Publications by authors named "Gianluigi Arrigoni"

31 Publications

Next Generation Sequencing in Non-Small Cell Lung Cancer: Pitfalls and Opportunities.

Diagnostics (Basel) 2020 Dec 15;10(12). Epub 2020 Dec 15.

Department of Oncology, IRCCS San Raffaele, 20132 Milan, Italy.

Lung cancer remains the first cause of cancer-related deaths worldwide. Thanks to the improvement in the knowledge of the biology of non-small cell lung cancer (NSCLC), patients' survival has significantly improved. A growing number of targetable molecular alterations have been identified. Next-generation sequencing (NGS) has become one of the methodologies entered in clinical practice and was recently recommended by the European society for medical oncology (ESMO) to perform a comprehensive molecular characterization in patients with cancer. The current review provides an overview of the clinical trials that have explored the impact of NGS in patients with cancer, its limits, and advantages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diagnostics10121092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765222PMC
December 2020

The impact of nodal status in major salivary gland carcinoma: A multicenter experience and proposal of a novel N-classification.

Oral Oncol 2021 Jan 30;112:105076. Epub 2020 Oct 30.

Section of Otorhinolaryngology - Head and Neck Surgery, Department of Neurosciences, University of Padua, Padua, Italy.

Objectives: Despite differences in oncological behavior, the 8th edition of AJCC TNM staging currently proposes the same N-classification for major salivary glands (MSG) carcinoma and squamous cell carcinoma of the upper aerodigestive tract. The present study aims to investigate a more reliable definition of N-categories for MSG carcinoma.

Materials And Methods: A retrospective multicenter study was performed, including 307 patients treated for primary MSG carcinoma from 1995 to 2019. Outcome measures included overall survival (OS), disease specific survival, and local, regional, and distant recurrence. Survival analysis was performed using log-rank test and Cox proportional-hazards model. Overall number (ON) and largest diameter (LD) of nodal metastases, including intra-parotid metastases, were considered to develop three novel proposals of N-classification; their performance were compared with the current TNM staging using Akaike information criterion (AIC), Bayesian information criterion (BIC), and Nagelkerke pseudo-R.

Results: Intra-parotid nodes, ON and LD of nodal metastases emerged as major prognosticators for OS, while extra-nodal extension did not impact on any survival. The current N-classification did not show a satisfactory OS stratification. Three novel N-classifications were developed according to number of metastatic nodes (0 vs 1-3 vs ≥ 4) and/or their maximum diameter (<20 mm vs ≥ 20 mm). They all showed better accuracy in OS stratification, and achieved better AIC, BIC and Nagelkerke pseudo-R indices when compared to current N-classification.

Conclusion: All the proposed N-classifications improved OS stratification and could help in defining a specific N-classification for MSG carcinoma. Their validation and assessment in an external cohort is needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.oraloncology.2020.105076DOI Listing
January 2021

Uncommon Site of Metastasis and Prolonged Survival in Patients with Anaplastic Thyroid Carcinoma: A Systematic Review of the Literature.

Cancers (Basel) 2020 Sep 10;12(9). Epub 2020 Sep 10.

Department of Otorhinolaryngology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.

Anaplastic thyroid carcinoma (ATC) is a very rare, highly aggressive malignant thyroid tumor with an overall survival from 3 to 5 months in most of the cases. Even the modern and intensive treatments seem not to be enough to provide a cure, also for the resectable ones, and the role of chemotherapy is still unclear but does not seem to prolong survival. Nevertheless, some patients survive longer and have a better outcome, even in the presence of metastasis, than what the literature reports. We present the case of a 64-year-old female affected by ATC, treated on February 2018 with surgery followed by chemoradiation. One year after surgery, the patient developed a subcutaneous recurrence that was radically resected and is still alive 29 months after the diagnosis. We propose a systematic review of the literature to deepen the knowledge of the prognostic factors of ATC with the aim to recognize and select the patients with a better outcome, even if metastatic, and to describe a very uncommon site of metastatization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12092585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564634PMC
September 2020

Prognostic role of positron emission tomography and computed tomography parameters in stage I lung adenocarcinoma.

Radiol Oncol 2020 05 28;54(3):278-284. Epub 2020 May 28.

Department of Thoracic Surgery, San Raffaele Hospital, Milan, Italy.

Background According to the current pathological classification, lung adenocarcinoma includes histological subtypes with significantly different prognoses, which may require specific surgical approaches. The aim of the study was to assess the role of CT and PET parameters in stratifying patients with stage I adenocarcinoma according to prognosis. Patients and methods Fifty-eight patients with pathological stage I lung adenocarcinoma who underwent surgical treatment were retrospectively reviewed. Adenocarcinoma in situ and minimally-invasive adenocarcinoma were grouped as non-invasive adenocarcinoma. Other histotypes were referred as invasive adenocarcinoma. CT scan assessed parameters were: ground glass opacity (GGO) ratio, tumour disappearance rate (TDR) and consolidation diameter. The prognostic role of the following PET parameters was also assessed: standardized uptake value (SUV) max, SUVindex (SUVmax to liver SUVratio), metabolic tumour volume (MTV), total lesion glycolysis (TLG). Results Seven patients had a non-invasive adenocarcinoma and 51 an invasive adenocarcinoma. Five-year disease-free survival (DFS) and cancer-specific survival (CSS) for non-invasive and invasive adenocarcinoma were 100% and 100%, 70% and 91%, respectively. Univariate analysis showed a significant difference in SUVmax, SUVindex, GGO ratio and TDR ratio values between non-invasive and invasive adenocarcinoma groups. Optimal SUVmax, SUVindex, GGO ratio and TDR cut-off ratios to predict invasive tumours were 2.6, 0.9, 40% and 56%, respectively. TLG, SUVmax, SUVindex significantly correlated with cancer specific survival. Conclusions CT and PET scan parameters may differentiate between non-invasive and invasive stage I adenocarcinomas. If these data are confirmed in larger series, surgical strategy may be selected on the basis of preoperative imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2478/raon-2020-0034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409601PMC
May 2020

Therapeutic strategy for tracheal chondrosarcoma: report of two cases.

Monaldi Arch Chest Dis 2020 Mar 12;90(1). Epub 2020 Mar 12.

Department of Thoracic Surgery, San Raffaele Hospital, Vita Salute San Raffaele University, Milan.

Primary chondrosarcoma of the trachea is an extremely rare tumor. We report two cases of tracheal chondrosarcoma describing the role of surgical and conservative treatment. Endoscopic treatment with rigid bronchoscopy was performed in both patients to restore airway patency and obtain histological specimens for diagnosis. One of the patients subsequently underwent successful tracheal resection and reconstruction. The other patient, who had a contraindication to surgical treatment due to associated diseases underwent iterative endoscopic LASER treatment and is alive three years after the first diagnosis. Surgical treatment remains the treatment of choice of tracheal chondrosarcoma. When surgery is contraindicated endoscopic treatment may allow relatively longterm survival due to the slow growth of these tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4081/monaldi.2020.1223DOI Listing
March 2020

Deconstructing IgG4-related disease involvement of midline structures: Comparison to common mimickers.

Mod Rheumatol 2017 Jul 13;27(4):638-645. Epub 2016 Sep 13.

a Unit of Medicine and Clinical Immunology, Ospedale San Raffaele , Milan , Italy.

Objective: A series of destructive and tumefactive lesions of the midline structures have been recently added to the spectrum of IgG4-related disease (IgG4-RD). We examined the clinical, serological, endoscopic, radiological, and histological features that might be of utility in distinguishing IgG4-RD from other forms of inflammatory conditions with the potential to involve the sinonasal area and the oral cavity.

Methods: We studied 11 consecutive patients with erosive and/or tumefactive lesions of the midline structures referred to our tertiary care center. All patients underwent serum IgG4 measurement, flow cytometry for circulating plasmablast counts, nasal endoscopy, radiological studies, and histological evaluation of tissue specimens. The histological studies included immunostaining studies to assess the number of IgG4 + plasma cells/HPF for calculation of the IgG4+/IgG + plasma cell ratio.

Results: Five patients with granulomatosis with polyangiitis (GPA), three with cocaine-induced midline destructive lesions (CIMDL), and three with IgG4-RD were studied. We found no clinical, endoscopic, or radiological findings specific for IgG4-RD. Increased serum IgG4 and plasmablasts levels were not specific for IgG4-RD. Rather, all 11 patients had elevated blood plasmablast concentrations, and several patients with GPA and CIMDL had elevated serum IgG4 levels. Storiform fibrosis and an IgG4+/IgG + plasma cell ratio >20% on histological examination, however, were observed only in patients with IgG4-RD.

Conclusions: Histological examination of bioptic samples from the sinonasal area and oral cavity represents the mainstay for the diagnosis of IgG4-RD involvement of the midline structures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14397595.2016.1227026DOI Listing
July 2017

Rapid targeted somatic mutation analysis of solid tumors in routine clinical diagnostics.

Oncotarget 2015 Oct;6(31):30592-603

Unit of Pathology, IRCCS San Raffaele Scientific Institute, Milano, Italy.

Tumor genotyping is an essential step in routine clinical practice and pathology laboratories face a major challenge in being able to provide rapid, sensitive and updated molecular tests. We developed a novel mass spectrometry multiplexed genotyping platform named PentaPanel to concurrently assess single nucleotide polymorphisms in 56 hotspots of the 5 most clinically relevant cancer genes, KRAS, NRAS, BRAF, EGFR and PIK3CA for a total of 221 detectable mutations. To both evaluate and validate the PentaPanel performance, we investigated 1025 tumor specimens of 6 different cancer types (carcinomas of colon, lung, breast, pancreas, and biliary tract, and melanomas), systematically addressing sensitivity, specificity, and reproducibility of our platform. Sanger sequencing was also performed for all the study samples. Our data showed that PentaPanel is a high throughput and robust tool, allowing genotyping for targeted therapy selection of 10 patients in the same run, with a practical turnaround time of 2 working days. Importantly, it was successfully used to interrogate different DNAs isolated from routinely processed specimens (formalin-fixed paraffin embedded, frozen, and cytological samples), covering all the requirements of clinical tests. In conclusion, the PentaPanel platform can provide an immediate, accurate and cost effective multiplex approach for clinically relevant gene mutation analysis in many solid tumors and its utility across many diseases can be particularly relevant in multiple clinical trials, including the new basket trial approach, aiming to identify appropriate targeted drug combination strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.5190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741554PMC
October 2015

KIT, PDGFRA, and BRAF mutational spectrum impacts on the natural history of imatinib-naive localized GIST: a population-based study.

Am J Surg Pathol 2015 Jul;39(7):922-30

*Department of Pathology and Molecular Genetics, Treviso General Hospital, Treviso †Experimental Oncology I, CRO Aviano National Cancer Institute, Aviano ‡Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale Tumori **Department of Pathology, IRCCS San Raffaele Hospital, Milano §Department of Pathology, Firenze University School of Medicine, Firenze ∥Department of Pathology, University of Marche, Ancona School of Medicine, Ancona ¶Department of Pathology, General Hospital, Bolzano #Department of Pathology, Macchi Foundation, Varese ††Department of Pathology, General Hospital, Bergamo ‡‡Department of Pathology, Perugia University, School of Medicine, Perugia §§Novartis Farma, Origgio Departments of ∥∥Surgery ¶¶Cancer Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy.

The mutation status of KIT or PDGFRA notoriously affects the response of advanced gastrointestinal stromal tumors (GISTs) to tyrosine kinase inhibitors. Conversely, it is currently still unclear whether mutation status impinges on the prognosis of localized, untreated GISTs. Hence, at present, this variable is not included in decision making for adjuvant therapy. A series of 451 primary localized GISTs were analyzed for KIT, PDGFRA, and BRAF mutations. Univariable and multivariable analyses and a backward selection procedure were used to assess the impact of mutation status on overall survival and to identify prognostically homogenous groups. Mutation was a significant prognostic indicator of overall survival in naive, localized GISTs (P<0.001): KIT-mutated patients had a worse outcome than PDGFRA-mutated or triple-negative (KIT, PDGFRA, BRAF wild-type) cases. Multivariable Cox regression models allowed us to identify 3 molecular risk groups: group I exhibited the best outcome and included PDGFRA exon 12, BRAF, and KIT exon 13-mutated cases; group II, of intermediate clinical phenotype (HR=3.06), included triple-negative, KIT exon 17, PDGFRA exon 18 D842V, and PDGFRA exon 14-mutated cases; group III displayed the worst outcome (hazard ratio=4.52), and comprised KIT exon 9 and exon 11 and PDGFRA exon 18 mutations apart from D842V. This study highlights the prognostic impact of mutation status on the natural course of GIST and suggests that the molecular prognostic grouping may complement the conventional clinicopathologic risk stratification criteria in decision making for adjuvant therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PAS.0000000000000418DOI Listing
July 2015

Ewing sarcoma of the small bowel: a study of seven cases, including one with the uncommonly reported EWSR1-FEV translocation.

Histopathology 2014 Jun 25;64(7):1014-26. Epub 2014 Feb 25.

Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.

Aims: Primary Ewing sarcoma of the ileum has rarely been documented. Little is known about its pathogenesis and clinical implications, and it would be helpful to identify novel molecular markers. EWSR1-FEV translocation is exceedingly rare in Ewing sarcoma, as FEV expression is restricted to prostate, brain and serotonin neuroendocrine cells (NE) and related tumours.

Methods And Results: Paraffin sections or snap-frozen material were used in this investigation. Tumours were investigated by means of immunohistochemistry, RT-PCR (EWSR1-FLI1, EWSR1-ERG and EWSR1-FEV transcripts), FISH analysis (EWSR1 break-apart and specific EWSR1-FEV translocation) and spectral karyotyping (SKY). Ten ileal neuroendocrine tumours (INET) made up the control group for EWSR1-FEV translocation. Among 445 Ewing sarcomas cases spanning a period of 20 years, seven (1.6%) arose in the ileum. All tumours were immunoreactive for synaptophysin, CD99, FLI1 and vimentin. FISH identified EWSR1 rearrangement in all cases, with EWSR1-FLI1 transcripts being detected in all but one tumour showing the uncommon EWSR1-FEV rearrangement, with SKY, RT-PCR and FISH confirmation. The mean survival of EWSR1-FLI1 patients was 14 months, whereas the EWSR1-FEV patient was alive after 15 years despite several recurrences controlled by surgery alone. No INET showed EWSR1 translocation.

Conclusions: Most primary Ewing sarcomas of the ileum show the common EWSR1-FLI1 translocation, but EWSR1-FEV could be specific for tumours arising in the ileum and showing better prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/his.12350DOI Listing
June 2014

Neuroblastoma tumorigenesis is regulated through the Nm23-H1/h-Prune C-terminal interaction.

Sci Rep 2013 ;3:1351

Centro di Ingegneria Genetica e Biotecnologie Avanzate-CEINGE, Naples, Italy.

Nm23-H1 is one of the most interesting candidate genes for a relevant role in Neuroblastoma pathogenesis. H-Prune is the most characterized Nm23-H1 binding partner, and its overexpression has been shown in different human cancers. Our study focuses on the role of the Nm23-H1/h-Prune protein complex in Neuroblastoma. Using NMR spectroscopy, we performed a conformational analysis of the h-Prune C-terminal to identify the amino acids involved in the interaction with Nm23-H1. We developed a competitive permeable peptide (CPP) to impair the formation of the Nm23-H1/h-Prune complex and demonstrated that CPP causes impairment of cell motility, substantial impairment of tumor growth and metastases formation. Meta-analysis performed on three Neuroblastoma cohorts showed Nm23-H1 as the gene highly associated to Neuroblastoma aggressiveness. We also identified two other proteins (PTPRA and TRIM22) with expression levels significantly affected by CPP. These data suggest a new avenue for potential clinical application of CPP in Neuroblastoma treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep01351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3584926PMC
August 2013

Plasma cell granuloma of the thyroid gland: a challenging diagnostic problem.

Int J Surg Pathol 2012 Oct 16;20(5):500-6. Epub 2011 Dec 16.

San Raffaele Scientific Institute, Milan, Italy.

This study reports a case of plasma cell granuloma of the thyroid gland in a 47-year-old woman, presenting with a right subhyoid mass and a previous diagnosis of Hashimoto thyroiditis dating back to 1988, which was made on a subtotal thyroidectomy. Plasma cell granuloma preferentially involves the lung, with only 18 cases of thyroid gland involvement having been reported to date in the English literature. Thyroid plasma cell granuloma preferentially affects women and classically shows a prominent plasma cell infiltrate embedded in a variable degree of fibrous stroma: only 2 of the reported cases exhibited the morphologic features of inflammatory myofibroblastic tumor. These morphologic features may raise problems in the differential diagnosis with other plasma cell-rich disorders, including infectious diseases and auto(dys)immune conditions, including the recently described "IgG4-related sclerosing disease." In view of these considerations, a contemporary diagnostic approach to thyroid plasma cell granuloma is therefore discussed here.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1066896911431453DOI Listing
October 2012

Natural history of imatinib-naive GISTs: a retrospective analysis of 929 cases with long-term follow-up and development of a survival nomogram based on mitotic index and size as continuous variables.

Am J Surg Pathol 2011 Nov;35(11):1646-56

Department of Pathology and Molecular Genetics, Treviso General Hospital, Italy.

Gastrointestinal stromal tumor (GIST) natural history per se has not been extensively investigated yet, with most data being drawn from large studies with a relevant referral bias. Hence, the estimation of prognosis still remains a critical issue. We retrospectively evaluated 929 GISTs resected between 1980 and 2000 in 35 Italian institutions. A total of 526 patients were found to be suitable for refining risk assessment through the development of a survival nomogram. Median follow-up was 126 months. On testing for potential prognostic parameters, age, tumor site, size, and mitotic index proved to be predictors of OS on both univariable and multivariable Cox model analyses, whereas necrosis and cytonuclear atypia were significant on univariable analysis only. The discriminative ability of the model, including the parameters selected after a backward procedure (C=0.72), improved compared with the National Institutes of Health 2002 (C=0.64) and the National Comprehensive Cancer Network 2007 (C=0.63). On the basis of these data we developed a prognostic nomogram for survival that considers site, size, and mitotic index as continuous variables, providing estimates stratified for patients aged ≤65 and >65 years. This nomogram is a tool based on survival. It overcomes problems that result from artificial categorization of continuous variables. We believe that in the future this should also be attempted by nomograms based on the risk of relapse.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PAS.0b013e31822d63a7DOI Listing
November 2011

Correlation of NM23-H1 cytoplasmic expression with metastatic stage in human prostate cancer tissue.

Naunyn Schmiedebergs Arch Pharmacol 2011 Oct 7;384(4-5):489-98. Epub 2011 May 7.

CEINGE, Via Gaetano Salvatore, 486, 80145, Naples, Italy.

Nm23-H1 has been identified as a metastatic suppressor gene in murine melanoma cell lines. Several functions have been attributed to its activity in cancer, including a histidine kinase activity, DNA repair, and regulation of other proteins involved in metastatic formation. While in breast cancer, NM23-H1 overexpression indicates a benign status through impairing progression of disease, its function is opposite in other cancers; e.g., neuroblastoma. To further understand this dichotomy of function in cancer, we have analyzed its function in prostate cancer, in which the relationship between NM23-H1 expression and prognostic state is today controversial. In vitro, overexpression of NM23-H1 in PC3 cells inhibited their cell motility, while downregulation of NM23-H1 expression in these cells by RNA interference showed enhanced cell motility. Immunohistochemistry analysis performed on 346 prostate cancer tissue samples showed a relationship between high levels of NM23-H1 expression in the nuclei of these tumorigenic cells and elevated Gleason score, with high levels of NM23-H1 cytoplasmic staining related to metastatic stage. This retrospective survival study demonstrates that high levels of NM23-H1 expression in the cytoplasm determine recurrence of prostate-specific antigen levels only in those patients with metastatic disease. Our findings suggest a correlation between high levels of NM23-H1 protein in the cytoplasm of the cells and progression of prostate cancer to metastasis, thus definitively identifying NM23-H1 as a new negative prognostic marker in prostate cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00210-011-0645-7DOI Listing
October 2011

Anti-IL-10R antibody improves the therapeutic efficacy of targeted liposomal oligonucleotides.

J Control Release 2009 Sep 7;138(2):122-7. Epub 2009 May 7.

Laboratory of Oncology, G. Gaslini Children's Hospital, 16147 Genoa, Italy.

High-risk Neuroblastoma (NB) has still a poor prognosis. Liposomes targeted to NB cells and encapsulating antisense CpG-containing oligonucleotides (TL-asCpG) had increased anti-tumour efficacy in NB xenografts compared to free asCpG. Interleukin 10 (IL-10) suppresses antigen presenting cell activation contributing to tumour-mediated immune suppression. In principle, combination of TL-asCpG and antibodies against IL-10 receptor (aIL-10R) could prolong immune system activation, leading to better therapeutic results. Mice treated with TL-asCpG 4 h after human NB cell inoculation survived significantly longer than controls. An increased life span was achieved also in mice receiving TL-asCpG 24 and 72 h after NB cell challenge. The addition of aIL-10R to TL-asCpG in the 4-h protocol significantly increased the percentage of long term survivors compared to TL-asCpG only. Surviving mice treated with the combined strategy were completely cured. In contrast, long term surviving mice treated only with TL-asCpG presented lymph node infiltration with NB cells. TL-asCpG plus aIL-10R treatment was significantly superior to TL-asCpG alone also for the 24-h protocol. Ex vivo experiments demonstrated that the combined therapy evoked a stronger and more prolonged immune system activation compared to monotherapy. These results support the feasibility of a clinical trial with TL-asCpG and aIL-10R in advanced NB patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jconrel.2009.05.006DOI Listing
September 2009

Pregnant woman presenting with a gross retroperitoneal mass: surgical treatment with caval replacement.

Eur Urol 2008 Sep 2;54(3):677-80. Epub 2008 Jul 2.

Department of Urology, Vita-Salute University San Raffaele, Milan, Italy.

A 40-year-old woman in the twenty-fifth week of pregnancy presented with a gross retroperitoneal mass. At the end of the pregnancy, the patient was submitted to surgery, and the gross infiltration of the inferior vena cava wall required the resection of the vena cava with its prosthetic substitution. The histopathological examination demonstrated the presence of a leiomyosarcoma of the inferior vena cava. An electronic video supplement showing the most important intraoperative passages is available online at doi:10.1016/j.eururo.2008.06.074.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eururo.2008.06.074DOI Listing
September 2008

Pleuropulmonary blastoma in the area of a diagnosed congenital lung cyst.

Ann Thorac Surg 2008 Feb;85(2):658-60

Department of Thoracic Surgery, University and Scientific Institute H San Raffaele, Milan, Italy.

Pleuropulmonary blastoma is a rare and aggressive neoplasm typically occurring in young children, even in newborns. Onset of the disease can be identified in the area of a previously diagnosed lung cyst. We report a case of a child previously diagnosed as having a right congenital lung cyst who had a pleuropulmonary blastoma developing in the same area. He underwent surgical resection of the neoplasm followed by chemotherapy. After 20 months he is alive and well.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.athoracsur.2007.08.012DOI Listing
February 2008

Localized organizing pneumonia: report of 21 cases.

Ann Thorac Surg 2007 Jun;83(6):1946-51

Department of Thoracic Surgery, San Raffaele Scientific Institute, Milan, Italy.

Background: Thoracic surgeons have limited experience with treating localized organizing pneumonia owing to its rare occurrence in routine clinical practice.

Methods: We retrospectively investigated the clinicopathologic features of 21 patients with localized organizing pneumonia observed between 2001 and 2004.

Results: There were 15 men and 6 women. Mean age was 63 years. Eight patients (38%) were symptomatic. Computed tomographic scan showed a single lesion in 17 patients (12 nodules and 5 masses) and bilateral lesions in 4. Wedge resection was performed in 16 patients and lobectomy in 5. There was no operative mortality. Follow-up was complete in all patients (range, 2 to 46 months; median, 20 months). Surgery was curative in 15 of 17 patients with a single lesion, and no recurrence was observed (p < 0.005). The remaining 2 patients with a single lesion (2 masses) had a local relapse with the appearance of nodular lesions in the residual parenchyma. Both these patients received steroids with resolution of the lesions. All 4 patients with bilateral lesions who underwent surgery for diagnostic purposes received steroids with improvement of the radiologic aspect in 3 and stabilization of the lesions in 1.

Conclusions: Clinical and radiologic findings of localized organizing pneumonia are nonspecific, and this unusual entity is difficult to differentiate from a primary or metastatic tumor. Surgical resection allows both diagnosis and cure. However, considering the benignity of the lesion and the efficacy of steroids, major pulmonary resections should be avoided.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.athoracsur.2007.01.062DOI Listing
June 2007

New transcription factors in diagnostic hematopathology.

Adv Anat Pathol 2007 Jan;14(1):25-35

Pathology Unit, Scientific Institute San Raffaele, Milano, Italy.

The transcription factors (TFs) that controls the intricate machinery of multistep differentiation and activation programs of the lymphoid system, represent a complex array of proteins, whose identification and function has only in part been completed. TFs are usually expressed during specific differentiation or activation cellular programs, making them interesting tools in diagnostic immunohistochemistry. In fact, the specificity of some of these TFs for lineage or activation/differentiation passages or their abnormal expression in specific disease entity, represents a feature that has been exploited in diagnostic/prognostic immunohistochemistry. Bcl-6 was the prototype of this class of markers. Currently, the expanding knowledge of the TFs involved in the differentiation programs and in the activation processes of T-lymphocyte and B-lymphocyte in normal and neoplastic conditions and the availability of antibodies able to efficiently recognize these TFs in histologic material, represent a powerful tool in diagnostic hematopathology. In this review we will consider the basic biologic aspects and the applications in hematopathology of some of the lymphocyte-related TFs, including Pax5/BSAB, MUM1/IRF4, BOB1, Oct-2, T-bet, and FOXP3. This field is rapidly evolving, as witnessed by the ongoing growing number of novel TFs with possible diagnostic applications appearing in the literature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PAP.0b013e31802f0495DOI Listing
January 2007

Solitary fibrous tumors of the pleura: Immunohistochemical analysis and evaluation of prognostic factors after surgical treatment.

J Surg Oncol 2006 Jul;94(1):40-4

Department of Thoracic Surgery, Vita-Salute San Raffaele University, Scientific Institute H San Raffaele, Milan, Italy.

Background And Objectives: Solitary fibrous tumors of the pleura (SFTP) are rare neoplasms with unusual histological and clinical features. Although surgery is the treatment of choice for SFTP, tumor recurrence may occur after complete resection, even in tumors with benign histological features. The aim of the study was to identify the clinical and pathological features of SFTP that are associated with a higher risk of recurrence after surgical treatment.

Methods: From May 1995 to September 2002, 18 patients (10 female, 8 male; mean age 58 years) with SFTP underwent complete surgical treatment at our department. Mean follow-up was 61 months. Mean tumor size was 10 cm. The tumors were pedunculated in 10 patients and sessile in 8. Histological features were benign in 16 patients and malignant in 2.

Results: Five-year disease-free survival was 80%. A higher incidence of tumor recurrence was observed when SFTP originated from the parietal pleura, had malignant histological features and a lower expression of progesterone receptors (P < 0.05).

Conclusions: Clinical and pathological characteristics, such as malignant histology, sessile morphology, and a lower expression of progesterone receptors identify SFTP with a higher risk of recurrence after surgery, and which thus require strict follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jso.20562DOI Listing
July 2006

Prognostic factors and analysis of microsatellite instability in resected pulmonary metastases from colorectal carcinoma.

Ann Thorac Surg 2006 Jun;81(6):2008-13

Department of Thoracic Surgery, Scientific Institute H San Raffaele, Milan, Italy.

Background: In this study, we analyze our experience with pulmonary resection for metastases from colorectal carcinoma. The aims were to search for factors influencing prognosis and to investigate the presence of microsatellite instability in the primary tumors and the corresponding lung metastases.

Methods: We identified 81 patients who underwent surgical resection between 1991 and 2004. The microsatellite instability was determined by immunohistochemical evaluation of MSH2 and MLH1 in 117 lesions (41 primary tumors and 76 lung metastases).

Results: Overall 3-, 5-, and 10-year survival rates were 50%, 42%, and 30%, respectively. Univariate analysis showed that stage of the primary tumor (p = 0.037), radicalness of the resection (p = 0.019), and stratification into groups according to the International Registry of Lung Metastases classification (p = 0.039) were prognostic factors. Multivariate analysis showed that stage of the primary tumor (p = 0.030) and the radicalness of the resection (p = 0.014) were independent prognostic factors. All tumors displayed preserved expression of MSH2 and MLH1 and were considered microsatellite stable lesions.

Conclusions: Pulmonary resection of metastases from colorectal carcinoma results in long-term survival in selected patients. Complete resection, stage of the primary tumor and stratification into groups according to the International Registry of Lung Metastases classification were prognostic factors. All the metastases and the corresponding primary tumors were microsatellite stable lesions. This finding seems to demonstrate that pulmonary metastases are infrequent in colorectal carcinomas with microsatellite instability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.athoracsur.2006.01.007DOI Listing
June 2006

Alteration of the E-cadherin/beta-catenin cell adhesion system is common in pulmonary neuroendocrine tumors and is an independent predictor of lymph node metastasis in atypical carcinoids.

Cancer 2005 Mar;103(6):1154-64

Division of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan School of Medicine, Milan, Italy.

Background: To the authors' knowledge, little is known regarding the role of E-cadherin/beta-catenin system dysregulation in pulmonary neuroendocrine tumors.

Methods: E-cadherin and beta-catenin immunoreactivity was evaluated in 10 hyperplastic neuroendocrine tumorlets and 210 neuroendocrine tumors, including 96 typical carcinoids (CTs), 35 atypical carcinoids (ACTs), 49 large cell neuroendocrine carcinomas (LCNECs), and 30 small cell lung carcinomas (SCLCs).

Results: Normal and hyperplastic bronchial neuroendocrine cells expressed E-cadherin/beta-catenin with an orderly distribution along the cell membrane. Neuroendocrine tumors retained beta-catenin expression in all tumors and E-cadherin in most tumors, with the exception of 2% of LCNECs, 3% of SCLCs and 9% of ACTs. E-cadherin showed a prevalent membrane-associated, linear immunoreactivity in CTs, whereas membrane-disarrayed and cytoplasmic staining was seen in most ACTs, LCNECs, and SCLCs (P < 0.001). beta-Catenin exhibited similar immunoreactivity patterns according to tumor type and a close association with E-cadherin subcellular distribution (P < 0.001). Nuclear accumulation of beta-catenin was found only in seven LCNECs and in two SCLCs. In ACTs, disarrayed immunoreactivity for E-cadherin and/or beta-catenin was associated with a nontrabecular growth pattern, altered expression of the cell-motility marker fascin, and lymph node metastases. Furthermore, a disarrayed E-cadherin distribution pattern was associated with the pathologic lymph node classification and the number of involved lymph nodes. Multivariate analysis confirmed that a disarrayed E-cadherin or beta-catenin pattern was an independent predictor of lymph node metastases in patients with ACT.

Conclusions: The subcellular compartmentalization of the E-cadherin/beta-catenin complex was altered in pulmonary neuroendocrine tumors. This likely affects the tumor growth pattern and cell motility of ACT and was correlated with the occurrence of lymph node metastases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.20901DOI Listing
March 2005

Inflammatory pseudotumor of the lung in adults.

Ann Thorac Surg 2005 Feb;79(2):426-32

Department of Thoracic Surgery, Scientific Institute H San Raffaele, Milan, Italy.

Background: Thoracic surgeons have limited experience of inflammatory pseudotumors of the lung owing to their rare occurrence in routine clinical practice.

Methods: We retrospectively investigated the clinicopathologic features of 18 patients with inflammatory pseudotumor of the lung observed between 1992 and 2002.

Results: There were 13 men and 5 women. Median age was 57 years. Eight patients (44%) were symptomatic. Computed tomographic scan showed a solitary nodule (< or =3 cm) in 12 patients, bilateral nodules in 1, and a mass in 5. Two patients had undergone prior incomplete resections. Lobectomy was performed in 5 patients, bilobectomy in 1, segmentectomy in 1, and wedge resection in 11. Complete resection was achieved in 13 patients (72%). There was no operative mortality. Follow-up was complete in all patients (range, 13 to 134 months; median, 63 months). Overall 3-year and 5-year survival rates were 82% and 74%, respectively. Thirteen patients are currently alive with no evidence of disease, 1 is alive with disease, 1 died of unrelated causes, and 3 had a relapse and died. Completeness of resection and lesion size less than or equal to 3 cm were associated with a better survival (p < 0.001 and p = 0.007, respectively). Multivariate Cox analysis confirmed the association between completeness of resection and better survival, which is independent of other clinicopathologic variables (p = 0.02).

Conclusions: This series shows that a significant number of patients with inflammatory pseudotumor of the lung have a poor prognosis and confirms the need for radical resection in the treatment of this unusual entity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.athoracsur.2004.07.077DOI Listing
February 2005

Overexpression of h-prune in breast cancer is correlated with advanced disease status.

Clin Cancer Res 2005 Jan;11(1):199-205

Telethon Institute of Genetics and Medicine, Naples, Italy.

Purpose: The h-prune gene is involved in cellular motility and metastasis formation in breast cancer through interacting with the nm23-H1 protein. The aim of this study was to better define the clinical and pathologic role of h-prune in breast cancer patients.

Experimental Design: Using immunohistochemistry, we assessed h-prune and nm23-H1 protein expression in two series of breast cancer patients: (i) in 2,109 cases with pathologic reports on primary tumors and (ii) in 412 cases with detailed clinical information. To assess the role of DNA amplification in gene activation, the h-prune copy number was evaluated by fluorescence in situ hybridization analysis in 1,016 breast cancer cases.

Results: In the patients tested (n = 2,463), 1,340 (54%) had an increased level of h-prune expression; a positive immunostaining for nm23-H1 was observed in 615 of 2,061 (30%) cases. Overexpression of h-prune was associated with multiple gene copy number at chromosome 1q21.3 in a very limited fraction of cases (68 of 1,016; 6.7%), strongly indicating that alternative pathways induce h-prune activation in breast cancer. Multivariate Cox regression analysis showed that neither h-prune overexpression nor decreased nm23-H1 immunostaining is independent prognostic factors. However, a significant association of h-prune overexpression with either advanced lymph node status (P = 0.017) or presence of distant metastases (P = 0.029) was observed.

Conclusions: Although not significantly correlated with overall survival, positive h-prune immunostaining identifies subsets of breast cancer patients with higher tumor aggressiveness. Further investigations using larger collections of advanced breast cancer patients are required for assessing the predictive role of h-prune in breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
January 2005

Aberrant methylation in the promoter region of the reduced folate carrier gene is a potential mechanism of resistance to methotrexate in primary central nervous system lymphomas.

Br J Haematol 2004 Sep;126(5):657-64

Department of Radiochemotherapy, San Raffaele H Scientific Institute, via Olgettina 60, 20132 Milan, Italy.

We investigated the prevalence and prognostic role of CpG island methylation of the reduced folate carrier (RFC) gene promoter region in primary central nervous system lymphoma (PCNSL) in immunocompetent patients. Genomic DNA from 40 PCNSL was used for methylation-specific polymerase chain reaction and bisulphite genomic sequencing of the RFC promoter region. Human immunodeficiency virus-negative systemic diffuse large B-cell lymphomas (DLBCL) were used as controls (n = 50). The impact on outcome of RFC promoter methylation was assessed in 37 PCNSL patients treated with high-dose methotrexate (HD-MTX)-based chemotherapy +/- radiotherapy. RFC promoter methylation occurred in 12 of 40 (30%) PCNSL and in four of 50 (8%) DLBCL (P = 0.01). Of 37 PCNSL treated with HD-MTX-based chemotherapy, methylation occurred in nine cases (24%, M-PCNSL), while 28 cases (76%, U-PCNSL) were negative. Three M-PCNSL (33%) and 15 U-PCNSL (54%) achieved complete remission (CR) after primary chemotherapy. Logistic regression confirmed the independent association between CR rate and International Extranodal Lymphoma Study Group score (P = 0.03), RFC promoter methylation (P = 0.07) and use of cytarabine (P = 0.08). The 3-year failure-free survival (FFS) and overall survival for M-PCNSL and U-PCNSL was 0% vs. 31 +/- 9% (P = 0.34) and 0% vs. 31 +/- 9% (P = 0.35) respectively. This is the first study to assess the methylation status of the RFC promoter in human tumour samples. RFC methylation is more common in PCNSL compared with systemic DLBCL, and is associated with a lower CR rate to HD-MTX-based chemotherapy. If confirmed in prospective trials on PCNSL treated with HD-MTX alone, these data may suggest the necessity for alternative strategies in M-PCNSL considering the increased risk of MTX resistance by tumour cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1365-2141.2004.05109.xDOI Listing
September 2004

Prognostic significance of cancer-testis gene expression in resected non-small cell lung cancer patients.

Oncol Rep 2004 Jul;12(1):145-51

Department of Thoracic Surgery, Scientific Institute H. San Raffaele, Italy.

MAGE, BAGE and GAGE genes encode T cell-defined tumor-associated antigens (TAA), which are expressed by various human tumors and are silent in normal tissues. Because of their expression pattern these TAA have received attention as potential targets for active immunotherapy and as molecular tumor markers. Both of these features are potentially useful in improving treatment of non-small cell lung cancer (NSCLC). We analyzed the expression of some members of the MAGE, BAGE and GAGE gene families by reverse transcription polymerase chain reaction (RT-PCR) in a cohort of 46 NSCLC patients who underwent complete resection and were followed-up for a median period of 41 months. A substantial proportion (range, 25-41%) of NSCLC expressed MAGE-A1, -A2, -A3, GAGE-1, -2, -8 and MAGE-B2 genes. On the contrary, BAGE and MAGE-B1 were expressed less frequently (17% and 11%, respectively). Overall, 59% of NSCLC patients expressed at least one gene and therefore could be eligible for tumor-specific immunotherapy protocols. Moreover, while MAGE-A, BAGE and MAGE-B genes did not provide any prognostic information, GAGE expression was associated with a worse survival (p=0.05). Multivariate analysis confirmed this association, which is independent of TNM stage and other clinicopathologic variables. In conclusion, the detection of GAGE gene expression by RT-PCR appears to be an independent survival predictor in completely resected NSCLC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
July 2004

Atypical lipomatous tumor: molecular characterization.

Curr Opin Oncol 2004 Jul;16(4):355-8

Department of Pathology, San Raffaele Hospital, Via Olgettina 60, Milan, Italy.

Purpose Of Review: Atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDLs) are one of the more frequent mesenchymal neoplasms and are characterized by specific chromosome aberrations: supernumerary chromosome or giant marker chromosome or both. Extra copies of known oncogenes such as MDM2, CDK4, SAS, HMGA2 and others are present in this abnormal genetic material.

Recent Findings: In the past few years, several papers have further dissected the genetic alterations present in these tumors, allowing the identification of new potential oncogenes.

Summary: ALT/WDLs represent therefore an interesting model for assessing the potential role of these oncogenes, not only in the pathogenesis, but also as a therapeutic target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/01.cco.0000127878.85125.53DOI Listing
July 2004

Prune cAMP phosphodiesterase binds nm23-H1 and promotes cancer metastasis.

Cancer Cell 2004 Feb;5(2):137-49

Telethon Institute of Genetics and Medicine, Via Pietro Castellino 111, 80131 Naples, Italy.

We identify a new enzymatic activity underlying metastasis in breast cancer and describe its susceptibility to therapeutic inhibition. We show that human prune (h-prune), a phosphoesterase DHH family appertaining protein, has a hitherto unrecognized cyclic nucleotide phosphodiesterase activity effectively suppressed by dipyridamole, a phosphodiesterase inhibitor. h-prune physically interacts with nm23-H1, a metastasis suppressor gene. The h-prune PDE activity, suppressed by dipyridamole and enhanced by the interaction with nm23-H1, stimulates cellular motility and metastasis processes. Out of 59 metastatic breast cancer cases analyzed, 22 (37%) were found to overexpress h-prune, evidence that this novel enzymatic activity is involved in promoting cancer metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/s1535-6108(04)00021-2DOI Listing
February 2004

Independent value of fascin immunoreactivity for predicting lymph node metastases in typical and atypical pulmonary carcinoids.

Lung Cancer 2003 Nov;42(2):203-13

Department of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan School of Medicine, Via G. Ripamonti, 435, I-20141 Milan, Italy.

Immunoreactivity for fascin, an actin-bundling protein related to cell motility, has been reported in breast, ovary, pancreas, skin, and non-small cell carcinomas, and associated with more advanced disease stage and poorer prognosis. Data on pulmonary neuroendocrine (NE) tumors, however, are lacking. We evaluated the expression of fascin by immunohistochemistry--using two different monoclonal antibodies--in surgical specimens of pulmonary NE tumors of all the diverse histological types from 128 consecutive patients recruited between 1987 and 2001, and investigated its relationship with the presence of lymph node metastases. Overall, fascin immunoreactivity was detected in 5% of 38 typical carcinoids (TC), 35% of 23 atypical carcinoids (AC), 83% of 40 large-cell neuroendocrine carcinomas (LCNEC), and 100% of 27 small-cell lung carcinomas (SCLC) (P<0.001), Normal NE cells or hyperplastic NE tumorlets were consistently unreactive. No statistically significant differences in fascin immunoreactivity were found between the two antibodies. In TC and AC but not high-grade NE tumors, fascin immunoreactivity closely correlated with the occurrence of lymph node metastases, the pN class and the number of involved lymph nodes (P<0.001). It was also significantly associated with an increased proliferative activity (Ki-67 labeling index >5%) (P=0.020), and with either down-regulation or altered subcellular compartmentalization of E-cadherin (P<0.001) and CD99 (P=0.030), two cell adhesion complexes in pulmonary NE tumors. At multivariate analysis, only fascin emerged as an independent predictor of lymph node metastases in this tumor group (HR 30.28; 95% confidence intervals: 1.59-574.49; P=0.023). This study indicates that fascin immunoreactivity may identify subsets of pulmonary carcinoid patients with different metastatic potential to regional lymph nodes. Targeting the fascin pathway could be a novel therapeutic strategy of pulmonary carcinoids.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/s0169-5002(03)00294-0DOI Listing
November 2003

Extramedullary myeloid cell tumor/granulocytic sarcoma with predilection for serosal surfaces.

Haematologica 2002 Mar;87(3):ECR09

Department of Pathology, Scientific Intitute Ospedale S.Raffaele HSR, Milano, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
March 2002

Chromogranin A expression in neoplastic cells affects tumor growth and morphogenesis in mouse models.

Cancer Res 2002 Feb;62(3):941-6

Department of Biological and Technological Research, San Raffaele H Scientific Institute, via Olettina 58, 20132 Milan, Italy.

Chromogranin A (CgA), a secretory protein expressed by many neuroendocrine cells, has been recognized as a useful tissue and serum marker of neuroendocrine tumors. To investigate the effect of CgA secretion on neoplastic morphogenesis and progression, we have transfected mouse RMA lymphoma and TS/A adenocarcinoma cells with the cDNA encoding human CgA and selected several CgA-positive (secreting) and CgA-negative (nonsecreting) clones. In both models, the growth rate of CgA-positive clones implanted s.c. in nude mice was slower than that of CgA-negative clones. Histological analysis of each RMA tumor showed that CgA-expression was associated with multinodular growth patterns, whereas CgA-negative tumors appeared more compact and similar to wild-type RMA tumors. Moreover, CgA production was associated with increased tumor necrosis. The number of nodules in each RMA tumor correlated with the serum levels of CgA (n = 40, r = 0.537, P = 0.0004). The reduced growth rate of CgA-positive RMA and TS/A tumors was not related to reduced in vitro proliferation or to changes in cell adhesion and shape, suggesting that the mechanism is indirect and host-mediated. These results suggest that abnormal secretion of CgA by neuroendocrine neoplastic cells could affect neoplastic growth and morphogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2002