR) inhibitor, erlotinib. To discover biomarkers for the enrichment of patients who might benefit from treatment, a pharmacogenomic approach was used to identify gene signatures that may predict erlotinib activity using in vitro model systems. Erlotinib sensitivity in a panel of 42 NSCLC cell lines was determined by EGFR-mediated proliferative potential, EGFR mutations, and/or EGFR gene amplification, thus supporting an underlying biological mechanism of receptor activation. A strong multigene signature indicative of an epithelial to mesenchymal transition (EMT) was identified as a determinant of insensitivity to erlotinib through both supervised and unsupervised gene expression approaches. This observation was further supported by expression analysis of classic EMT marker proteins, including E-cadherin and vimentin. To investigate the clinical relevance of these findings, we examined expression of the epithelial marker E-cadherin by immunohistochemistry on primary tumor samples from subjects enrolled in a randomized NSCLC clinical trial in which erlotinib in combination with chemotherapy previously failed to show clinical activity. The majority (75%) of the 87 subjects tested showed strong E-cadherin staining and exhibited a significantly longer time to progression (hazard ratio, 0.37; log rank P=0.0028) and a nonsignificant trend toward longer survival with erlotinib plus chemotherapy treatment versus chemotherapy alone. These data support a potential role for EMT as a determinant of EGFR activity in NSCLC tumor cells and E-cadherin expression as a novel biomarker predicting clinical activity of the EGFR inhibitor erlotinib in NSCLC patients.

Antineoplastic Agents↗
PubMed2005

Epidermal growth factor receptor gene mutations and increased copy numbers predict gefitinib sensitivity in patients with recurrent non-small-cell lung cancer.

PURPOSE: To evaluate epidermal growth factor receptor (EGFR) mutations and copy number as predictors of clinical outcome in patients with non-small-cell lung cancer (NSCLC) receiving gefitinib. PATIENTS AND METHODS: Sixty-six patients with NSCLC who experienced relapse after surgery and received gefitinib were included. Direct sequencing of exons 18 to 24 of EGFR and exons 18 to 24 of ERBB2 was performed using DNA extracted from surgical specimens. Pyrosequencing and quantitative real-time polymerase chain reaction were performed to analyze the allelic pattern and copy number of EGFR. RESULTS: Thirty-nine patients (59%) had EGFR mutations; 20 patients had deletional mutations in exon 19, 17 patients had missense mutations (L858R) in exon 21, and two patients had missense mutations (G719S or G719C) in exon 18. No mutations were identified in ERBB2. Response rate (82% [32 of 39 patients] v 11% [three of 27 patients]; P < .0001), time to progression (TTP; median, 12.6 v 1.7 months; P < .0001), and overall survival (median, 20.4 v 6.9 months; P = .0001) were significantly better in patients with EGFR mutations than in patients with wild-type EGFR. Increased EGFR copy numbers (> or = 3/cell) were observed in 29 patients (44%) and were significantly associated with a higher response rate (72% [21 of 29 patients] v 38% [14 of 37 patients]; P = .005) and a longer TTP (median, 9.4 v 2.6 months; P = .038). High EGFR copy numbers (> or = 6/cell) were caused by selective amplification of mutant alleles. CONCLUSION: EGFR mutations and increased copy numbers were significantly associated with better clinical outcome in gefitinib-treated NSCLC patients.

Adult↗
PubMed2006

Detection of EGFR gene mutation in lung cancer by mutant-enriched polymerase chain reaction assay.

PURPOSE: Mutations in the epidermal growth factor receptor (EGFR) gene have been reported to be present in non-small cell lung cancer (NSCLC) and related to the responsiveness of tumors to EGFR tyrosine kinase inhibitors, suggesting its usefulness as a biomarker. Because clinical samples contain tumor and normal cells or genes, a highly sensitive assay for detecting mutation is critical for clinical applications. EXPERIMENTAL DESIGN: The mutant-enriched PCR is a rapid and sensitive assay with selective restriction enzyme digestion. We developed the mutant-enriched PCR assay targeting exons 19 and 21 of EGFR and applied the developed assay to detect mutations in 108 cases of surgically resected specimens of NSCLCs, 18 samples of computed tomography (CT)-guided needle lung biopsies, and 20 samples of pleural fluid. In addition, results were then compared with those from direct sequencing and a nonenriched PCR assay. RESULTS: The mutant-enriched PCR that was proved to enrich one mutant of 2 x 10(3) normal genes detected mutations in 37 cases of 108 resected tumors, seven samples of CT-guided lung biopsies, and seven samples of pleural fluid. Among mutant cases, four resected tumors, two CT-guided lung biopsies, and two pleural fluid were identified as additional mutant cases by the mutant-enriched PCR, which were considered normal based on nonenriched assays. CONCLUSIONS: Our results indicate that EGFR mutations are readily detectable by mutant-enriched PCR in various clinical samples. Thus, mutant-enriched PCR may provide a valuable method of potentially detecting a small fraction of mutant genes in heterogeneous specimens, indicating its possible use in clinical application for NSCLC.

Biopsy↗
PubMed2005

Mutational analysis of EGFR and K-RAS genes in lung adenocarcinomas.

Both epidermal growth factor receptor (EGFR) and RAS gene mutations contribute to the development of non-small cell lung cancer (NSCLC). Because RAS is one of the downstream molecules in the EGFR signal transduction, the association between the somatic mutations of EGFR and RAS may be important in the pathogenesis of NSCLC . However, to date, such data are lacking. In this study, we analyzed the hotspot regions of K-RAS gene (codons 12, 13, 59 and 61) and EGFR gene (exons 18, 19 and 21) in 153 NSCLC tissue samples including 69 adenocarcinomas. Overall, we detected 30 EGFR mutations (19.6%) and 6 K-RAS mutations (3.9%) in the 153 NSCLCs. In the 69 adenocarcinomas, 26 EGFR mutations (37.7%) and six K-RAS mutations (8.7%) were detected. Of note, the 26 tumors with EGFR mutations did not harbor any K-RAS mutations, and the six tumors with K-RAS mutations did not harbor any EGFR mutations. Inverse relationship between K-RAS and EGFR mutations in the lung adenocarcinoma was statistically significant (P=0.046, chi2 test). As regards smoking history, EGFR mutation was significantly associated with never-smoking history, whereas K-RAS mutation was significantly associated with smoking history. Our data suggest that mutations of EGFR and K-RAS genes might separately, but not cooperatively, contribute to lung adenocarcinoma pathogenesis, and that EGFR and K-RAS mutants could separately be anti-neoplastic targets in lung adenocarcinomas.

Adenocarcinoma↗
PubMed2005

Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib.

PURPOSE: Epidermal growth factor receptor (EGFR) mutations have been associated with tumor response to treatment with single-agent EGFR inhibitors in patients with relapsed non-small-cell lung cancer (NSCLC). The implications of EGFR mutations in patients treated with EGFR inhibitors plus first-line chemotherapy are unknown. KRAS is frequently activated in NSCLC. The relationship of KRAS mutations to outcome after EGFR inhibitor treatment has not been described. PATIENTS AND METHODS: Previously untreated patients with advanced NSCLC in the phase III TRIBUTE study who were randomly assigned to carboplatin and paclitaxel with erlotinib or placebo were assessed for survival, response, and time to progression (TTP). EGFR exons 18 through 21 and KRAS exon 2 were sequenced in tumors from 274 patients. Outcomes were correlated with EGFR and KRAS mutations in retrospective subset analyses. RESULTS: EGFR mutations were detected in 13% of tumors and were associated with longer survival, irrespective of treatment (P < .001). Among erlotinib-treated patients, EGFR mutations were associated with improved response rate (P < .05) and there was a trend toward an erlotinib benefit on TTP (P = .092), but not improved survival (P = .96). KRAS mutations (21% of tumors) were associated with significantly decreased TTP and survival in erlotinib plus chemotherapy-treated patients. CONCLUSION: EGFR mutations may be a positive prognostic factor for survival in advanced NSCLC patients treated with chemotherapy with or without erlotinib, and may predict greater likelihood of response. Patients with KRAS-mutant NSCLC showed poorer clinical outcomes when treated with erlotinib and chemotherapy. Further studies are needed to confirm the findings of this retrospective subset analysis.

Adult↗
PubMed2006

Dasatinib (BMS-354825) selectively induces apoptosis in lung cancer cells dependent on epidermal growth factor receptor signaling for survival.

Mutations of the epidermal growth factor receptor (EGFR) selectively activate Akt and signal transducer and activator of transcription (STAT) pathways that are important in lung cancer cell survival. Src family kinases can cooperate with receptor tyrosine kinases to signal through downstream molecules, such as phosphatidylinositol 3-kinase/PTEN/Akt and STATs. Based on the importance of EGFR signaling in lung cancer, the known cooperation between EGFR and Src proteins, and evidence of elevated Src activity in human lung cancers, we evaluated the effectiveness of a novel orally bioavailable Src inhibitor dasatinib (BMS-324825) in lung cancer cell lines with defined EGFR status. Here, we show that cell fate (death versus growth arrest) in lung cancer cells exposed to dasatinib is dependent on EGFR status. In cells with EGFR mutation that are dependent on EGFR for survival, dasatinib reduces cell viability through the induction of apoptosis while having minimal apoptotic effect on cell lines with wild-type (WT) EGFR. The induction of apoptosis in these EGFR-mutant cell lines corresponds to down-regulation of activated Akt and STAT3 survival proteins. In cell lines with WT or resistant EGFR mutation that are not sensitive to EGFR inhibition, dasatinib induces a G(1) cell cycle arrest with associated changes in cyclin D and p27 proteins, inhibits activated FAK, and prevents tumor cell invasion. Our results show that dasatinib could be effective therapy for patients with lung cancers through disruption of cell growth, survival, and tumor invasion. Our results suggest EGFR status is important in deciding cell fate in response to dasatinib.

Apoptosis↗
PubMed2006

Epidermal growth factor receptor activation: how exon 19 and 21 mutations changed our understanding of the pathway.

The discovery of epidermal growth factor receptor (EGFR) mutations in never-smokers has been the most relevant finding ever in non-small cell lung cancer. When patients whose tumors bear the sensitizing mutations are treated with the tyrosine kinase inhibitors gefitinib or erlotinib, we witness response rates and durations never before reported, including complete responses. At the same time, the presence of EGFR mutations has raised numerous new questions, tantalizing data, and new challenges for treatment. This is particularly true as we try to generalize the findings in lung cancer to other malignancies. The indiscriminate use of gefitinib or erlotinib in the general lung cancer population results in meager survival benefit for patients. Similarly, the tyrosine kinase inhibitors have limited activity in a variety of tumor types with EGFR overexpression. This has led to the question of whether EGFR remains a viable target in patients other than those whose tumors contain mutations, and whether the modest activity of cetuximab in colorectal cancer and head and neck cancer represents all that we can expect from inhibition of this pathway in the absence of mutation. Mechanisms of pathway activation other than mutation have been discovered in recent years, and include overexpression mediated by gene amplification or by amplification of a dinucleotide repeat in the EGFR promoter, mutation of an extracellular region on EGFR generating a mutant protein termed EGFRvIII, and enhanced signaling due to heterodimerization with other members of the EGFR family, particularly overexpression of HER2/HER3. The extent to which these paths to EGFR activation will confer sensitivity to the tyrosine kinase inhibitors or to EGFR monoclonal antibodies is being explored. Thus far, published clinical data suggest that there is little room for the administration of gefitinib or erlotinib in the absence of EGFR mutations. The five articles in this edition of CCR Focus will address the various mechanisms of EGFR pathway activation and provide insight into the potential for translation into clinical relevance.

Antibodies, Monoclonal↗
PubMed2006

Epidermal growth factor receptor mutations and response to chemotherapy in patients with non-small-cell lung cancer.

BACKGROUND: The association of epidermal growth factor receptor (EGFR) mutations with the response to conventional cytotoxic chemotherapeutic agents in non-small-cell lung cancer patients has not been investigated. We retrospectively analyzed the associations between response to chemotherapy and molecular markers associated with gefitinib responsiveness including EGFR mutations. METHODS: EGFR (exons 18, 19 and 21) and K-ras mutations (exon 2) were studied by direct sequencing and p-Erk and p-Akt expressions were studied by immunohistochemistry in archival paraffin embedded tissues. Response rate (RR) and time-to-progression (TTP) of prior chemotherapy by platinum, paclitaxel and gemcitabine were analyzed with respect to the presence of EGFR and K-ras mutations, and p-Erk and p-Akt expressions. RESULTS: Of 90 patients investigated, 75 received platinums and 45 received paclitaxel as first-line chemotherapy agents. The RRS and TTPS of platinum- and paclitaxel-containing regimens were not affected by EGFR or K-ras mutations, nor by p-Erk or p-Akt expression. Fifty-seven patients received gemcitabine as first- or second-line chemotherapy. RR was not affected by EGFR or K-ras mutations or by p-Akt expression. However, all responders to gemcitabine exhibited (+) p-Erk expression [RR 30.6% for p-Erk (+) versus 0% for p-Erk (-), P = 0.01]. TTP was not affected by EGFR or K-ras mutations or by p-Erk or p-Akt expression. CONCLUSIONS: EGFR mutations did not affect response to conventional chemotherapeutic agents, namely platinums, paclitaxel and gemcitabine. Our results also suggest that it may be undesirable to use gemcitabine in patients with tumors not expressing p-Erk.

Antineoplastic Agents↗
PubMed2006

Use of cigarette-smoking history to estimate the likelihood of mutations in epidermal growth factor receptor gene exons 19 and 21 in lung adenocarcinomas.

PURPOSE: Lung adenocarcinomas with mutations in exons 19 and 21 of the epidermal growth factor receptor gene (EGFR) demonstrate sensitivity to gefitinib or erlotinib. Investigators have reported an association between EGFR mutations and the amount and duration of cigarette smoking, with the highest incidence of mutations seen in never smokers. METHODS: EGFR exon 19 and 21 mutation status was determined in 265 tumor samples using direct sequencing, polymerase chain reaction (PCR), or PCR-based restriction fragment length polymorphism analysis. A detailed smoking history was obtained. Patients were categorized as never smokers (< 100 lifetime cigarettes), former smokers (quit > or = 1 year ago), or current smokers (quit < 1 year ago). RESULTS: We detected EGFR mutations in 34 (51%) of 67 never smokers (95% CI, 38% to 64%), 29 (19%) of 151 former smokers (95% CI, 13% to 27%), and two (4%) of 47 current smokers (95% CI, 1% to 16%). Significantly fewer EGFR mutations were found in people who smoked for more than 15 pack-years (P < .001) or stopped smoking less than 25 years ago (P < .02) compared with individuals who never smoked. The number of smoking pack-years and smoke-free years predicted the prevalence of EGFR mutations (areas under receiver operating characteristic curve = 0.78 and 0.77, respectively). CONCLUSION: The likelihood of EGFR mutations in exons 19 and 21 decreases as the number of pack-years increases. Mutations were less common in people who smoked for more than 15 pack-years or who stopped smoking cigarettes less than 25 years ago. These data can assist clinicians in assessing the likelihood of exon 19 and 21 EGFR mutations in patients with lung adenocarcinoma when mutational analysis is not feasible.

Adenocarcinoma↗
PubMed2026

Machine Learning-Based Preoperative Predicting TERT Promoter Mutation and EGFR Gene Amplification Phenotype in IDH Wild-Type Glioblastoma Using Advanced MR Habitat Imaging.

BACKGROUND AND PURPOSE: The telomerase reverse transcriptase (TERT) gene promoter mutation is a crucial factor for identifying an isocitrate dehydrogenase (IDH) wild-type glioblastoma with poor prognosis, and the epidermal growth factor receptor (EGFR) amplification may be a potential prognostic factor. The purpose of this study was to investigate the value of the tumor habitats imaging model on advanced MRI in predicting TERT promoter mutation and EGFR gene amplification phenotype of IDH wild-type glioblastoma. MATERIALS AND METHODS: One hundred seventy-nine patients with pretreatment conventional MRI, DWI, and DSC-PWI were included. The data were divided into the training set (n=112), test set (n=29), and time-independent validation set (n=38). Based on the ADC and CBV map, the solid tumor area was split into several habitat subregions using the k-means clustering algorithm (hypovascular hypercellular area, hypervascular area, and hypovascular hypocellular area). In the training set, TERT promoter mutation and EGFR gene amplification phenotype prediction models were constructed using the random forest method. The reliability of prediction models was validated in the test and the time-independent validation sets. Receiver operating characteristic (ROC) curve analysis, calibration curve, and decision curve analysis (DCA) were used. RESULTS: The area under the curve (AUC) of the training, test, and validation sets of the TERT promoter prediction model was 0.877, 0.783, and 0.796, respectively. The accuracy of the TERT promoter prediction model was 82.1%, 75.9%, and 76.3%, respectively. The AUCs of the 3 sets for the EGFR gene amplification status prediction model were 0.877, 0.784, and 0.878, respectively. The accuracy of the EGFR gene amplification status prediction model was 79.5%, 75.9%, and 89.5%, respectively. Moreover, the prediction probability of these models was in good agreement with the actual result. CONCLUSIONS: The tumor habitat imaging model based on advanced MRI was useful for accurately predicting TERT promoter mutation and EGFR amplification status in IDH wild-type glioblastoma.

Humans↗
PubMed2005

EGFR overexpression in malignant pleural mesothelioma. An immunohistochemical and molecular study with clinico-pathological correlations.

The epidermal growth factor receptor (EGFR) is overexpressed in many epithelial malignancies, against which some antitumoral drugs have been developed. There is a lack of information as to EGFR expression in malignant pleural mesothelioma (MPM), an aggressive and fatal cancer poorly responsive to current oncological treatments. Our aim was to: (a) compare EGFR immunohistochemical expression with mRNA levels measured by real time PCR; (b) assess the relationships between EGFR expression and clinico-pathological data including survival; (c) analyze the EGFR mutations. We developed an immunohistochemical method of EGFR evaluation based on the number of immunoreactive cells and staining intensity in 61 MPMs. EGFR immunoreactivity was documented in 34/61 (55.7%) cases. A significant correlation between EGFR protein and mRNA levels (p = 0.0077) was found, demonstrating the reliability of our quantification method of EGFR membrane expression. Radically resected patients (p = 0.005) and those with epithelial histotype (p = 0.048) showed an increased survival. No statistical correlation between EGFR immunoreactivity and patients survival was observed. No EGFR mutation was documented. This study documents EGFR overexpression in MPM at the protein and the transcriptional levels; it proposes a reliable method for EGFR expression evaluation in MPM. EGFR levels are not associated with clinico-pathological features of patients, including survival.

Adult↗
PubMed2004

High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan.

PURPOSE: Epidermal growth factor receptor (EGFR) mutations related to gefitinib responsiveness in non-small cell lung cancer have been found recently. Detection of EGFR mutations has become an important issue for therapeutic decision-making in non-small cell lung cancer. EXPERIMENTAL DESIGN: Mutational analysis of the kinase domain of EGFR coding sequence was done on 101 fresh frozen tumor tissues from patients without prior gefitinib treatment and 16 paraffin-embedded tumor tissues from patients treated with gefitinib. Detection of phosphorylated EGFR by immunoblot was also done on frozen tumor tissues. RESULTS: The 101 non-small cell lung cancer tumor specimens include 69 adenocarcinomas, 24 squamous cell carcinomas, and 8 other types of non-small cell lung cancers. Mutation(s) in the kinase domain (exon 18 to exon 21) of the EGFR gene were identified in 39 patients. All of the mutations occurred in adenocarcinoma, except one that was in an adenosquamous carcinoma. The mutation rate in adenocarcinoma was 55% (38 of 69). For the 16 patients treated with gefitinib, 7 of the 9 responders had EGFR mutations, and only 1 of the 7 nonresponders had mutations, which included a nonsense mutation. The mutations seem to be complex in that altogether 23 different mutations were observed, and 9 tumors carried 2 mutations. CONCLUSIONS: Data from our study would predict a higher gefitinib response rate in lung adenocarcinoma patients in Chinese and, possibly, other East Asian populations. The tight association with adenocarcinoma and the high frequency of mutations raise the possibility that EGFR mutations play an important role in the tumorigenesis of adenocarcinoma of lung, especially in East Asians.

Adenocarcinoma↗
PubMedDate not supplied

Diffuse micronodular pulmonary metastasis of lung adenocarcinoma predicts gefitinib response in association with epidermal growth factor receptor mutations.

Female, non-smoker, Asian ethnicity and adenocarcinoma histology are the major clinical predictors of gefitinib response in non-small cell lung cancer, as shown in previous studies. Recently, response to gefitinib has been associated with epidermal growth factor receptor (EGFR) mutations. Higher rates of mutation were seen in females, patients with adenocarcinomas, the Asian population and never-smokers, which may explain the clinical response predictors. The presence of diffuse micronodular pulmonary metastasis on chest imaging as a novel clinical predictor of its response is proposed here. Two cases of lung adenocarcinomas in men presenting with diffuse micronodular pulmonary metastasis were encountered. Both patients showed a major response to gefitinib. The dramatic reduction of micronodular pulmonary nodules throughout both lungs on computed tomography scans was achieved after treatment for a couple of months with 250 mg of oral gefitinib. In the molecular analysis, one patient had a heterozygous delL746-A750 mutation and the other had a heterozygous L858R EGFR mutation. In conclusion, patients with lung adenocarcinoma, even men, who presented with bilateral diffuse micronodular metastatic spread to the lungs tended to have an activated EGFR mutation. Therefore, they are most likely to receive benefits from molecular target drugs such as gefitinib and possibly erlotinib.

Adenocarcinoma↗