Prognostic Significance of Glucose Metabolism as GLUT1 in Patients with Pulmonary Pleomorphic Carcinoma.

Glucose metabolism is necessary for tumor progression, metastasis, and survival in various human cancers. Glucose transporter 1 (GLUT1), in particular, plays an important role in the mechanism of ¹8F-FDG (2-[¹8F]-fluoro-2-deoxy-d-glucose) within tumor cells. However, little is known about the clinicopathological significance of GLUT1 in patients with pulmonary pleomorphic carcinoma (PPC). Adenocarcinoma, squamous cell carcinoma, adenosquamous cell carcinoma, poorly differentiated carcinoma, large cell carcinoma, and others were identified as epithelial components, and spindle-cell type, giant-cell type, and both spindle- and giant-cell types were identified as sarcomatous components. This study was performed to determine the prognostic impact of GLUT1 expression in PPC. Patients with surgically resected PPC (n = 104) were evaluated by immunohistochemistry analysis to detect GLUT1 expression and determine the Ki-67 labeling index using specimens of the resected tumors. GLUT1 was highly expressed in 48% (50/104) of all patients, 42% (20/48) of the patients with an adenocarcinoma component, and 53% (30/56) of the patients with a nonadenocarcinoma component. High expression of GLUT1 was significantly associated with advanced stage, vascular invasion, pleural invasion, and tumor cell proliferation as determined by Ki-67 labeling. GLUT1 expression and tumor cell proliferation were significantly correlated according to the Ki-67 labeling in all patients (Spearman's rank; r = 0.25, p < 0.01). In multivariate analysis, GLUT1 was identified as a significant independent marker for predicting a poor prognosis. GLUT1 is an independent prognostic factor for predicting the poor prognosis of patients with surgically resected PPC.

Clinical Significance of Various Drug-Sensitivity Markers in Patients with Surgically Resected Pulmonary Pleomorphic Carcinoma.

Various drug-sensitivity markers are potentially responsible for tumor progression and chemotherapy resistance in cancer patients with both epithelial and sarcomatous components; however, the clinicopathological significance of drug-sensitivity markers in patients with pulmonary pleomorphic carcinoma (PPC) remains unknown. Here, we clarified the prognostic impact of these drug-sensitivity markers in PPC by performing immunohistochemical and clinicopathologic analyses of samples from 105 patients with surgically resected PPC in order to evaluate levels of vascular endothelial growth factor 2 (VEGFR2), stathmin 1 (STMN1), tubulin ß3 class III (TUBB3), thymidylate synthetase (TS), topoisomerase II (Topo-II), glucose-regulated protein, and 78 kDa (GRP78)/binding immunoglobulin protein (BiP). We observed the rates of high expression for VEGFR2, STMN1, TUBB3, TS, Topo-II, and GRP78/BiP were 33% (39/105), 35% (37/105), 61% (64/105), 51% (53/105), 31% (33/105), and 51% (53/105) of the samples, respectively. Moreover, multivariate analysis identified VEGFR2 and GRP78/BiP as significant independent markers for predicting worse prognosis. These findings suggested elevated VEGFR2 and decreased GRP78/BiP levels as independent factors for predicting poor outcomes following surgical resection in patients with PPC.

Fas/FasL signaling is critical for the survival of exhausted antigen-specific CD8+ T cells during tumor immune response.

Antigen (Ag)-specific activated CD8+ T cells are critical for tumor elimination but become exhausted, and thus, dysfunctional during immune response against the tumor due to chronic antigen stimulation. The signaling of immune checkpoint receptors is known to be a critical component in this exhaustion; however, the fate of these exhausted CD8+ T cells remains unclear. Therefore, to elucidate this, we followed the fate of Ag-specific CD8+ T cells by directly visualizing them using MHC class I tetramers coupled with ovoalubumin257-264 in C57BL/6 mice inoculated with EG.7. We found that the number of generated Ag-specific activated CD8+ T cells decreased via apoptosis during a prolonged tumor immune response. However, the number of Ag-specific CD8+ T cells was significantly higher in Fas ligand (FasL)-dysfunctional gld mice than in control mice, resulting in suppressed tumor growth. In contrast, the enforced expression of Bcl-2 failed to rescue apoptosis of the exhausted CD8+ T cells following EG.7 inoculation. These results suggest that Fas/FasL signaling is critical for the survival of exhausted CD8+ T cells during the tumor immune response.

Video-Assisted Thoracoscopic Surgery after Preoperative CT-Guided Lipiodol Marking of Small or Impalpable Pulmonary Nodules.

PURPOSE: Small pulmonary lesions that include ground-glass attenuation have been increasingly discovered because of progressive imaging diagnostic technologies. Despite the detection of such small lesions, sometimes it is quite difficult to localize them because of their size or considerable depth from the visceral pleura. In the present study, we examined the usefulness of computed tomography-guided lipiodol marking for thoracoscopic resection of impalpable pulmonary nodules. METHODS: Fifty-six patients with an undiagnosed peripheral lesion(s) of the lung who had undergone preoperative computed tomography-guided lipiodol marking followed by video-assisted thoracoscopic surgery were studied. RESULTS: All of the nodules were successfully marked by computed tomography-guided lipiodol marking, and all except for one case were localized by means of intraoperative fluoroscopy as clear spots. With regard to complications, pneumothorax occurred in 21 patients (37.5%), and only one patient required transient drainage. Although hemorrhaging in the lung parenchyma and hemosputum occurred in nine patients (16.1%) and one patient (1.8%), respectively, no patients were in serious condition. No intra- or postoperative mortality or morbidity was observed. CONCLUSION: Preoperative computed tomography-guided lipiodol marking of small or impalpable pulmonary nodules is a safe and useful procedure for thoracoscopic resection of the lung.

Single-incision laparoscopic surgery for a small-intestinal gastrointestinal stromal tumor: report of a case.

Our report concerns a 64-year-old man with a small-intestinal gastrointestinal stromal tumor (GIST), which was successfully treated with single-incision laparoscopic surgery (SILS). Small-bowel endoscopy detected a submucosal tumor located approximately 10 cm from the ligament of Treitz in the wall of the proximal jejunum. Contrast-enhanced computed tomography revealed a tumor (diameter, 4 cm) containing high- and low-density areas in the proximal jejunum. On 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET), the tumor demonstrated intense FDG uptake (maximum standard uptake value, 3.82), whereas it displayed high signal intensity on diffusion-weighted magnetic resonance images. No metastatic lesions were observed. The patient was diagnosed with a jejunal GIST. Wedge resection of the jejunum was performed using the SILS procedure. The tumor was histopathologically diagnosed as a low-grade malignant GIST. SILS is a useful resection technique for small-intestinal GIST.

Rare case of lung abscess caused by a swallowed denture.

Accidentally swallowed dentures can cause serious complications when they are not diagnosed and treated promptly. We report an extremely rare case of a lung abscess caused by a swallowed complete denture. Chest computed tomography and endoscopic examination revealed that a swallowed denture migrated to the right upper lobe through an esophagopulmonary fistula, and a lung abscess developed. A life-saving and curative operation was performed with no significant postoperative complications. To the best of our knowledge, such a clinical condition has not yet been described in the literature.

FBXW7 mediates chemotherapeutic sensitivity and prognosis in NSCLCs.

UNLABELLED: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide. To improve the prognosis of patients with NSCLCs, new and validated therapeutic targets are critically needed. In this study, we focused on F-box and WD repeat domain containing-7 (FBXW7), an E3 ubiquitin ligase, that regulates the degradation of MCL1, Myc, cyclin E, and TOP2A. Importantly, loss of FBXW7 was associated with increased sensitivity of tumors to a class I-specific histone deacetylase (HDAC) inhibitor, MS-275. Immunohistochemical analysis revealed increased expression of FBXW7 targets, MCL1 and TOP2A, in NSCLC tumors with low expression of FBXW7. Moreover, clinical specimens exhibiting low FBXW7 expression presented with more progressive cancer and significantly shorter cancer-specific survival than patients with high FBXW7 expression. Mechanistic study of NSCLC cell lines with silenced FBXW7 revealed enhanced MS-275 sensitivity and taxol resistance. Interestingly, taxol resistance was eliminated by MS-275 treatment, suggesting the potential of HDAC inhibitors for the treatment of aggressive taxol-resistant NSCLCs that lack FBXW7. IMPLICATIONS: FBXW7 status impacts chemosensitivity and is a prognostic marker in NSCLCs. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/early/2013/12/19/1541-7786.MCR-13-0341/F1.large.jpg.

Preoperative 18F-fluorodeoxyglucose positron emission tomography can predict the tumor malignancy of small peripheral lung cancer.

PURPOSE: Recent advances in image diagnostic technology have enhanced the discovery of peripheral small size lung cancers. Here, we examined the utility of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for the evaluation of grade of tumor malignant potency. METHODS: Seventy-nine patients with peripheral small lung cancers (≤2 cm) who underwent surgical resections and preoperative FDG-PET were enrolled. The correlations between the maximum standardized uptake value (SUVmax) and various clinicopathological features related to tumor invasiveness, nodal metastasis, and recurrence were analyzed. RESULTS: The median SUVmax of all tumors was 2.4 (range, 0-16.1). The SUVmax was significantly higher in patients with vascular invasion (5.6 ± 3.5 vs. 2.4 ± 2.4; P <0.0001), lymphatic invasion (4.9 ± 3.7 vs. 2.7 ± 2.6; P = 0.0029), lymph node metastasis (6.1 ± 4.4 vs. 3.0 ± 2.7; P = 0.0022), and recurrences (5.8 ± 3.3 vs. 3.1 ± 3.1; P = 0.0219). Patients with SUVmax ≥2.5 had a significantly higher incidence rate of vascular invasion (56% vs. 7%; P <0.0001), lymphatic invasion (51% vs. 15%; P = 0.0006), lymph node metastasis (26% vs. 3%; P = 0.0033), and recurrence (18% vs. 3%; P = 0.0289). The patients with SUVmax ≥1.5 also had a significantly higher incidence of vascular invasion, lymphatic invasion, lymph node metastasis, and recurrence. It is particularly worth noting that patients with SUVmax <1.5 had no vascular invasion, lymph node metastasis, or recurrence. CONCLUSION: Preoperative SUVmax of peripheral small lung cancers were significantly associated with tumor malignancy.

Relapsed cervicomediastinal lymph node carcinoma with an unknown primary site treated with TS-1 alone: a case report.

BACKGROUND: Cervicomediastinal lymph node carcinoma with an unknown primary site is quite rare, and useful treatment of these diseases has not been established. We report here the case of a patient successfully treated with TS-1 alone after the relapse of cervicomediastinal lymph node carcinoma with an unknown primary site. CASE PRESENTATION: A 62-year-old man was referred to our hospital because of cervicomediastinal lymph node swelling and high serum levels of carbohydrate antigen 19-9 and carcinoembryonic antigen. Fluorodeoxyglucose-positron emission tomography/computed tomography revealed an accumulation of fluorodeoxyglucose in the left supraclavicular lymph nodes, mediastinal lymph nodes, and the pelvic cavity. Colonoscopy revealed rectal cancer, which was diagnosed by biopsy as a tubular adenocarcinoma. Because metastases from rectal cancer to the cervicomediastinal lymph nodes are rare, the patient underwent thoracoscopic mediastinal lymphadenectomy. A biopsy specimen from the paraaortic lymph nodes demonstrated papillary adenocarcinoma that was pathologically different from the rectal cancer; therefore, a diagnosis of mediastinal carcinoma with an unknown primary site was established. The patient underwent low anterior resection of the rectum for the rectal cancer, and no abdominal lymph node metastasis (pMP, N0/stage I) was found. Although radiotherapy was performed for the cervicomediastinal lymph nodes, the mediastinal carcinoma relapsed after 6 months. Because the patient desired oral chemotherapy on an outpatient basis, TS-1 was administered at a dosage of 80 mg/day for 2 weeks, followed by a 1-week rest. TS-1 treatment resulted in a decrease in the size of the cervicomediastinal lymph nodes, and the serum tumor marker levels decreased to normal after the fourth course. The patient continued TS-1 treatment without adverse events and is currently alive without recurrence or identification of the primary site at the 32nd month after TS-1 treatment. CONCLUSION: This is the first reported case of relapsed cervicomediastinal lymph node carcinoma with an unknown primary site treated by TS-1 alone. TS-1 treatment for the carcinoma with an unknown primary site may be useful in patients who are not candidates for systemic platinum-based chemotherapy.

Podoplanin overexpression in human mesothelioma cell lines enhances the tumorigenic phenotype.

Podoplanin, a small type I integral membrane mucin-type sialoglycoprotein, serves as a useful marker for diagnosing malignant pleural mesothelioma (MPM); however, the physiological function of podoplanin in mesothelioma cells is not known. To elucidate the role of podoplanin in the pathogenesis of MPM, we generated two mesothelioma cell lines (PODO1 and PODO2) that stably express high levels of podoplanin. Although PODO1 cells proliferated to the same extent in culture or in nude mice, the survival rate of the mice was significantly reduced compared with that of the controls. We demonstrated that PODO1 and PODO2 cells had increased invasive ability in in vitro assays and induced upregulation of matrix metalloproteinase-1. PODO1 and PODO2 cultures could not be induced to undergo apoptosis when starved or treated with cis-diamminedichloroplatinum(II) (CDDP) compared with the controls. Moreover, silencing of podoplanin expression using RNA interference restored the ability of CDDP to induce apoptosis. Consistent with their growth properties, we detected constitutive activation of extracellular signal-regulated kinase in PODO1 and PODO2 cultures. These findings suggest that constitutive expression of podoplanin contributes to the invasive growth properties of mesothelioma cells and their resistance to apoptosis. Moreover, our data suggest that podoplanin or components of its signaling pathway, or both, may serve as important targets for developing novel treatments for MPM.

Successful resection of a glomus tumor of the trachea.

Extracutaneous glomus tumors are uncommon, and their occurrence in the trachea is rare. We present a case of a surgically resected glomus tumor of the trachea in a 56-year-old woman who presented with worsening dyspnea and cough. Bronchoscopy and computed tomography showed a polypoid tumor arising from the posterior membrane of the lower trachea just above the carina; the tracheal lumen was approximately 80% occluded. The patient underwent successful tracheal sleeve resection with primary reconstruction. The histological characteristics and immunohistochemical profile were typical for this tumor. The clinicopathological features of this unusual neoplasm are discussed, and the literature is reviewed.

Successful management of a large bronchopleural fistula after lobectomy: report of a case.

The development of bronchopleural fistula after pulmonary resection is a well-known complication associated with a high mortality rate. We herein describe the successful management of a bronchopleural fistula using a rib and intercostal muscle in a patient with a large stump opening of 25 mm in diameter. A flap with rib and intercostal muscle is useful for large bronchopleural fistulas to avoid airway stenosis.

Pulmonary function after pulmonary resection by posterior thoracotomy, anterior thoracotomy or video-assisted surgery.

OBJECTIVE: Predicted postoperative forced expiratory volume in 1s (ppoFEV1) is estimated in lung cancer patients before pulmonary resection, as well as the clinical stage. This study aims to evaluate ppoFEV1 and ppo-vital capacity (ppoVC) on postoperative day 7 (POD7) and to compare the results following video-assisted thoracic surgery (VATS) and open thoracotomy procedures. METHODS: Of the 155 patients who underwent pulmonary resection, 70 had VATS; 30 had muscle-sparing thoracotomy (anterior limiting thoracotomy (AL)); and 55 had postero-lateral thoracotomy (PL). VC and FEV1 were measured on POD7 and compared with the VC and FEV1 before surgery using analysis of covariance (ANCOVA). The ratio of the actual- and the ppoVC and FEV1 was evaluated to identify factors associated with variations in postoperative residual VC/FEV1. RESULTS: There were significant differences by analysis of covariance (ANCOVA) in the VC/FEV1 among the three surgical approaches. In the VATS group, the VC ratio and the FEV1 ratio were 96.5% and 94.7%, respectively; they were significantly higher in the VATS group than in the thoracotomy group (AL: 90.4% and 90.1%, respectively; PL: 87.4% and 87.6%, respectively). Non-chronic obstructive pulmonary disease (COPD) and upper lobectomy were also associated with a low VC ratio and FEV1 ratio. CONCLUSION: Predicted postoperative pulmonary function might be overestimated in COPD patients or in those undergoing VATS or lower lobectomy.

Immunohistochemical analysis of phosphorylated epidermal growth factor receptor might provide a surrogate marker of EGFR mutation.

PURPOSE: Overexpression of EGFR is found in several malignancies including lung cancers. Recently, EGFR mutation has been shown to correlate with responsiveness to tyrosine kinase inhibitors (TKI). Although antibodies against phophorylated EGFR have been used in vitro, phosphorylated EGFR has yet not been examined well in resected non-small cell lung cancers (NSCLCs). EXPERIMENTAL DESIGN: We studied the immunohistochemistry of anti-EGFR and phosphorylated EGFR in 97 resected NSCLCs, examined the relationship with EGFR mutation, and performed quantitative RT-PCR of the EGFR gene in the TaqMan assay. RESULT: EGFR mutation was seen in 27% of 97 NSCLCs and 37% of 70 adenocarcinomas. EGFR was stained in 60% of 97 NSCLCs. Phosphorylation of tyrosine 845 (pY845) and 1068 (pY1068) was positive in 49% and 48%, respectively. The observed correlation with EGFR mutation and pY845 or pY1068 was statistically significant (P=0.0001 for pY845, P<0.0001 for pY1068, chi square test), although phospho-EGFR status was not associated with a particular mutation type. pY1068-positive tumors also correlated with female, light smoker, and adenocarcinoma histology, but not with mRNA expression. Moreover, patients with pY1068-positive tumors showed prolonged survival (P=0.0093, log-rank test). CONCLUSION: It is possible that immunohistochemistry of phosphorylated EGFR can substitute for EGFR mutation analysis. Further investigation is necessary to determine whether phospho-EGFR immunohistochemistry predicts response to TKIs and survival benefit.

l-type amino acid transporter 1 and CD98 expression in primary and metastatic sites of human neoplasms.

The significance of L-type amino acid transporter (LAT) 1 expression remains unclear in the metastatic process of human neoplasms, whereas experimental studies have demonstrated that LAT1 is associated with the metastatic process of cancer cells. We compared the immunohistochemical expression of LAT1 and CD98 between the primary site and a concordant pulmonary metastatic site in 93 cancer patients, all of whom had undergone thoracotomy. LAT1, CD98, Ki-67 labeling index, vascular endothelial growth factor (VEGF), CD31, and CD34 were analyzed by immunohistochemical staining in the resected tumors of 93 cancer patients: 45 colon cancers; nine breast cancers; eight head and neck cancers; 11 genital cancers; 14 soft-tissue sarcomas; and six other cancers. The expression of these markers was significantly higher in the metastatic sites than in the primary sites. In total, the positive rates of LAT1, CD98, Ki-67, VEGF, CD31, and CD34 were 40, 24, 56, 41, 45, and 39%, respectively, in the primary sites and 65, 45, 84, 67, 73, and 61%, respectively, in the metastatic sites. LAT1 expression was closely correlated with CD98 expression, angiogenesis, and cell proliferation. The association between LAT1 and CD98 expression was strongest in the primary and metastatic sites. The present study suggests that overexpression of LAT1 and CD98 has an important role to play in the metastatic process of variable human neoplasms. Moreover, LAT1 expression was significantly correlated with cell proliferation and angiogenesis.

Thymoma with ganglioneuroblastomatous component: case report.

A mediastinal tumor in a 49-year-old woman with myasthenia gravis is reported. The tumor was well-demarcated and located in the supero-anterior mediastinum. Microscopically, the tumor consisted of thymic and neuroblastic tumor components, the latter of which consisted of immature and maturing neuronal cells, abundant neuropils, and Schwannian stroma. The two components intermingled with each other inside the tumor capsule. The tumor was diagnosed as thymoma with a ganglioneuroblastomatous component. The coexistence of epithelial and neuronal tissues in the thymic neoplasm is extremely rare.

Fluorine-18-alpha-methyltyrosine positron emission tomography for diagnosis and staging of lung cancer: a clinicopathologic study.

PURPOSE: L-[3-(18)F]-alpha-methyltyrosine ([(18)F]FMT) is an amino acid tracer for positron emission tomography (PET). We evaluated the diagnostic usefulness of [(18)F]FMT PET in non-small-cell lung cancer (NSCLC) patients. Tumor uptake of [(18)F]FMT was compared with that of 2-[(18)F]-fluoro-2-deoxy-D-glucose ([(18)F]FDG) and correlated with L-type amino acid transporter 1 (LAT1) expression. EXPERIMENTAL DESIGN: Fifty NSCLC patients were enrolled in this study, and a pair of PET study with [(18)F]FMT and [(18)F]FDG was done. LAT1 expression and Ki-67 labeling index of the resected tumors were analyzed by immunohistochemical staining. RESULTS: For the primary tumor detection, [(18)F]FMT PET exhibited a sensitivity of 90% whereas the sensitivity for [(18)F]FDG PET was 94%. For lymph node staging, the sensitivity and specificity of [(18)F]FMT PET were 57.8% and 100%, and those of [(18)F]FDG PET were 65.7% and 91%, respectively. The expression of LAT1 in squamous cell carcinoma and large cell carcinoma was significantly higher than that in adenocarcinoma. [(18)F]FMT uptake was also higher in squamous cell carcinoma and large cell carcinoma than in adenocarcinoma. Uptake of [(18)F]FMT in the tumor is closely correlated with LAT1 expression (rho = 0.890). CONCLUSION: [(18)F]FMT PET had no false-positives in the detection of primary tumor and lymph node metastasis and could improve the diagnostic performance in NSCLC. Uptake of [(18)F]FMT correlated with the expression of LAT1 that showed a significant association with cellular proliferation.

CDX2 as a useful marker of colorectal adenocarcinoma metastases to lung in pre-operative biopsy specimens.

Although distinguishing metastatic colorectal adenocarcinoma from primary lung adenocarcinoma is often difficult, pre- or intra-operative identification is very important, as the resection areas for each diagnosis differ substantially. CDX2, a recently cloned homeobox gene, represents a highly specific and sensitive marker of colorectal adenocarcinoma. We evaluated CDX2 expression using pre- and intra-operative biopsy specimens. The study examined 50 consecutive colorectal adenocarcinoma metastases to the lung, including 20 biopsy specimens and 66 resected specimens, and 21 primary lung adenocarcinomas. All specimens were immunohistochemically stained for CDX2, cytokeratin (CK) 7, CK20 and thyroid transcription factor (TTF)-1, and scored in a semi-quantitative manner. Mean staining score in biopsy specimens was significantly higher for CDX2 than for CK20. Sensitivities for CDX2 and CK7-/20+ in biopsy specimens were 95.0 and 65.0%, respectively. If CDX2 immunostaining had not been performed, 8 biopsy specimens (40%), and 20 resected specimens (30.3%) might have been diagnosed as equivocal cases either as primary lung cancer or metastatic colorectal cancer, using other markers. These results suggest that positive CDX2 staining represents a highly sensitive and specific marker of metastatic colorectal carcinoma in both biopsy and resected specimens, and is superior to staining for the CK7-/20+ phenotype.

Phase II prospective study of the efficacy of gefitinib for the treatment of stage III/IV non-small cell lung cancer with EGFR mutations, irrespective of previous chemotherapy.

PURPOSE: Mutations in the epidermal growth factor receptor (EGFR) gene are associated with increased sensitivity of non-small cell lung cancer (NSCLC) to gefitinib, an EGFR tyrosine kinase inhibitor. The objective of this study was to prospectively evaluate the efficacy of gefitinib in patients with stage III/IV NSCLC whose tumors carried EGFR mutations, irrespective of previous chemotherapy. EXPERIMENTAL DESIGN: Genomic DNA was extracted from tumor specimens and EGFR mutations in exons 19 and 21 analyzed by direct sequencing. Patients with stage III/IV NSCLC whose tumors had the EGFR mutations received gefitinib (250 mg/day orally). Response, toxicity and survival data were assessed. RESULT: From November 2004-May 2006, 21 patients with EGFR mutations received gefitinib (median age: 59 years; 17 females; 19 non-smokers; all had adenocarcinomas). Two patients discontinued gefitinib and withdrew from the study 3 weeks after gefitinib initiation (interstitial pneumonitis, 1 patient; facial acne, 1 patient). Of 19 patients, 3 achieved complete response, 13 exhibited partial response and 3 had stable disease. Response and disease control rates were 76% (95% confidence interval [CI] 53-92) and 90% (95% CI 70-99), respectively. The most common adverse event was skin toxicity (67%); however, no grade 4 skin toxicities were seen. Ten patients relapsed and three died at a median follow-up period of 12.6 months (range 5.6-23.8 months); median progression-free survival was 12.9 months. CONCLUSION: Analysis of tumor EGFR mutations in patients with NSCLC could be used to identify patients suitable for treatment with gefitinib to obtain optimum response and disease control rates.

Expression of Foxp3 in non-small cell lung cancer patients is significantly higher in tumor tissues than in normal tissues, especially in tumors smaller than 30 mm.

Active suppression by CD4+CD25+ T regulatory cells (T regs) plays an important role in the down-regulation of T cell responses to foreign and self-antigens. Thus far, the potential role of T regs in human tumors has been reported. T reg-mediated suppression of antitumor immune responses may partly explain the poor clinical response to vaccine-based immunotherapy for human cancer. The forkhead transcription factor Foxp3 is a critical regulator of T regs development and function. Foxp3 represents a specific marker for the T regs. In this study, we measured the Foxp3 mRNA expression in tumors and in normal tissues from 46 patients with non-small cell lung carcinoma (NSCLC), and tumor tissues showed a significantly higher expression of Foxp3 mRNA than normal tissues. The expression of Foxp3 mRNA and the tumor diameter were inversely proportional. These results suggest that T regs expressing Foxp3 selectively accumulate in tumor tissues of NSCLC and contribute to antitumor immune dysfunction, especially in the early stages.