0000000001253335
AUTHOR
Francisco Giner
Controversial issues in soft tissue solitary fibrous tumors: A pathological and molecular review
The clinical evolution of solitary fibrous tumor (SFT) remains unclear. Although various clinical, morphological and molecular criteria may indicate increased risk of malignancy, some SFT can still progress despite having a clearly benign appearance. Various risk stratification systems have been proposed, but unfortunately they are not sufficient to precisely determine the malignant potential. In this review, we discuss current knowledge on SFT, focusing on the following controversial issues: (i) the diverse morphologic spectrum: 'the great simulator;' (ii) malignant transformation or dedifferentiation; (iii) current risk stratification systems; and (iv) molecular factors associated with cl…
Uterine glomeruloid hemangioma in a patient without POEMS syndrome.
Cutaneous glomeruloid hemangioma is a hallmark of POEMS syndrome. These patients have elevated serum levels of vascular endothelial growth factor. The authors report an extracutaneous uterine glomeruloid hemangioma in an 82-year-old woman with a history of breast and endometrial carcinomas. Within the lumen of myometrial vessels, a lobular, glomeruloid proliferation of capillary-like CD31 and vascular endothelial growth factor receptor-1-positive endothelial cells was found. The capillary loops were lined by endothelial cells, most of them containing PAS-positive and immunoglobulin-positive eosinophilic hyaline globules (thanatosomes). This vascular proliferation was consistent with a glom…
Chemokine Expression Is Involved in the Vascular Neogenesis of Ewing Sarcoma: A Preliminary Analysis of the Early Stages of Angiogenesis in a Xenograft Model.
Background Ewing sarcoma (EWS) is the second most common bone cancer in pediatric patients. Angiogenesis is a major factor for tumor growth and metastasis. Our aim was to carry out a histological, immunohistochemical, and molecular characterization of the neovascularization established between xenotransplanted tumors and the host during the initial phases of growth in nude mice in three angiogenesis experiments (ES2, ES3, and ES4). Methods The original human EWS were implanted subcutaneously on the backs of three nude mice. Tumor pieces 3 mm–4 mm in size from early passages of Nu432, Nu495, and Nu471 were also implanted subcutaneously on the backs of three sets (ES2, ES3, and ES4) of athymi…
Gain of MYCN region in a Wilms tumor-derived xenotransplanted cell line.
Wilms tumor is one of the most common pediatric malignant tumors of the kidney. Although the WT1 gene, located at 11p13, has been proven to be implicated in the development of Wilms tumor, other genes such as MYCN are also involved. The purpose of this study is to genetically characterize a Wilms tumor metastasis xenotransplanted in nude mice. Immunogenotype evolution of the xenografts material was monitored for 29 months using molecular techniques, fluorescent in situ hybridization and multiplex ligation-dependent probe amplification, in addition to immunohistochemistry in tissue microarrays. Genetic alterations present in the original tumor and retained in the xenotransplanted tumor were …
The Epithelial Mesenchymal Transition Process in Wilms Tumor
Background Until now, only a few mouse-transplanted human tumors or experimental Wilms tumor (WT) cell lines have been described. The aim of this study was to show the biological behavior, including histology, immunohistochemistry (IHC), and molecular biology, of a WT including the original tumor and metastasis transferred into nude mice and followed for successive generations in xenografts. Methods A WT metastasis was xenotransplanted into nude mice and the mice was monitored for 7 passages over a period of 29 months; the original neoplasm was comparatively studied. The morphology was evaluated by optical and electron microscopy. The protein expression was analyzed by immunohistochemistry …
Prognostic Impact of pT Stage and Peritoneal Invasion in Locally Advanced Colon Cancer
BACKGROUND: TNM stage has been identified as an independent variable for local recurrence and survival after colon cancer resection. It is still unclear whether peritoneal invasion (pT4a) is a risk factor for adverse oncologic outcome or whether these patients have better results compared with contiguous organs infiltration (pT4b), independent from nodal status (pN). OBJECTIVE: The purpose of this study was to analyze whether peritoneal invasion is an independent risk factor for worse oncologic outcome after curative colon cancer resection. DESIGN: This was a retrospective analysis with multivariate regression of a prospective database, according to Strengthening the Reporting of Observatio…
Tissue microarrays analysis in chondrosarcomas: light microscopy, immunohistochemistry and xenograft study
Abstract Background Chondrosarcoma (Chs) is the third most frequent primary malignant tumour of bone and can be primary or secondary, the latter results mainly from the malignant transformation of a benign pre-existing tumour. Methods All the cases diagnosed as Chs (primary tumours, recurrences and/or metastasis and xenotransplanted Chs) from the files of our Department were collected. Only cases with paraffin blocks available were selected (Total 32 cases). Six Tissue Microarrays (TMAs) were performed and all the cases and biopsies were distributed into the following groups: a) only paraffin block available from primary and/or metastatic tumours (3 TMAs), b) paraffin block available from p…
Right ventricular involvement in anterior myocardial infarction: a translational approach.
Aims The aim of the present study was to evaluate the involvement of the right ventricle (RV) in reperfused anterior ST-elevation myocardial infarction (STEMI). Methods and results Left anterior descending (LAD)-perfused area (using thioflavin-S staining after selective infusion in proximal LAD artery, %), infarct size (using triphenyltetrazolium chloride staining, %), and salvaged myocardium (% of LAD-perfused area) in the right and left ventricle (LV) were quantified in a 90-min LAD occlusion 3-day reperfusion model in swine ( n = 8). Additionally, we studied, using cardiovascular magnetic resonance, 20 patients with a first STEMI due to proximal LAD occlusion treated with primary angiopl…
Neuroendocrine differentiation in a large series of genetically-confirmed Ewing’s sarcoma family tumor: Does it provide any diagnostic or prognostic information?
Given the potential for neuroendocrine differentiation in Ewing's sarcoma family of tumors (ESFT), we aimed to determine neuroendocrine expression in a large series of genetically-confirmed ESFT and its prognostic significance in clinically-localised neoplasms (n = 176). Slides prepared from tissue microarrays were stained for Insulinoma-associated protein 1 (INSM1), CD56, chromogranin-A and synaptophysin. INSM1 expression was present in 59% of ESFT, while synaptophysin, chromogranin-A and CD56 were expressed in only 13%, 8% and 5% of ESFT, respectively. Histological subtypes were only significantly correlated with INSM1 (p = 0.032) or CD56 (p = 0.016) immunoexpression. Regarding prognosis,…
High-risk gastrointestinal stromal tumour (GIST) and synovial sarcoma display similar angiogenic profiles: a nude mice xenograft study
Background: Gastrointestinal stromal tumour (GIST) is the most common primary mesenchymal tumour of the gastrointestinal tract. Spindle cell monophasic synovial sarcoma (SS) can be morphologically similar. Angiogenesis is a major factor for tumour growth and metastasis. Our aim was to compare the angiogenic expression profiles of high-risk GIST and spindle cell monophasic SS by histological, immunohistochemical and molecular characterisation of the neovascularisation established between xenotransplanted tumours and the host during the initial phases of growth in nude mice. Methods: The angiogenic profile of two xenotransplanted human soft-tissue tumours were evaluated in 15 passages in nude…
A tissue microarray study of osteosarcoma: histopathologic and immunohistochemical validation of xenotransplanted tumors as preclinical models.
Osteosarcomas (OS) are aggressive neoplasms with a wide range of morphologic patterns.OS cases (primary and xenotransplanted) with paraffin blocks available were collected and included in tissue microarrays (TMAs). A morphologic evaluation including the different passages in mice was carried out according to the new WHO criteria. In addition, TMAs were analyzed with a wide panel of immunohistochemical (IHC) markers (osteonectin, osteocalcin,cytokeratin, S100, Sox-9, Ki-67, Bcl-2, p53, p16, survivin, CD99, and caveolin-1).A total of 61 cases were collected. The distribution of the cases according to the histopathologic pattern was: 38 osteogenic OS, 8 primary chondrogenic OS, 2 primary telan…
The Role of Immunohistochemistry in Rhabdomyosarcoma Diagnosis Using Tissue Microarray Technology and a Xenograft Model
Rhabdomyosarcomas (RMS) may resemble other non-myogenic sarcomas and malignant rhabdoid tumor (MRT). Alveolar rhabdomyosarcoma (ARMS) often harbors a typical translocation, but embryonal rhabdomyosarcoma (ERMS) lacks any specific rearrangement. Histopathology is not always sufficient for an unequivocal diagnosis, necessitating ancillary studies, including immunohistochemistry (IHC). Sixteen genetically tested RMS and two MRT were xenografted and followed in successive passages. Tissue microarrays were constructed including samples from original and xenograft tumors. Desmin, myogenin, CK, EMA, INI1, LSD1, AP2 beta, fibrillin-2, HMGA2, nestin, and SIRT1 were tested using immunohistochemical s…
Ki-67 immunoexpression and radiological assessment of necrosis improves accuracy of conventional and modified core biopsy systems in predicting the final grade assigned to adult-soft tissue sarcomas. An international collaborative study
Based on the French Federation Nationale des Centers de Lutte Contre le Cancer (FNCLCC) grading system, this study assesses the accuracy of conventional and modified core biopsy (CB) systems in predicting the final grade (low vs high) assigned to the resected specimen. Substituting Ki-67 immunoexpression for mitotic count, and radiological for histological assessment of necrosis, we used two modified FNCLCC CB grading systems: (1) Ki-67 immunoexpression alone, and (2) Ki-67 plus radiological assessment of necrosis. We graded 199 soft tissue sarcomas (STS) from nine centers, and compared the results for the conventional (obtained from local histopathology reports) and modified CB systems wit…
A Proposal for Novel Standards of Histopathology Reporting for D3 Lymphadenectomy in Right Colon Cancer: The Mesocolic Sail and Superior Right Colic Vein Landmarks
Background Strong agreement exists concerning the standards of pathologic reporting for total mesorectal excision and complete mesocolic excision. It represents a quality standard that correlates with survival. However, no agreed standards of reporting are available to define D3 lymphadenectomy for right colectomy. Objective The purpose of this study was to define anatomopathological standards of specimen quality obtained from the surgical specimen when an oncologic right hemicolectomy with D3 lymphadenectomy has been correctly performed. Design This study was conducted in 2 different phases. The first part consisted of a cadaver-based study of right colon anatomy, and the second part consi…
Solitary Fibrous Tumor: Integration of Clinical, Morphologic, Immunohistochemical and Molecular Findings in Risk Stratification and Classification May Better Predict Patient outcome
Although solitary fibrous tumors (SFTs) have an unpredictable evolution, some specific clinicopathologic factors have been associated with the final outcome. We retrieved clinical, pathological and molecular data of 97 patients with a histological diagnosis of SFT and Signal transducer and activator of transcription 6 (STAT6) positivity. We retrospectively studied the pathological factors predictive of recurrence/metastasis and compared them with the clinical outcome. A wide immunohistochemical study and molecular analysis to detect NAB2/STAT6 gene fusion, tumor protein-53 (TP53) and/or (telomerase reverse transcriptase) TERT promotor mutation were performed. The risk of metastasis was calc…
The Augmented User: a Wearable Augmented Reality Interface
In this paper, 'The Augmented User' project is presented, a new Augmented Reality (AR) system based on the ARToolKit and MRXToolKit technologies. We have developed an innovative system in which the user is visible in the AR scenario and indispensable part of the final result: he/she is in fact the carrier of the markers that are recognized by the system allowing his/her own transformation; this opens the possibilities of the users that are immersed in an AR system, being at the same time the augmented matter and the spectator. We also introduce two interesting applications for our system: the 'changing personalities' game and the 'image carrousel' performance, as simple examples of the mult…