Efficacy of the MAGE-A3 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small-cell lung cancer (MAGRIT): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Fewer than half of the patients with completely resected non-small-cell lung cancer (NSCLC) are cured. Since the introduction of adjuvant chemotherapy in 2004, no substantial progress has been made in adjuvant treatment. We aimed to assess the efficacy of the MAGE-A3 cancer immunotherapeutic in surgically resected NSCLC. METHODS: In this randomised, double-blind, placebo-controlled trial, we recruited patients aged at least 18 years with completely resected stage IB, II, and IIIA MAGE-A3-positive NSCLC who did or did not receive adjuvant chemotherapy from 443 centres in 34 countries (Europe, the Americas, and Asia Pacific). Patients were randomly assigned (2:1) to receive 13 intramuscular injections of recMAGE-A3 with AS15 immunostimulant (MAGE-A3 immunotherapeutic) or placebo during 27 months. Randomisation and treatment allocation at the investigator site was done centrally via internet with stratification for chemotherapy versus no chemotherapy. Participants, investigators, and those assessing outcomes were masked to group assignment. A minimisation algorithm accounted for the number of chemotherapy cycles received, disease stage, lymph node sampling procedure, performance status score, and lifetime smoking status. The primary endpoint was broken up into three co-primary objectives: disease-free survival in the overall population, the no-chemotherapy population, and patients with a potentially predictive gene signature. The final analyses included the total treated population (all patients who had received at least one treatment dose). This trial is registered with ClinicalTrials.gov, number NCT00480025. FINDINGS: Between Oct 18, 2007, and July 17, 2012, we screened 13 849 patients for MAGE-A3 expression; 12 820 had a valid sample and of these, 4210 (33%) had a MAGE-A3-positive tumour. 2312 of these patients met all eligibility criteria and were randomly assigned to treatment: 1515 received MAGE-A3 and 757 received placebo and 40 were randomly assigned but never started treatment. 784 patients in the MAGE-A3 group also received chemotherapy, as did 392 in the placebo group. Median follow-up was 38·1 months (IQR 27·9-48·4) in the MAGE-A3 group and 39·5 months (27·9-50·4) in the placebo group. In the overall population, median disease-free survival was 60·5 months (95% CI 57·2-not reached) for the MAGE-A3 immunotherapeutic group and 57·9 months (55·7-not reached) for the placebo group (hazard ratio [HR] 1·02, 95% CI 0·89-1·18; p=0·74). Of the patients who did not receive chemotherapy, median disease-free survival was 58·0 months (95% CI 56·6-not reached) in those in the MAGE-A3 group and 56·9 months (44·4-not reached) in the placebo group (HR 0·97, 95% CI 0·80-1·18; p=0·76). Because of the absence of treatment effect, we could not identify a gene signature predictive of clinical benefit to MAGE-A3 immunotherapeutic. The frequency of grade 3 or worse adverse events was similar between treatment groups (246 [16%] of 1515 patients in the MAGE-A3 group and 122 [16%] of 757 in the placebo group). The most frequently reported grade 3 or higher adverse events were infections and infestations (37 [2%] in the MAGE-A3 group and 19 [3%] in the placebo group), vascular disorders (30 [2%] vs 17 [3%]), and neoplasm (benign, malignant, and unspecified (29 [2%] vs 16 [2%]). INTERPRETATION: Adjuvant treatment with the MAGE-A3 immunotherapeutic did not increase disease-free survival compared with placebo in patients with MAGE-A3-positive surgically resected NSCLC. Based on our results, further development of the MAGE-A3 immunotherapeutic for use in NSCLC has been stopped. FUNDING: GlaxoSmithKline Biologicals SA.

Prognostic value of the immunohistochemistry markers CD56, TTF-1, synaptophysin, CEA, EMA and NSE in surgically resected lung carcinoid tumors.

Lung carcinoid tumor is a type of neuroendocrine tumor, which is subdivided into typical carcinoid (TC) and atypical carcinoid (AT), based on the rate of mitosis and the presence of necrosis. Several prognostic factors for lung carcinoids have been reported in the literature, including the type, Ki67 index, stage, chemotherapy and radiation therapy. In the present study, 108 cases with resected carcinoid lung tumors were enrolled and the expression of CD56, thyroid transcription factor 1, synaptophysin, carcinoembryonic antigen, epithelial membrane antigen and neuron-specific enolase (NSE) in the resected tissue specimens was immunohistochemically analyzed. Patients with positive staining for NSE had an unfavorable survival prognosis compared with patients with negative staining for NSE (137.2 vs. 150.0 months, P=0.044). According to univariate analysis, none of the above immunohistochemistry markers was associated with survival, and according to multivariate analysis, NSE was an independent influencing factor for survival inpatients with AT (P=0.046) and furthermore, the stage was an independent factor of survival in patients with TC (P=0.005).

Simultaneous pathological findings in biopsy specimens of patients with surgically resected lung carcinoids and their role in survival.

Pulmonary carcinoid tumors are rare, low-grade malignant tumors that constitute 1-2% of all lung tumors. The present study aimed to describe the simultaneous pathological findings in biopsy specimens of patients with surgically resected lung carcinoids and determine their association with survival rates. For this purpose, 108 patients with resected carcinoid lung tumors were followed-up for 96 months and analyzed for simultaneous pathological findings in biopsy specimens. Among these, simultaneous pathological findings were found in 82 patients. The association between these findings and patient survival rates was evaluated. Atelectasis was a simultaneous finding in 52.4% of the patients, desquamative interstitial pneumonia (DIP) in 13.4%, emphysema in 24.4% and bronchiectasis in 9.8%. The survival rate was 100% for the patients with atelectasis, 81.8% for the patients with DIP, 90% for the patients with emphysema and 75% for the patients with bronchiectasis (P<0.05). According to the univariate analysis, the type of carcinoid was associated with patient survival with better survival rates for patients with typical carcinoids, while age, sex, stage and simultaneous pathological findings were not associated with patient survival. On the whole, there was a statistically significant difference in the survival rates of patients with resected lung carcinoids with different simultaneous pathological findings. However, further studies are warranted to assess the role of these findings in the survival of these patients.

Predictive Indicators of Survival in Patients With Surgically Resected Lung Carcinoid Tumors at a Greek Medical Center.

Introduction Lung carcinoid tumors are neuroendocrine neoplasms, less frequent than other lung tumors. They are subdivided into typical carcinoids (TC) and atypical carcinoids (AC), according to the rate of mitosis and the presence of necrosis. Lung carcinoids are often asymptomatic and only discovered incidentally. They may also present with cough, wheezing, asthma, and chronic obstructive pulmonary disease, chest pain, and hemoptysis depending on the location of the tumor and, less commonly, present with carcinoid syndrome. In our study, we describe the clinical and pathological features of patients with surgically resected lung carcinoids at our institution over a period of 14 years. We also examine if these features, including age, gender, tumor size, type of carcinoid, stage, nodal involvement, and Ki-67 expression are associated with patients' survival. Materials and methods We retrospectively reviewed patients that underwent surgery with a final histologic diagnosis of a pulmonary carcinoid tumor from March 2005 to March 2019. The evaluation included history, physical examination, chest radiographs, computerized tomography of the chest, upper abdomen, and brain, and bone scintiscan. All specimens resected during the surgical procedures were sent for pathological examination, including mediastinal and hilar lymph nodes. The patients' age, gender, tumor size, type of carcinoid, nodal involvement, stage, and Ki-67 expression were recorded and correlated to the patients' survival rates. Results The study included 108 patients - 52 males and 56 females - with a mean age of 51.5 years (range 11-80 years). Atypical carcinoid was the diagnosis in 28 patients (16 males and 12 females) and 80 patients had the diagnosis of typical carcinoid (36 males and 44 females). Tumor size was ≤3.7 cm in 84 patients (68 with TC and 16 with AC) and >3.7 cm in 22 patients (12 with TC and 10 with AC). Sixteen patients had nodal deposits, 12 in N1 nodes and four in N2 nodes. Eighty patients were classified in stage I, 18 patients in stage II, and 10 patients in stage III. None of the patients had distant metastases. The Ki-67 proliferation index was examined in 84 specimens and Ki-67 was <2.5 in 50 patients and ≥2.5 in 34 patients. Of the 108 patients, eight died, all with disease-related death. According to the Cox regression univariate analysis, four factors were correlated to shorter survival: atypical histology, tumor size >3.7 cm, nodal involvement, and advanced stage Conclusions In conclusion, we found that histological type, tumor size, nodal involvement, and stage are associated with survival in patients with surgically resected lung carcinoids without distant metastases. Other parameters, such as age at operation, gender, and Ki-67 index, did not have a role in survival in these patients according to the Cox regression univariate analysis.

Microsatellite instability and loss of heterozygosity at the MEN1 locus in lung carcinoid tumors: a novel approach using real-time PCR with melting curve analysis in histopathologic material.

The possible causes and genetic mechanisms of pulmonary carcinoid tumor development are unclear. In this study, we examined genetic alterations at the MEN1 locus in archival material from 15 pulmonary carcinoids. We employed, for the first time in this setting, real-time PCR with melting curve analysis in order to identify loss of heterozygosity (LOH) or microsatellite instability (MI) in two polymorphic markers (PYGM, D11S449) at the MEN1 locus and one additional marker (D11S906) of a putative oncosuppressive region distal to the MEN1 gene. Sequencing data were available in a selected subset of tumors in order to verify the reliability of real-time PCR analysis. We observed LOH at PYGM in 38% of the cases and MI in 13.3% of the cases. Our data indicate that real-time PCR with melting curve analysis is a reliable technique for LOH and MI detection and indicate that genetic errors at the MEN1 locus but also distal to it may be involved in the development of sporadic pulmonary carcinoid tumors.

Determination of EGFR and KRAS mutational status in Greek non-small-cell lung cancer patients.

It has been reported that certain patients with non-small-cell lung cancer (NSCLC) that harbor activating somatic mutations within the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene may be effectively treated using targeted therapy. The use of EGFR inhibitors in patient therapy has been demonstrated to improve response and survival rates; therefore, it was suggested that clinical screening for EGFR mutations should be performed for all patients. Numerous clinicopathological factors have been associated with EGFR and Kirsten-rat sarcoma oncogene homolog (KRAS) mutational status including gender, smoking history and histology. In addition, it was reported that EGFR mutation frequency in NSCLC patients was ethnicity-dependent, with an incidence rate of ~30% in Asian populations and ~15% in Caucasian populations. However, limited data has been reported on intra-ethnic differences throughout Europe. The present study aimed to investigate the frequency and spectrum of EGFR mutations in 1,472 Greek NSCLC patients. In addition, KRAS mutation analysis was performed in patients with known smoking history in order to determine the correlation of type and mutation frequency with smoking. High-resolution melting curve (HRM) analysis followed by Sanger sequencing was used to identify mutations in exons 18-21 of the EGFR gene and in exon 2 of the KRAS gene. A sensitive next-generation sequencing (NGS) technology was also employed to classify samples with equivocal results. The use of sensitive mutation detection techniques in a large study population of Greek NSCLC patients in routine diagnostic practice revealed an overall EGFR mutation frequency of 15.83%. This mutation frequency was comparable to that previously reported in other European populations. Of note, there was a 99.8% concordance between the HRM method and Sanger sequencing. NGS was found to be the most sensitive method. In addition, female non-smokers demonstrated a high prevalence of EGFR mutations. Furthermore, KRAS mutation analysis in patients with a known smoking history revealed no difference in mutation frequency according to smoking status; however, a different mutation spectrum was observed.

Primary Malignant Melanoma of the Lung: A Case Report.

BACKGROUND: Primary melanoma of the lung is an extremely rare pathological entity and sparsely reported in the literature. CASE PRESENTATION: A case of primary malignant melanoma of the lung in a 41-year-old female is reported. The clinical, radiological and histopathological features are discussed. The initial symptom was cough, whereas the chest radiography showed a round opacity of the right lung. The computed tomography of the chest revealed a well-demarcated mass lesion in the right upper lobe. Endobronchial mass causing obstruction of the upper lobar bronchus was the bronchoscopic finding. Patient underwent pneumonectomy. A diagnosis of melanoma was confirmed postoperatively after the immunohistochemistry. Primary nature of the tumour in the lung results from the demonstration of characteristic junctional pattern of melanoma cells beneath the bronchial epithelium on histopathology, and from exclusion of other potential primary sites in the clinical, paraclinical and laboratory examination. CONCLUSIONS: Primary melanoma of the lung represents a rare pathological entity. Careful interpretation of histopathological information in correlation with all other findings from clinical and paraclinical studies can establish a diagnosis. Follow-up is necessary in order to diagnose potential dissemination or secondary sites of the disease. Due to the small number of cases reported in the literature, there is no experience on the management and the prognosis of the disease, but surgical resection remains the cornerstone of the treatment.

hMSH2 and hMLH1 gene expression patterns differ between lung adenocarcinoma and squamous cell carcinoma: correlation with patient survival and response to adjuvant chemotherapy treatment.

BACKGROUND: We recently showed that the mRNA levels of mismatch repair (MMR) proteins in non-small cell lung carcinoma (NSCLC) tissue specimens and the phenotypic translation of molecular MMR data refines the biology of the MMR system with consequent diagnostic implications in the clinical assessment of lung cancer patients. METHODS: hMLH1 and hMSH2 mRNA expression was previously evaluated by qPCR for 29 NSCLC patients (13 with squamous cell carcinoma [SQC] and 16 with adenocarcinoma [ADC]) and MMR mRNA levels were converted into clinically distinct phenotypic entities. In this study, we evaluated the correlation of the hMSH2 and hMLH1 mRNA phenotypes with patient survival and their response to adjuvant chemotherapy. RESULTS: hMSH2 and hMLH1 mRNA phenotypic distribution differed between SQC and ADC. The MMR phenotypes differed also between advanced and early stage SQC. SQC patients with an increased hMSH2 expression had a better outcome than patients with a reduced hMSH2 expression. However, ADC patients with an increased hMSH2 expression had a poor outcome compared to those with low hMSH2 levels. SQC patients with a high hMSH2 expression exhibited a better response to adjuvant chemotherapy, whereas ADC patients with high hMSH2 levels had a poor response. ADC patients with low hMSH2 levels showed good response to adjuvant chemotherapy compared to SQC patients bearing the same phenotypic profile. CONCLUSIONS: Our findings show that MMR mRNA phenotypes may be added to the known biological differences between SQC and ADC. hMLH1 and hMSH2 phenotypes distributed differently according to the NSCLC stage. Distinct MMR mRNA phenotypes in SQC and ADC corresponded to patient response to adjuvant chemotherapy.

Adjuvant MAGE-A3 immunotherapy in resected non-small-cell lung cancer: phase II randomized study results.

PURPOSE: The MAGE-A3 protein is expressed in approximately 35% of patients with resectable non-small-cell lung cancer (NSCLC). Several immunization approaches against the MAGE-A3 antigen have shown few, but often long-lasting, clinical responses in patients with metastatic melanoma. PATIENTS AND METHODS: A double-blind, randomized, placebo-controlled phase II study was performed assessing clinical activity, immunologic response, and safety following immunization with recombinant MAGE-A3 protein combined with an immunostimulant (13 doses over 27 months) in completely resected MAGE-A3-positive stage IB to II NSCLC. The primary end point was disease-free interval (DFI). RESULTS: Patients were randomly assigned to either MAGE-A3 immunotherapeutic (n = 122) or placebo (n = 60). After a median postresection period of 44 months, recurrence was observed in 35% of patients in the MAGE-A3 arm and 43% in the placebo arm. No statistically significant improvement in DFI (hazard ratio [HR], 0.75, 95% CI, 0.46 to 1.23; two-sided P = .254), disease-free survival (DFS; HR, 0.76; 95% CI, 0.48 to 1.21; P = .248), or overall survival (HR, 0.81; 95% CI, 0.47 to 1.40; P = .454) was observed. Corresponding analysis after a median of 70 months of follow-up revealed a similar trend for DFI and DFS. All patients receiving the active treatment showed a humoral immune response to the MAGE-A3 antigen, although no correlation was observed with outcome. No significant toxicity was observed. CONCLUSION: In this early development study with a limited number of patients, postoperative MAGE-A3 immunization proved to be feasible with minimal toxicity. These results are being investigated further in a large phase III study.

Mouse p53-deficient cancer models as platforms for obtaining genomic predictors of human cancer clinical outcomes.

Mutations in the TP53 gene are very common in human cancers, and are associated with poor clinical outcome. Transgenic mouse models lacking the Trp53 gene or that express mutant Trp53 transgenes produce tumours with malignant features in many organs. We previously showed the transcriptome of a p53-deficient mouse skin carcinoma model to be similar to those of human cancers with TP53 mutations and associated with poor clinical outcomes. This report shows that much of the 682-gene signature of this murine skin carcinoma transcriptome is also present in breast and lung cancer mouse models in which p53 is inhibited. Further, we report validated gene-expression-based tests for predicting the clinical outcome of human breast and lung adenocarcinoma. It was found that human patients with cancer could be stratified based on the similarity of their transcriptome with the mouse skin carcinoma 682-gene signature. The results also provide new targets for the treatment of p53-defective tumours.

Phenotypic mismatch repair hMSH2 and hMLH1 gene expression profiles in primary non-small cell lung carcinomas.

BACKGROUND: Defects in the human DNA mismatch repair genes (MMR) hMSH2 and hMLH1 are responsible for the development of sporadic and hereditary colorectal cancers. The role of MMR genes in the pathogenesis of lung cancer has not been elucidated. The aim of this study was to address the phenotypic mRNA expression profiles of mismatch DNA repair system in lung cancer. MATERIALS AND METHODS: We evaluated the mRNA levels of the hMSH2 and hMLH1 components of the mismatch DNA repair (MMR) system in 29 unselected frozen pairs of primary non-small cell lung carcinomas (NSCLCs) and their adjacent normal tissue (ANTs) specimens by quantitative real-time PCR analysis relative to housekeeping Porphobilinogen deaminase (hPBGD) mRNA. To simplify and potentially improve the analysis of data, we defined for each individual MMR mRNA two possible phenotypes: a regular (R(2): hMSH2/hPBGD mRNAs> or =1 and R(1): hMLH1/hPBGD mRNAs> or =1) and a reduced (r(2): hMSH2/hPBGD mRNAs<1 and r(1): hMLH1/hPBGD mRNAs<1). The presence of MMR gene expression was evaluated after conversion of the molecular mRNA levels into clinically distinct phenotypic entities by these working criteria, based on the hypothesis that reduced mRNA and protein levels result in lower or non-functional MMR. RESULTS: Phenotyping defined four distinct MMR system expression profiles, R(2)R(1), r(2)R(1), R(2)r(1) and r(2)r(1) by ascending tumor progression rate and identified a previously unrecognized disease-associated phenotypic entity (r(2)r(1)). The phenotype-based biological aspects of the MMR system suggested that its two components: (1) function independently and (2) are not directly involved in the onset of the transformation process, since healthy lung tissue was devoid of r(2)r(1) phenotypes. CONCLUSION: These findings link MMR mRNA levels of paired lung tissue specimens to patients' clinical condition and suggest that phenotypic translation of molecular MMR data refines the biology of the MMR system with consequent diagnostic implications in the clinical assessment of lung cancer patients.

Co-expression patterns of tumor-associated antigen genes by non-small cell lung carcinomas: implications for immunotherapy.

BACKGROUND: Polyvalent vaccination represents a recent attempt to improve the effectiveness of lung cancer immunotherapy. This study aimed to investigate whether a gene expression pattern of tumor-associated antigens (TAA) would exist indicating that their use will be most appropriate for the polyvalent vaccination of Caucasian non-small cell lung carcinoma (NSCLC) patients. We examined the concomitant expression of genes belonging to different TAA families for which expression frequencies either have never been detected in NSCLC or vary widely in the literature. RESULTS: 15/23 (65%) and 8/23 (35%) tumor samples were found expressing 6-11 and 2-5 out of the 12 examined TAAs, respectively, at levels >1% of the testis reference sample. The most prevalent TAA patterns observed were those of survivin standard (survivin-std)/survivin-2B expressed by 22/23 (95.5%) tumor samples and of survivin-std/survivin-2B/hTERT expressed by 19/23 (82.5%) tumor samples. The expression levels of the survivin-std gene strongly positively correlated to those of the survivin-2B (p=0.001) and the hTERT genes (p=0.031). The number of concomitantly expressed genes was found to be positively correlated to the age of the patients (p=0.001) and the tumor size (p=0.048). METHODS: Tumor material from 23 patients with NSCLC (12 adenocarcinomas, 8 squamous cell carcinomas, 3 bronchiolo-carcinomas) was examined. mRNA transcripts were detected for 5 genes of the survivin family, 5 MAGE-A genes as well as the genes of human telomerase reverse transcriptase (hTERT) and p53, by the use of quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) or semi-quantitative RT-PCR. CONCLUSION: This study provides evidence that, in Caucasian patients with NSCLC, highly prevalent expression patterns of TAA genes, predominantly of overexpressed TAAs, do exist. This result implies that the combined use of these TAA could help in designing more effective NSCLC immunotherapeutic protocols.

Cisplatin-based three drugs combination (NIP) as induction and adjuvant treatment in locally advanced non-small cell lung cancer: final results.

INTRODUCTION: This phase III trial was conducted in non-small cell lung cancer patients with locally advanced stage II B (only T3N0) III A and III B (only T4 N0). Primary endpoint was 2-year survival; secondary were toxicity, disease-free survival, and overall survival. METHODS: After three cycles of vinorelbine (N) 25 mg/m2 on days 1 and 5, ifosfamide/mesna (I) 3 g/m2 on day 1, cisplatin (P) (NIP), patients were treated by surgery and within 45 days were randomized to two additional cycles of NIP versus observation. RESULTS: Median tumor diameter was 5.5 cm (1.2-10.6). Overall, 155 of 156 patients received chemotherapy: 133 (85%) men, median age: 59 years (35-75). Sixty-five percentage of patients were stage III A, 28% II B, and 7% III B. The study has been closed prematurely because of the low inclusion rate. After three cycles of induction in 143 assessable patients, 82 reported an objective response (57.3%) (95% CI: 48.8-65.6), with 3.5% complete response and 53.8% partial response. Relative dose intensity during neoadjuvant NIP (%) was 97, 98, and 98.5 for vinorelbine, ifosfamide/mesna, and cisplatin, respectively. Tolerance: G3 to 4 neutropenia in 3% of patients and G3 to 4 anemia in 4%; nonhematological toxicities included G3 nausea/vomiting in 11%, G3 anorexia and G3 to 4 infection in 6.5%, G3 asthenia in 10% and G3 to 4 alopecia in 25.5%. After a median of 32 days after NIP, 107 patients (69%) underwent operation with complete resection (R0) in 74% (79 of 107 patients). Downstaging (N2 to N0) after surgery was 29%. Operative mortality rate was 2.8%. Twenty-one days (median) after surgery, 79 patients were randomized to adjuvant NIP (47%) or control (53%). Tolerance of adjuvant NIP: 12.5% G3 to 4 nausea/vomiting, 19% G3 alopecia, 6% G3 infection, and G3 asthenia. Overall median survival 32.3 versus 31.8 months in the observation and NIP arms, respectively. CONCLUSIONS: NIP allows 74% of R0 with no surgery delay. The few number of randomized patients did not allow to conclude on the efficacy of adjuvant chemotherapy.

Surgical resection of esthesioneuroblastoma metastasis to the chest wall.

A 51-year-old female patient was evaluated for a painful chest wall mass causing atelectasis of the right lung, pleural effusion, and dyspnea. The patient's history was significant for esthesioneuroblastoma at the age of 24; multiple recurrences of the tumor had been treated with surgery, radiotherapy, and chemotherapy. Surgical resection of the chest wall mass relieved her symptoms and improved her quality of life. Histologic examination confirmed metastatic esthesioneuroblastoma. The patient developed generalized disease and finally died 2 years after surgery. This case demonstrates the long natural history of this rare neoplasm and the need for close follow-up of patients so that they can be treated early.

Indoleamine 2,3-dioxygenase (IDO) expression in lung cancer.

BACKGROUND: The expression of indoleamine 2,3-dioxygenase (IDO) by tumor cells has been considered as a major tumor immune escape mechanism. The aim of this study was to investigate the expression of IDO in lung cancer cell lines as well as in surgically resected lung cancer specimens comparing the latter, to the expression in autologous samples from the corresponding non malignant lung tissue. Correlations of IDO expression with clinicopathological parameters of the disease were performed. METHODS: Nine human lung cancer cell lines and 28 patients with various types of primary lung cancer were enrolled in the study. IDO expression was determined by quantitative real-time PCR using a sample of lung hamartoma as reference. RESULTS: IDO expression was detected in all but three patients' tumor samples, in all but four autologous non malignant lung tissues and in three out of the nine cell lines that were examined. The relative expression of IDO in lung cancer cell lines (4.7 +/- 11.1) was significantly lower than that of all patients' tumor samples (p = 0.006) as well as than that of the autologous non affected lung tissues (p = 0.027). No statistically significant differences were noted between ADC and SCC regarding either the tumor samples or the autologous non affected samples. No significant correlations between IDO expression and clinicopathological parameters were found. CONCLUSION: Direct evidence is provided demonstrating that IDO mRNA can be constitutively expressed by lung cancer cells. The higher IDO expression observed in patients' samples can be attributed to the production of the enzyme by other cells recruited in the tumor microenvironment and the peri-tumoral lung area and/or to its induction by soluble factors of tumor origin.

Desmoid tumors of the chest wall.

Chest wall desmoid tumors (DT) are rare pathologic entities with microscopic features similar to, or undistinguishable from, fibromas or fibrosarcomas. From 1996 to 2001, four patients with DT were surgically managed in our department. Their ages ranged from 27 years to 43 years (mean 32.25 years, median 29.5 years). A resection of the lesion was performed with negative margins of 4 cm around the tumor (wide resection). A reconstruction of the chest wall was also performed with polytetrafluoroethylene (PTFE) in 2 patients and methylmethacrolate with Marlex mesh in 1 patient. One patient had a recurrence 15 months later, and was admitted for complementary resection, and remains disease-free for 5 years. The rest 3 patients are disease-free for 6 months to 5 years. Resection must include all adjacent, overlying and underlying musculature as well as soft tissues and any spare skin from the procedure should be used. Prognosis after a wide resection is good.