42 results on '"Incarbone, Matteo"'
Search Results
2. Navigating resistance to ALK inhibitors in the lorlatinib era: a comprehensive perspective on NSCLC.
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Gemelli, Maria, Albini, Adriana, Catalano, Gianpiero, Incarbone, Matteo, Cannone, Maria, Balladore, Emanuela, Ricotta, Riccardo, and Pelosi, Giuseppe
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ANAPLASTIC lymphoma kinase ,NON-small-cell lung carcinoma - Abstract
The emergence of anaplastic lymphoma kinase (ALK) rearrangements in non-small cell lung cancer (NSCLC) has revolutionized targeted therapy. This dynamic landscape, featuring novel ALK inhibitors and combination therapies, necessitates a profound understanding of resistance mechanisms for effective treatment strategies. Recognizing two primary categories – on-target and off-target resistance – underscores the need for comprehensive assessment. This review delves into the intricacies of resistance to ALK inhibitors, exploring complexities in identification and management. Molecular testing, pivotal for early detection and accurate diagnosis, forms the foundation for patient stratification and resistance management. The literature search methodology involved comprehensive exploration of Pubmed and Embase. The multifaceted perspective encompasses new therapeutic horizons, ongoing clinical trials, and their clinical implications post the recent approval of lorlatinib. Our expert opinion encapsulates the critical importance of understanding resistance mechanisms in the context of ALK inhibitors for shaping successful treatment approaches. With a focus on molecular testing and comprehensive assessment, this review contributes valuable insights to the evolving landscape of NSCLC therapy. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Cigarette smoke alters the transcriptome of non-involved lung tissue in lung adenocarcinoma patients
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Pintarelli, Giulia, Noci, Sara, Maspero, Davide, Pettinicchio, Angela, Dugo, Matteo, De Cecco, Loris, Incarbone, Matteo, Tosi, Davide, Santambrogio, Luigi, Dragani, Tommaso A., and Colombo, Francesca
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- 2019
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4. Lung Adenocarcinoma Diagnosed at a Younger Age Is Associated with Advanced Stage, Female Sex, and Ever-Smoker Status, in Patients Treated with Lung Resection.
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Dragani, Tommaso A., Muley, Thomas, Schneider, Marc A., Kobinger, Sonja, Eichhorn, Martin, Winter, Hauke, Hoffmann, Hans, Kriegsmann, Mark, Noci, Sara, Incarbone, Matteo, Tosi, Davide, Franzi, Sara, and Colombo, Francesca
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ADENOCARCINOMA ,LUNG cancer ,CONFIDENCE intervals ,EARLY detection of cancer ,LUNG tumors ,SEX distribution ,TUMOR classification ,AGE factors in disease ,DESCRIPTIVE statistics ,RESEARCH funding ,SMOKING ,DATA analysis software ,ODDS ratio - Abstract
Simple Summary: Since the factors influencing age at diagnosis of lung adenocarcinoma are unknown, in our study, we examined the relationships of age at diagnosis with smoking habit, clinical stage of disease, and sex in Italian and German patients with lung adenocarcinoma who underwent lung adenocarcinoma resection. Our results indicated that smoking habit, advanced clinical stage (more aggressive and larger tumour), and female sex were variables associated with younger age at diagnosis. This study provides new findings on the clinical variables influencing age at diagnosis of lung adenocarcinoma and paves the way for studies on the genetic and molecular mechanisms responsible for these associations. To date, the factors which affect the age at diagnosis of lung adenocarcinoma are not fully understood. In our study, we examined the relationships of age at diagnosis with smoking, pathological stage, sex, and year of diagnosis in a discovery (n = 1694) and validation (n = 1384) series of lung adenocarcinoma patients who had undergone pulmonary resection at hospitals in the Milan area and at Thoraxklinik (Heidelberg), respectively. In the discovery series, younger age at diagnosis was associated with ever-smoker status (OR = 1.5, p = 0.0035) and advanced stage (taking stage I as reference: stage III OR = 1.4, p = 0.0067; stage IV OR = 1.7, p = 0.0080), whereas older age at diagnosis was associated with male sex (OR = 0.57, p < 0.001). Analysis in the validation series confirmed the ever versus never smokers' association (OR = 2.9, p < 0.001), the association with highest stages (stage III versus stage I OR = 1.4, p = 0.0066; stage IV versus stage I OR = 2.0, p = 0.0022), and the male versus female sex association (OR = 0.78, p = 0.032). These data suggest the role of smoking in affecting the natural history of the disease. Moreover, aggressive tumours seem to have shorter latency from initiation to clinical detection. Finally, younger age at diagnosis is associated with the female sex, suggesting that hormonal status of young women confers risk to develop lung adenocarcinoma. Overall, this study provided novel findings on the mechanisms underlying age at diagnosis of lung adenocarcinoma. [ABSTRACT FROM AUTHOR]
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- 2023
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5. Genetic predisposition to lung adenocarcinoma outcome is a feature already present in patients' noninvolved lung tissue.
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Minnai, Francesca, Noci, Sara, Chierici, Marco, Cotroneo, Chiara Elisabetta, Bartolini, Barbara, Incarbone, Matteo, Tosi, Davide, Mattioni, Giovanni, Jurman, Giuseppe, Dragani, Tommaso A., and Colombo, Francesca
- Abstract
Emerging evidence suggests that the prognosis of patients with lung adenocarcinoma can be determined from germline variants and transcript levels in nontumoral lung tissue. Gene expression data from noninvolved lung tissue of 483 lung adenocarcinoma patients were tested for correlation with overall survival using multivariable Cox proportional hazard and multivariate machine learning models. For genes whose transcript levels are associated with survival, we used genotype data from 414 patients to identify germline variants acting as cis‐expression quantitative trait loci (eQTLs). Associations of eQTL variant genotypes with gene expression and survival were tested. Levels of four transcripts were inversely associated with survival by Cox analysis (CLCF1, hazard ratio [HR] = 1.53; CNTNAP1, HR = 2.17; DUSP14, HR = 1.78; and MT1F: HR = 1.40). Machine learning analysis identified a signature of transcripts associated with lung adenocarcinoma outcome that was largely overlapping with the transcripts identified by Cox analysis, including the three most significant genes (CLCF1, CNTNAP1, and DUSP14). Pathway analysis indicated that the signature is enriched for ECM components. We identified 32 cis‐eQTLs for CNTNAP1, including 6 with an inverse correlation and 26 with a direct correlation between the number of minor alleles and transcript levels. Of these, all but one were prognostic: the six with an inverse correlation were associated with better prognosis (HR < 1) while the others were associated with worse prognosis. Our findings provide supportive evidence that genetic predisposition to lung adenocarcinoma outcome is a feature already present in patients' noninvolved lung tissue. [ABSTRACT FROM AUTHOR]
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- 2023
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6. Germline polymorphisms and survival of lung adenocarcinoma patients: A genome-wide study in two European patient series
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Galvan, Antonella, Colombo, Francesca, Frullanti, Elisa, Dassano, Alice, Noci, Sara, Wang, Yufei, Eisen, Timothy, Matakidou, Athena, Tomasello, Luisa, Vezzalini, Marzia, Sorio, Claudio, Dugo, Matteo, Ambrogi, Federico, Iacobucci, Ilaria, Martinelli, Giovanni, Incarbone, Matteo, Alloisio, Marco, Nosotti, Mario, Tosi, Davide, Santambrogio, Luigi, Pelosi, Giuseppe, Pastorino, Ugo, Houlston, Richard S., and Dragani, Tommaso A.
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- 2015
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7. Lung cancer screening with spiral CT: Baseline results of the randomized DANTE trial
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Infante, Maurizio, Lutman, Fabio Romano, Cavuto, Silvio, Brambilla, Giorgio, Chiesa, Giuseppe, Passera, Eliseo, Angeli, Enzo, Chiarenza, Maurizio, Aranzulla, Giuseppe, Cariboni, Umberto, Alloisio, Marco, Incarbone, Matteo, Testori, Alberto, Destro, Anna, Cappuzzo, Federico, Roncalli, Massimo, Santoro, Armando, and Ravasi, Gianluigi
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- 2008
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8. Parietal Pleura-Based Malignant Perivascular Epithelioid Cell Neoplasm Protruding Into Serous Cavity: A Hitherto Unrecognized Occurrence
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Pelosi, Giuseppe, Sabella, Giovanna, Cannone, Maria, Balladore, Emanuela, Papanikolaou, Nikolaos, Incarbone, Matteo, Zompatori, Maurizio, Harari, Sergio, and Bedini, Amedeo Vittorio
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- 2020
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9. Gene expression signature of non-involved lung tissue associated with survival in lung adenocarcinoma patients
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Galvan, Antonella, Frullanti, Elisa, Anderlini, Marco, Manenti, Giacomo, Noci, Sara, Dugo, Matteo, Ambrogi, Federico, De Cecco, Loris, Spinelli, Roberta, Piazza, Rocco, Pirola, Alessandra, Gambacorti-Passerini, Carlo, Incarbone, Matteo, Alloisio, Marco, Tosi, Davide, Nosotti, Mario, Santambrogio, Luigi, Pastorino, Ugo, and Dragani, Tommaso A.
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- 2013
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10. Giant Secondary Overgrowth of Type-1 Pulmonary Cystic Airway Malformation Upon Development of Anaplastic Lymphoma Kinase–Rearranged Adenocarcinoma
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Pelosi, Giuseppe, Vandoni, Andrea, Meroni, Alberto, Uslenghi, Elisabetta, Callipo, Fabio, Papanikolaou, Nikolaos, Cannone, Maria, Balladore, Emanuela, D’Amico, Maria Emilia, Harari, Sergio, Zompatori, Maurizio, and Incarbone, Matteo
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- 2019
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11. Multiple isoforms and differential allelic expression of CHRNA5 in lung tissue and lung adenocarcinoma
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Falvella, Felicia S., Alberio, Tiziana, Noci, Sara, Santambrogio, Luigi, Nosotti, Mario, Incarbone, Matteo, Pastorino, Ugo, Fasano, Mauro, and Dragani, Tommaso A.
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- 2013
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12. The role of hepatic metastases and pulmonary tumor burden in predicting survival after complete pulmonary resection for colorectal cancer
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Sclafani, Francesco, Incarbone, Matteo, Rimassa, Lorenza, Personeni, Nicola, Giordano, Laura, Alloisio, Marco, and Santoro, Armando
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- 2013
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13. Association of lung adenocarcinoma clinical stage with gene expression pattern in noninvolved lung tissue
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Frullanti, Elisa, Colombo, Francesca, Falvella, Felicia S., Galvan, Antonella, Noci, Sara, De Cecco, Loris, Incarbone, Matteo, Alloisio, Marco, Santambrogio, Luigi, Nosotti, Mario, Tosi, Davide, Pastorino, Ugo, and Dragani, Tommaso A.
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- 2012
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14. p95HER2 Truncated Form in Resected Non-small Cell Lung Cancer
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Cappuzzo, Federico, Cho, Yong Gon, Sacconi, Andrea, Alì, Greta, Siclari, Olimpia, Incarbone, Matteo, Destro, Annarita, Terracciano, Luigi, Fontanini, Gabriella, Marchetti, Antonio, Roncalli, Massimo, and Varella-Garcia, Marileila
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- 2012
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15. Insulin-like growth factor-1 receptor and phosphorylated AKT-serine 473 expression in 132 resected thymomas and thymic carcinomas
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Zucali, Paolo A., Petrini, Iacopo, Lorenzi, Elena, Merino, Maria, Cao, Liang, Di Tommaso, Luca, Lee, Hye Seung, Incarbone, Matteo, Walter, Beatriz A., Simonelli, Matteo, Roncalli, Massimo, Santoro, Armando, and Giaccone, Giuseppe
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- 2010
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16. Genome-wide association study in discordant sibships identifies multiple inherited susceptibility alleles linked to lung cancer
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Galvan, Antonella, Falvella, Felicia S., Frullanti, Elisa, Spinola, Monica, Incarbone, Matteo, Nosotti, Mario, Santambrogio, Luigi, Conti, Barbara, Pastorino, Ugo, Gonzalez-Neira, Anna, and Dragani, Tommaso A.
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- 2010
17. FGFR4 Gly388Arg polymorphism may affect the clinical stage of patients with lung cancer by modulating the transcriptional profile of normal lung
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Falvella, Felicia S., Frullanti, Elisa, Galvan, Antonella, Spinola, Monica, Noci, Sara, De Cecco, Loris, Nosotti, Mario, Santambrogio, Luigi, Incarbone, Matteo, Alloisio, Marco, Calabrò, Elisa, Pastorino, Ugo, Skaug, Vidar, Haugen, Aage, Taioli, Emanuela, and Dragani, Tommaso A.
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- 2009
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18. Early Response Evaluation in Malignant Pleural Mesothelioma by Positron Emission Tomography With [18F]Fluorodeoxyglucose
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Ceresoli, Giovanni L., Chiti, Arturo, Zucali, Paolo A., Rodari, Marcello, Lutman, Romano F., Salamina, Silvia, Incarbone, Matteo, Alloisio, Marco, and Santoro, Armando
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- 2006
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19. A V141L polymorphism of the human LRMP gene is associated with survival of lung cancer patients
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Manenti, Giacomo, Galbiati, Federica, Pettinicchio, Angela, Spinola, Monica, Piconese, Silvia, Leoni, Vera Piera, Conti, Barbara, Ravagnani, Fernando, Incarbone, Matteo, Pastorino, Ugo, and Dragani, Tommaso A.
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- 2006
20. To Do Is Better: Prompt Surgery Is Indicated in COVID-19 Patients With Complicated Pneumatocele
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Castiglioni, Massimo, Pelosi, Giuseppe, and Incarbone, Matteo
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- 2022
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21. Read-through transcripts in lung: germline genetic regulation and correlation with the expression of other genes.
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Maspero, Davide, Dassano, Alice, Pintarelli, Giulia, Noci, Sara, Cecco, Loris De, Incarbone, Matteo, Tosi, Davide, Santambrogio, Luigi, Dragani, Tommaso A, and Colombo, Francesca
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GENETIC correlations ,GENETIC regulation ,FALSE discovery rate ,LUNGS - Abstract
Transcripts originating from the transcriptional read through of two adjacent, similarly oriented genes have been identified in normal and neoplastic tissues, but their functional role and the mechanisms that regulate their expression are mostly unknown. Here, we investigated whether the expression of read-through transcripts previously identified in the non-involved lung tissue of lung adenocarcinoma patients was genetically regulated. Data on genome-wide single nucleotide variant genotypes and expression levels of 10 read-through transcripts in 201 samples of lung tissue were combined to identify expression quantitative trait loci (eQTLs). Then, to identify genes whose expression levels correlated with the 10 read-through transcripts, we used whole transcriptome profiles available for 154 patients. For 8 read-though transcripts, we identified 60 eQTLs (false discovery rate <0.05), including 17 cis -eQTLs and 43 trans -eQTLs. These eQTLs did not maintain their behavior on the 'parental' genes involved in the read-through transcriptional event. The expression levels of 7 read-through transcripts were found to correlate with the expression of other genes: CHIA–PIFO and CTSC–RAB38 correlated with CHIA and RAB38 , respectively, while 5 other read-through transcripts correlated with 43 unique non-parental transcripts; thus offering indications about the molecular processes in which these chimeric transcripts may be involved. We confirmed 9 eQTLs (for 4 transcripts) in the non-involved lung tissue from an independent series of 188 lung adenocarcinoma patients. Therefore, this study indicates that the expression of four read-through transcripts in normal lung tissue is under germline genetic regulation, and that this regulation is independent of that of the genes involved in the read-through event. [ABSTRACT FROM AUTHOR]
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- 2020
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22. Surgical Resections of Superinfected Pneumatoceles in a COVID-19 Patient.
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Castiglioni, Massimo, Pelosi, Giuseppe, Meroni, Alberto, Tagliabue, Marta, Uslenghi, Elisabetta, Salaris, Davide, and Incarbone, Matteo
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Emerging studies on radiologic findings in patients with coronavirus disease 2019 (COVID-19) report a high incidence of bilateral lung involvement, with ground-glass opacities imaging being the most common pattern on computed tomography. Cystic lesions, such as pneumatoceles, are rare, although they may occur in 10% of cases. Cyst formation may be explained by a focal pulmonary trauma caused by mechanical ventilation or infection-related damage to the alveolar walls leading to pneumatoceles. The superinfection of pneumatoceles is a potential life-threatening condition for which no standardized therapeutic algorithm has been accepted. We report a case of a COVID-19 patient successfully treated by lung resections for infected pneumatoceles. [ABSTRACT FROM AUTHOR]
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- 2021
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23. IGF-1R and p-AKT expression in 132 resected thymomas and thymic carcinomas
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Zucali, Paolo A., Petrini, Iacopo, Lorenzi, Elena, Merino, Maria, Cao, Liang, Di Tommaso, Luca, Lee, Hye Seung, Incarbone, Matteo, Walter, Beatriz A, Simonelli, Matteo, Roncalli, Massimo, Santoro, Armando, and Giaccone, Giuseppe
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Adult ,Aged, 80 and over ,Male ,Thymoma ,Thymus Neoplasms ,Middle Aged ,Prognosis ,Article ,Receptor, IGF Type 1 ,Oncogene Protein v-akt ,Treatment Outcome ,Serine ,Humans ,Female ,Phosphorylation ,Aged - Abstract
Thymic malignancies are rare tumors. The insulin-like growth factor-1 (IGF-1)/IGF-1 receptor (IGF-1R) system is involved in the development of the thymus. IGF-1R expression in thymic epithelial malignancies is unknown.The authors investigated the expression of IGF-1R and phosphorylated AKT serine 473 (p-AKT) by using immunohistochemistry and examined the clinicopathologic correlations in a retrospective, single-institution surgical series of 132 patients with thymic epithelial malignancies.Earlier disease stage, less aggressive histologic types, and complete resection were significant positive prognostic factors for disease-related survival and progression-free survival, and being a woman was a better prognostic factor for disease-related survival. IGF-1R and p-AKT protein levels were expressed in 20% and 36% of thymic tumors, respectively. Both markers were expressed more commonly in recurrent disease than in primary tumors, in more aggressive subtypes, and in more advanced disease stages. There was a trend toward better survival and progression-free survival in patients who were negative for IGF-1R or p-AKT expression in the whole series. When only the 91 primary tumors, IGF1R expression was associated with worse progression-free survival (P.001).The current retrospective analysis demonstrated that disease stage, tumor histology, sex, and resection type were major prognostic factors in the survival of patients with thymic malignancies. The expression levels of IGF-1R and p-AKT in thymic tumors suggested that IGF-1R is a potential target for treatment.
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- 2010
24. Human Lung Tissue Transcriptome: Influence of Sex and Age.
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Dugo, Matteo, Cotroneo, Chiara E., Lavoie-Charland, Emilie, Incarbone, Matteo, Santambrogio, Luigi, Rosso, Lorenzo, van den Berge, Maarten, Nickle, David, Paré, Peter D., Bossé, Yohan, Dragani, Tommaso A., and Colombo, Francesca
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HUMAN life cycle ,LUNG physiology ,GENE expression ,ADENOCARCINOMA ,X chromosome ,PATIENTS - Abstract
Background: Sex and age strongly influence the pathophysiology of human lungs, but scarce information is available about their effects on pulmonary gene expression. Methods: We followed a discovery-validation strategy to identify sex- and age-related transcriptional differences in lung. Results: We identified transcriptional profiles significantly associated with sex (215 genes; FDR < 0.05) and age at surgery (217 genes) in non-involved lung tissue resected from 284 lung adenocarcinoma patients. When these profiles were tested in three independent series of non-tumor lung tissue from an additional 1,111 patients, we validated the association with sex and age for 25 and 22 genes, respectively. Among the 17 sex-biased genes mapping on chromosome X, 16 have been reported to escape X-chromosome inactivation in other tissues or cells, suggesting that this mechanism influences lung transcription too. Our 22 age-related genes partially overlap with genes modulated by age in other tissues, suggesting that the aging process has similar consequences on gene expression in different organs. Finally, seven genes whose expression was modulated by sex in non-tumor lung tissue, but no age-related gene, were also validated using publicly available data from 990 lung adenocarcinoma samples, suggesting that the physiological regulatory mechanisms are only partially active in neoplastic tissue. Conclusions: Gene expression in non-tumor lung tissue is modulated by both sex and age. These findings represent a validated starting point for research on the molecular mechanisms underlying the observed differences in the course of lung diseases among men and women of different ages. [ABSTRACT FROM AUTHOR]
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- 2016
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25. Primary pulmonary meningioma: Report of a case and review of the literature
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Incarbone, Matteo, Ceresoli, Giovanni Luca, Di Tommaso, Luca, Cappuzzo, Federico, Inzirillo, Francesco, Infante, Maurizio, and Alloisio, Marco
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- 2008
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26. A polygenic model with common variants may predict lung adenocarcinoma risk in humans.
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Galvan, Antonella, Falvella, Felicia S., Spinola, Monica, Frullanti, Elisa, Leoni, Vera P., Noci, Sara, Alonso, Maria R., Zolin, Anna, Spada, Elena, Milani, Silvano, Pastorino, Ugo, Incarbone, Matteo, Santambrogio, Luigi, Neira, Anna Gonzalez, and Dragani, Tommaso A.
- Abstract
Genome-wide screening for genetic loci associated with risk of lung adenocarcinoma (ADCA) was carried out in pooled DNA using the Illumina 300K single-nucleotide polymorphism (SNP) array, in a joint analysis of 2 Italian case-control series matched by age, gender and smoking habit. The rare allele carrier status of 8 SNPs was associated with a decreased lung ADCA risk [odds ratios (OR): 0.6-0.8]. In a polygenic model characterized by additive and interchangeable effects, individuals carrying 2 to 6 rare alleles at these 8 SNPs showed a significant trend toward a decreased risk of lung ADCA (up to OR of 0.3). These results suggest the relevance of a polygenic model in the modulation of individual risk of lung ADCA in the general population. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
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- 2008
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27. Prognostic value of loss of heterozygosity and KRAS2 mutations in lung adenocarcinoma.
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De Gregorio, Laura, Manenti, Giacomo, Incarbone, Matteo, Pilotti, Silvana, Pastorino, Ugo, Pierotti, Marco A., and Dragani, Tommaso A.
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- 1998
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28. Assessment of Mediastinal Involvement in Lung Cancer with Technetium-99m-Sestamibi SPECT.
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Chili, Arturo, Maffioli, Lorenzo S., Infante, Maurizio, Grasselli, Giacomo, Incarbone, Matteo, Gasparini, Massimo D., Savelli, Giordano, and Bombardieri, Emilio
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- 1996
29. Protection of right pneumonectomy bronchial sutures with a pedicled thymus flap.
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Infante, Maurizio V., Alloisio, Marco, Balzarini, Luca, Cariboni, Umberto, Testori, Alberto, Incarbone, Matteo A., Macri, Paolo, and Ravasi, Gianluigi
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PNEUMONECTOMY ,DRUG therapy ,RADIOTHERAPY ,ADULT respiratory distress syndrome - Abstract
A pedicled flap obtained by mobilizing the right lobe of the thymus was used to protect bronchial sutures in 29 consecutive patients undergoing a right pneumonectomy and in 4 additional patients. Fourteen patients had received preoperative chemotherapy with or without radiotherapy. The flap procedure was, in general, easy to do, required an average time of 20.4 minutes, and did not cause added operative morbidity. Postoperative magnetic resonance imaging, performed in 21 of the 29 patients who had pneumonectomy, showed a viable flap in every instance. One bronchopleural fistula occurred in a pneumonectomy patient after induction chemotherapy plus radiotherapy in a patient in the pneumonectomy group in whom adult respiratory distress syndrome developed postoperatively and who required prolonged mechanical ventilation. [Copyright &y& Elsevier]
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- 2004
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30. Linkage disequilibrium pattern in the L- myc gene in Italian and Japanese non-small-cell lung-cancer patients.
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Spinola, Monica, Nomoto, Tomoko, Manenti, Giacomo, Falvella, F. Stefania, Brega Massone, Pier Paolo, Conti, Barbara, Cataldo, Ignazio, Valagussa, Pinuccia, Incarbone, Matteo, Miyamoto, Kazuaki, Ushijima, Toshikazu, and Dragani, Tommaso A.
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- 2001
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31. Dante: A Randomised Trial on Early Diagnosis of Lung Cancer With Low-dose Spiral CT (LDCT); Initial Announcemen
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Infante, Maurizio V., Lutman, Fabio R., Cavuto, Silvio, Brambilla, Giorgio, Cariboni, Umberto, Alloisio, Marco, Testori, Alberto, Incarbone, Matteo, Roncalli, Massimo, and Ravasi, Gianluigi
- Published
- 2003
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32. Genetic susceptibility variants for lung cancer: replication study and assessment as expression quantitative trait loci.
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Pintarelli, Giulia, Cotroneo, Chiara Elisabetta, Noci, Sara, Dugo, Matteo, Galvan, Antonella, Delli Carpini, Simona, Citterio, Lorena, Manunta, Paolo, Incarbone, Matteo, Tosi, Davide, Santambrogio, Luigi, Dragani, Tommaso A., and Colombo, Francesca
- Abstract
Many single nucleotide polymorphisms (SNPs) have been associated with lung cancer but lack confirmation and functional characterization. We retested the association of 56 candidate SNPs with lung adenocarcinoma risk and overall survival in a cohort of 823 Italian patients and 779 healthy controls, and assessed their function as expression quantitative trait loci (eQTLs). In the replication study, eight SNPs (rs401681, rs3019885, rs732765, rs2568494, rs16969968, rs6495309, rs11634351, and rs4105144) associated with lung adenocarcinoma risk and three (rs9557635, rs4105144, and rs735482) associated with survival. Five of these SNPs acted as cis-eQTLs, being associated with the transcription of IREB2 (rs2568494, rs16969968, rs11634351, rs6495309), PSMA4 (rs6495309) and ERCC1 (rs735482), out of 10,821 genes analyzed in lung. For these three genes, we obtained experimental evidence of differential allelic expression in lung tissue, pointing to the existence of in-cis genomic variants that regulate their transcription. These results suggest that these SNPs exert their effects on cancer risk/outcome through the modulation of mRNA levels of their target genes. [ABSTRACT FROM AUTHOR]
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- 2017
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33. Morphological convergence characterizes the evolution of Xanthophyceae (Heterokontophyta): evidence from nuclear SSU rDNA and plastidial rbcL genes
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Negrisolo, Enrico, Maistro, Silvia, Incarbone, Matteo, Moro, Isabella, Dalla Valle, Luisa, Broady, Paul A., and Andreoli, Carlo
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XANTHOPHYCEAE , *GENES , *PHYCOLOGY , *TRIBONEMATALES - Abstract
Xanthophyceae are a group of heterokontophyte algae. Few molecular studies have investigated the evolutionary history and phylogenetic relationships of this class. We sequenced the nuclear-encoded SSU rDNA and chloroplast-encoded rbcL genes of several xanthophycean species from different orders, families, and genera. Neither SSU rDNA nor rbcL genes show intraspecific sequence variation and are good diagnostic markers for characterization of problematic species. New sequences, combined with those previously available, were used to create different multiple alignments. Analyses included sequences from 26 species of Xanthophyceae plus three Phaeothamniophyceae and two Phaeophyceae taxa used as outgroups. Phylogenetic analyses were performed according to Bayesian inference, maximum likelihood, and maximum parsimony methods. We explored effects produced on the phylogenetic outcomes by both taxon sampling as well as selected genes. Congruent results were obtained from analyses performed on single gene multiple alignments as well as on a data set including both SSU rDNA and rbcL sequences. Trees obtained in this study show that several currently recognized xanthophycean taxa do not form monophyletic groups. The order Mischococcales is paraphyletic, while Tribonematales and Botrydiales are polyphyletic even if evidence for the second order is not conclusive. Botrydiales and Vaucheriales, both including siphonous taxa, do not form a clade. The families Botrydiopsidaceae, Botryochloridaceae, and Pleurochloridaceae as well as the genera Botrydiopsis and Chlorellidium are polyphyletic. The Centritractaceae and the genus Bumilleriopsis also appear to be polyphyletic but their monophyly cannot be completely rejected with current evidence. Our results support morphological convergence at any taxonomic rank in the evolution of the Xanthophyceae. Finally, our phylogenetic analyses exclude an origin of the Xanthophyceae from a Vaucheria-like ancestor and favor a single early origin of the coccoid cell form. [Copyright &y& Elsevier]
- Published
- 2004
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34. Spread of hyperplastic pulmonary neuroendocrine cells into air spaces (S.H.I.P.M.E.N.T.S): A proof for artifact.
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Pelosi, Giuseppe, Nesa, Francesco, Taietti, Davide, Servillo, Sascia Pietro, Papanikolaou, Nikolaos, Zompatori, Maurizio, Meroni, Alberto, Harari, Sergio, and Incarbone, Matteo
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NEUROENDOCRINE cells , *CARCINOID , *AIR , *LUNG cancer , *EVIDENCE , *SPACE - Abstract
• Spread through air spaces is suggested to be invasion way of lung parenchyma. • Spread through air spaces has been described around lung neuroendocrine neoplasms. • Spread through air spaces may be made up by hyperplastic neuroendocrine cells. • Spread through air spaces is likely to be an ex vivo artifact due to tissue manipulation. Spread through air spaces (STAS) is a recently proposed invasion way of lung cancer, including neuroendocrine (NE) neoplasms. However, if this phenomenon is a real one or an artifact while manipulating lung specimens, it is still matter of debate. Three consecutive patients with newly diagnosed diffuse idiopathic pulmonary NE cell hyperplasia (DIPNECH) were reviewed for STAS. In well-fixed lung specimens, DIPNECH was seen to coexist with atypical carcinoid, bifocal typical carcinoid and adenocarcinoma in the three patients, respectively. While STAS was not observed at the growing edges of tumors, a few freely-floating aggregates of hyperplastic NE cells within air spaces were noticed to emanate from foci of NE hyperplasia and tumorlets and in intimate association with normal bronchiolar cells and erythrocytes to denote artifactual derivation upon tissue manipulation. Traveling of hyperplastic NE cells through air spaces is likely to artifactually occur via knife, surgeon or other way, thus challenging invasion by STAS. [ABSTRACT FROM AUTHOR]
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- 2019
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35. Metastatic mucinous ovarian carcinoma simulating lung primary: an integrated diagnostic lesson.
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Pelosi G, De Luca M, Cannone M, Balladore E, Ricotti I, Toniolo D, and Incarbone M
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- Female, Humans, Diagnosis, Differential, Carcinoma, Ovarian Epithelial diagnosis, Lung pathology, Ovarian Neoplasms diagnosis, Ovarian Neoplasms pathology, Adenocarcinoma, Mucinous diagnosis, Adenocarcinoma, Mucinous pathology
- Abstract
We herein document a rare instance of primary mucinous ovarian carcinoma metastatic to the left lung, whose deceptive secondary derivation was already envisaged according to the spectacular thromboembolism involving small pulmonary vessels, thereby realizing a centrifugal and centripetal metastatizing loop. This presentation was indicative of dismal prognosis. A multimodal biomarker key approach is herein emphasized, which included close clinico-pathologic data integration., (Copyright © 2022 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)
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- 2022
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36. Programmed death ligand 1 expression in early stage, resectable non-small cell lung cancer.
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D'Arcangelo M, D'Incecco A, Ligorio C, Damiani S, Puccetti M, Bravaccini S, Terracciano L, Bennati C, Minuti G, Vecchiarelli S, Landi L, Milesi M, Meroni A, Ravaioli S, Tumedei MM, Incarbone M, and Cappuzzo F
- Abstract
Introduction: For several years non-small cell lung cancer (NSCLC) has been considered non-immunogenic. Recent advances in antitumor immunity brought to the discovery of checkpoints that modulate immune response against cancer. One of them is programmed death receptor 1 (PD-1) and its ligand (PD-L1). Although PD-L1 expression seems predictive of response to anti-PD-1/PD-L1 agents, its prognostic value is unclear. In this study we investigated the prognostic value of PD-L1 expression and its correlation with clinical-pathological characteristics in a cohort of surgically resected NSCLC., Material and Methods: PD-L1 expression was evaluated in 289 surgically resected NSCLC samples by immunohistochemistry. Our cohort included patients not exposed to adjuvant chemotherapy. PD-L1 status was defined as: 1) PD-L1 high (tumor proportion score, TPS≥50%), PD-L1 low (TPS 1-49%), PD-L1 negative (TPS<1%); 2) PD-L1 positive (TPS≥50%) and negative (TPS<50%); 3) as a continuous variable., Results: Patients were mostly males (79%), former or current smokers (81%), with a median age of 67 years, non-squamous histology (67.5%) and high-grade tumors (55%). PD-L1 tumors were 18.7%. There was no significant association with sex, age, smoking status and histology. A strong correlation between high PD-L1 expression and tumor grade was detected. The difference in median OS in the different groups of patients was not statistically significant., Conclusion: PD-L1 is not prognostic in surgically resected NSCLC. The association with tumor differentiation suggests that grading could represent an easy-to-assess tool for selecting subjects potentially sensitive to immunotherapy warranting further investigations., Competing Interests: CONFLICTS OF INTEREST Dr Federico Cappuzzo: consultancy and advisory boards for Roche, Astrazeneca, BMS, MSD, Pfizer.
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- 2019
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37. Read-through transcripts in normal human lung parenchyma are down-regulated in lung adenocarcinoma.
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Pintarelli G, Dassano A, Cotroneo CE, Galvan A, Noci S, Piazza R, Pirola A, Spinelli R, Incarbone M, Palleschi A, Rosso L, Santambrogio L, Dragani TA, and Colombo F
- Subjects
- Adenocarcinoma pathology, Adenocarcinoma surgery, Adenocarcinoma of Lung, Aged, DNA, Complementary genetics, Down-Regulation, Female, Gene Expression Profiling, High-Throughput Nucleotide Sequencing, Humans, Lung Neoplasms pathology, Lung Neoplasms surgery, Male, Middle Aged, Pneumonectomy, RNA genetics, Real-Time Polymerase Chain Reaction, Sequence Analysis, RNA, Adenocarcinoma genetics, Lung pathology, Lung Neoplasms genetics, Mutant Chimeric Proteins genetics, RNA Splicing, Tumor Suppressor Proteins genetics
- Abstract
Read-through transcripts result from the continuous transcription of adjacent, similarly oriented genes, with the splicing out of the intergenic region. They have been found in several neoplastic and normal tissues, but their pathophysiological significance is unclear. We used high-throughput sequencing of cDNA fragments (RNA-Seq) to identify read-through transcripts in the non-involved lung tissue of 64 surgically treated lung adenocarcinoma patients. A total of 52 distinct read-through species was identified, with 24 patients having at least one read-through event, up to a maximum of 17 such transcripts in one patient. Sanger sequencing validated 28 of these transcripts and identified an additional 15, for a total of 43 distinct read-through events involving 35 gene pairs. Expression levels of 10 validated read-through transcripts were measured by quantitative PCR in pairs of matched non-involved lung tissue and lung adenocarcinoma tissue from 45 patients. Higher expression levels were observed in normal lung tissue than in the tumor counterpart, with median relative quantification ratios between normal and tumor varying from 1.90 to 7.78; the difference was statistically significant (P < 0.001, Wilcoxon's signed-rank test for paired samples) for eight transcripts: ELAVL1-TIMM44, FAM162B-ZUFSP, IFNAR2-IL10RB, INMT-FAM188B, KIAA1841-C2orf74, NFATC3-PLA2G15, SIRPB1-SIRPD, and SHANK3-ACR. This report documents the presence of read-through transcripts in apparently normal lung tissue, with inter-individual differences in patterns and abundance. It also shows their down-regulation in tumors, suggesting that these chimeric transcripts may function as tumor suppressors in lung tissue., Competing Interests: The authors declare no conflicts of interest.
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- 2016
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38. Identifying and targeting ROS1 gene fusions in non-small cell lung cancer.
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Davies KD, Le AT, Theodoro MF, Skokan MC, Aisner DL, Berge EM, Terracciano LM, Cappuzzo F, Incarbone M, Roncalli M, Alloisio M, Santoro A, Camidge DR, Varella-Garcia M, and Doebele RC
- Subjects
- Adult, Aged, Antigens, Differentiation, B-Lymphocyte genetics, Cell Cycle drug effects, Cell Cycle genetics, Cell Proliferation drug effects, Crizotinib, Female, Histocompatibility Antigens Class II genetics, Humans, Male, Middle Aged, Neoplasm Staging, Protein Kinase Inhibitors administration & dosage, Pyrazoles administration & dosage, Pyridines administration & dosage, Syndecan-4 genetics, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung metabolism, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung therapy, Oncogene Proteins, Fusion genetics, Oncogene Proteins, Fusion metabolism, Protein-Tyrosine Kinases antagonists & inhibitors, Protein-Tyrosine Kinases genetics, Protein-Tyrosine Kinases metabolism, Proto-Oncogene Proteins antagonists & inhibitors, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins metabolism, Sodium-Phosphate Cotransporter Proteins, Type IIb genetics, Sodium-Phosphate Cotransporter Proteins, Type IIb metabolism
- Abstract
Purpose: Oncogenic gene fusions involving the 3' region of ROS1 kinase have been identified in various human cancers. In this study, we sought to characterize ROS1 fusion genes in non-small cell lung cancer (NSCLC) and establish the fusion proteins as drug targets., Experimental Design: An NSCLC tissue microarray (TMA) panel containing 447 samples was screened for ROS1 rearrangement by FISH. This assay was also used to screen patients with NSCLC. In positive samples, the identity of the fusion partner was determined through inverse PCR and reverse transcriptase PCR. In addition, the clinical efficacy of ROS1 inhibition was assessed by treating a ROS1-positive patient with crizotinib. The HCC78 cell line, which expresses the SLC34A2-ROS1 fusion, was treated with kinase inhibitors that have activity against ROS1. The effects of ROS1 inhibition on proliferation, cell-cycle progression, and cell signaling pathways were analyzed by MTS assay, flow cytometry, and Western blotting., Results: In the TMA panel, 5 of 428 (1.2%) evaluable samples were found to be positive for ROS1 rearrangement. In addition, 1 of 48 patients tested positive for rearrangement, and this patient showed tumor shrinkage upon treatment with crizotinib. The patient and one TMA sample displayed expression of the recently identified SDC4-ROS1 fusion, whereas two TMA samples expressed the CD74-ROS1 fusion and two others expressed the SLC34A2-ROS1 fusion. In HCC78 cells, treatment with ROS1 inhibitors was antiproliferative and downregulated signaling pathways that are critical for growth and survival., Conclusions: ROS1 inhibition may be an effective treatment strategy for the subset of patients with NSCLC whose tumors express ROS1 fusion genes., (©2012 AACR.)
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- 2012
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39. Multiple genetic loci modulate lung adenocarcinoma clinical staging.
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Frullanti E, Galvan A, Falvella FS, Manenti G, Colombo F, Vannelli A, Incarbone M, Alloisio M, Nosotti M, Santambrogio L, Gonzalez-Neira A, Pastorino U, and Dragani TA
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- Adenocarcinoma pathology, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor genetics, Female, Genetic Loci genetics, Humans, Kaplan-Meier Estimate, Linkage Disequilibrium, Lung Neoplasms pathology, Male, Middle Aged, Neoplasm Staging statistics & numerical data, Polymorphism, Single Nucleotide, Proportional Hazards Models, Young Adult, Adenocarcinoma genetics, Genome-Wide Association Study methods, Lung Neoplasms genetics, Neoplasm Staging methods
- Abstract
Purpose: The main prognostic factor of lung cancer patient outcome is clinical stage, a parameter of tumor aggressiveness. Our study was conducted to test whether germ line variations modulate individual differences in clinical stage., Experimental Design: We conducted a case-only genome-wide association study (GWAS) using a 620,901 single-nucleotide polymorphism (SNP) array in a first series of 600 lung adenocarcinoma (ADCA) patients and in a replication series of 317 lung ADCA patients., Results: GWAS identified 54 putatively associated SNPs, 3 of which were confirmed in the replication series. Joint analysis of the two series pointed to 22 statistically associated (P < 0.01) genetic variants that together explained about 20% of the phenotypic variation in clinical staging (P < 2 × 10(-16)) and showed a statistically significant difference in overall survival (P = 8.0 × 10(-8)). The strongest statistical association was observed at rs10278557 (P = 1.1 × 10(-5)), located in the mesenchyme homeobox 2 (MEOX2) gene., Conclusion: These data point to the role of germ line variations involving multiple loci in modulating clinical stage and, therefore, prognosis in lung ADCA patients., (©2011 AACR.)
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- 2011
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40. Increased MET gene copy number negatively affects survival of surgically resected non-small-cell lung cancer patients.
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Cappuzzo F, Marchetti A, Skokan M, Rossi E, Gajapathy S, Felicioni L, Del Grammastro M, Sciarrotta MG, Buttitta F, Incarbone M, Toschi L, Finocchiaro G, Destro A, Terracciano L, Roncalli M, Alloisio M, Santoro A, and Varella-Garcia M
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung mortality, Carcinoma, Non-Small-Cell Lung surgery, DNA Mutational Analysis, ErbB Receptors genetics, Female, Gene Dosage, Humans, In Situ Hybridization, Fluorescence, Kaplan-Meier Estimate, Lung Neoplasms mortality, Lung Neoplasms surgery, Male, Middle Aged, Prognosis, Proto-Oncogene Proteins c-met, Retrospective Studies, Tissue Array Analysis, Biomarkers, Tumor genetics, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms genetics, Proto-Oncogene Proteins genetics, Receptors, Growth Factor genetics
- Abstract
Purpose: To investigate the prognostic role of genomic gain for MET and epidermal growth factor receptor (EGFR) genes in surgically resected non-small-cell lung cancer (NSCLC)., Patients and Methods: This retrospective study included 447 NSCLC patients with available tumor tissue from primary lung tumor and survival data. EGFR and MET status was evaluated by fluorescent in situ hybridization (FISH) in tissue microarray sections., Results: EGFR FISH results were obtained in 376 cases. EGFR gene amplification and high polysomy (EGFR FISH+) were observed in 10.4% and 32.4% of cases, respectively. EGFR FISH-positive patients had a nonsignificant shorter survival than EGFR FISH-negative patients (P = .4). Activating EGFR mutations were detected in 9.7% of 144 stage I-II disease with no impact on survival. MET FISH analysis was performed in 435 cases. High MET gene copy number (mean > or = 5 copies/cell) was observed in 48 cases (MET+, 11.1%), including 18 cases with true gene amplification (4.1%). MET+ status was associated with advanced stage (P = .01), with grade 3 (P = .016) and with EGFR FISH+ result (P < .0001). No patient with activating EGFR mutation resulted MET+. In the whole population, MET-positive patients had shorter survival than MET-negative patients (P = .005). Multivariable model confirmed that MET-negative patients had a significant reduction in the risk of death than MET-positive patients (hazard ratio, 0.66; P = .04)., Conclusion: MET increased gene copy number is an independent negative prognostic factor in surgically resected NSCLC. EGFR gene gain does not impact survival after resection.
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- 2009
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41. Transcription deregulation at the 15q25 locus in association with lung adenocarcinoma risk.
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Falvella FS, Galvan A, Frullanti E, Spinola M, Calabrò E, Carbone A, Incarbone M, Santambrogio L, Pastorino U, and Dragani TA
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- Adenocarcinoma metabolism, Adenocarcinoma secondary, Adult, Aged, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell metabolism, Carcinoma, Squamous Cell secondary, Case-Control Studies, DNA genetics, DNA metabolism, Female, Genotype, Humans, Immunoenzyme Techniques, Iron Regulatory Protein 2 metabolism, Lung metabolism, Lung pathology, Lung Neoplasms metabolism, Lung Neoplasms pathology, Male, Middle Aged, Nerve Tissue Proteins metabolism, Polymerase Chain Reaction, Polymorphism, Single Nucleotide genetics, Proteasome Endopeptidase Complex metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Receptors, Nicotinic metabolism, Risk Factors, Adenocarcinoma genetics, Chromosomes, Human, Pair 15 genetics, Iron Regulatory Protein 2 genetics, Lung Neoplasms genetics, Nerve Tissue Proteins genetics, Proteasome Endopeptidase Complex genetics, Receptors, Nicotinic genetics
- Abstract
Purpose: We characterized the candidacy of the six candidate genes mapping in the chromosome 15q25 locus, which was previously reported as associated with lung cancer risk, and confirmed the locus association with lung cancer risk in an Italian population of lung adenocarcinoma patients and controls., Experimental Design: We did a quantitative analysis of mRNA levels of IREB2 (iron-responsive element-binding protein 2), LOC123688, PMSA4 [proteasome (prosome, macropain) subunit alpha type 4], CHRNB4 (cholinergic receptor nicotinic beta 4), CHRNA3 (cholinergic receptor nicotinic alpha 3), and CHRNA5 (cholinergic receptor nicotinic alpha 5) genes in paired normal lung and lung adenocarcinoma tissue, and an immunohistochemical localization of CHRNA3- and CHRNA5-encoded proteins. We also examined the association of CHRNA5 D398N polymorphism with lung cancer risk and with CHRNA5 mRNA levels in the normal lung., Results: Expression analysis of the six candidate genes mapping in the lung cancer risk-associated chromosome 15q25 locus revealed a 30-fold up-regulation of the gene encoding the CHRNA5 subunit and a 2-fold down-regulation of the CHRNA3 subunit in lung adenocarcinoma as compared with the normal lung. The expression of the four other candidate genes resulted either unchanged or absent. The carrier status of the 398N allele at the D398N polymorphism of the CHRNA5 gene was associated with lung adenocarcinoma risk (odds ratio, 1.5; 95% confidence interval, 1.2-2.0) in a population-based series of lung adenocarcinoma patients (n=467) and healthy controls (n=739). Analysis of a family-based series of nonsmoker lung cancer cases (n=80) and healthy sib controls (n=80) indicated a similar trend. In addition, the same D398N variation correlated with CHRNA5 mRNA levels in normal lung of adenocarcinoma patients., Conclusions: Our results point to the candidacy of the CHRNA5 gene for the 15q25 locus.
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- 2009
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42. Lack of telomerase activity in lung carcinoids is dependent on human telomerase reverse transcriptase transcription and alternative splicing and is associated with long telomeres.
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Zaffaroni N, Villa R, Pastorino U, Cirincione R, Incarbone M, Alloisio M, Curto M, Pilotti S, and Daidone MG
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- Carcinoid Tumor enzymology, Carcinoid Tumor genetics, DNA-Binding Proteins, Humans, Lung Neoplasms enzymology, Lung Neoplasms genetics, RNA, Messenger genetics, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, Telomerase metabolism, Telomere enzymology, Transcription, Genetic, Alternative Splicing, Carcinoid Tumor pathology, Lung Neoplasms pathology, Telomerase genetics, Telomere genetics
- Abstract
Purpose: Preliminary evidence indicates that telomerase activity is significantly less expressed in typical carcinoids than in large cell neuroendocrine carcinomas or in small cell lung cancers. Knowledge of the mechanisms by which telomerase is differentially regulated in neuroendocrine lung tumors is important for a better understanding of the pathogenesis of these malignancies., Experimental Design: We investigated telomerase activity in 86 neuroendocrine lung tumors and correlated the enzyme activity with the expression of the enzyme subunits [human RNA component (hTR), human telomerase reverse transcriptase (hTERT), and alternatively spliced hTERT variants], with the telomere-associated protein human protection of telomere-1, and with the telomere length pattern., Results: A significantly (P = 0.0001) lower frequency of telomerase-positive cases was found in typical carcinoids (14%) than in large cell neuroendocrine carcinomas (87%) and small cell lung cancers (92%). hTR was constitutively expressed in all carcinoids. Telomerase-negative carcinoids were characterized by the absence of any hTERT transcript, only displayed the beta(-) alternatively spliced variant, or concomitantly expressed the alpha(+)beta(+) full-length message with different combinations of alternatively spliced variants. However, in these tumors, a more abundant level of alternatively spliced transcripts than that of the alpha(+)beta(+) full-length transcript was generally found. No significant difference was observed in human protection of telomere-1 expression between telomerase-negative and telomerase-positive carcinoids. Telomeres were significantly (P < 0.05) longer in telomerase-negative carcinoids than in telomerase-positive carcinoids (median value, 9.15 versus 4.47 kb). However, alternative lengthening of telomeres, as shown by associated promyelocytic leukemia bodies, was not observed in these tumors., Conclusions: Our results indicate that telomerase is repressed in most lung carcinoids and that hTERT transcription and alternative splicing play a role in such a negative regulation. Moreover, the absence of any telomerase maintenance mechanism may contribute to the favorable prognosis of this malignancy.
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- 2005
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