1,721,026 research outputs found
Mixed adenocarcinomas of the lung: place in new proposals in classification, mandatory for target therapy
No full textCONTEXT: Lung cancer is one of the most frequent and lethal malignant neoplasms, but knowledge regarding the molecular basis of its pathogenesis is far from complete due to the striking diversity of different forms. The current lung cancer classification (World Health Organization 2004) can efficiently distinguish clinically relevant major subtypes (small cell and non-small cell carcinomas), but its results are partly inadequate when facing prognostic and therapeutic decisions for non-small cell carcinomas, especially for the group of tumors classified as adenocarcinoma. Lung adenocarcinoma comprises a heterogeneous group of tumors characterized by diverse morphologic features and molecular pathogenesis. The category of mixed adenocarcinomas includes most adenocarcinomas (approximately 80%) and, according to World Health Organization criteria, is defined by the occurrence of a mixed array of different patterns (acinar, papillary, bronchioloalveolar, solid with mucin). The histologic recognition of mixed adenocarcinoma is subjective and cannot consistently discriminate between responders and nonresponders to new targeted therapies (eg, tyrosine kinase inhibitors). Diagnostic problems are mainly related to the poor reproducibility of histologic criteria, especially when applied in small biopsies and cytology, and to the difficulty in assigning each form to a precisely defined entity, as needed by updated therapeutic approaches. In this evolving scenario, pathologists face new challenging diagnostic roles that include not only the precise morphologic definition of carcinoma subtypes but also their molecular characterization. OBJECTIVE: To use a comprehensive critical analysis reconciling the overwhelming variety of biologic, morphologic, molecular, and clinical data to define new classification schemes for lung adenocarcinoma. DATA SOURCES: Scientific literature and personal data were used. CONCLUSIONS: A new classification approach should redefine lung adenocarcinoma heterogeneity reconciling classic morphology, immunophenotypic and molecular features of neoplastic cells, and also relevant information provided by stem cell biology. This approach, which has been already successfully applied in World Health Organization classification of other tumors, could improve the recognition of new reproducible profiles for adenocarcinomas, more closely and reproducibly related to clinical features and response to specific therapies, limiting the use of "wastebasket" categories such as mixed adenocarcinoma
Bronchoalveolar lavage in malignancy
No full textThe microphthalmia transcription factor/transcription factor E (TFE)-family translocation renal cell carcinomas
bear specific translocations that result in overexpression of TFE3 or TFEB. TFE3 fusion gene product overexpression
occurs as consequence of different translocations involving chromosome Xp11.2, whereas TFEB
overexpression is the result of the specific translocation t(6;11)(p21;q12), which fuses the Alpha gene to TFEB.
Both TFE3 and TFEB are closely related members of the microphthalmia transcription factor/TFE-family, which
also includes TFEC and microphthalmia transcription factor. These transcription factors have overlapping
transcriptional targets. Overexpression of microphthalmia transcription factor has been shown to mediate the
expression of cathepsin-K in osteoclasts. We hypothesize that the overexpression of the related TFE3 fusion
proteins and TFEB in translocation renal cell carcinomas may have the same effect. We studied cathepsin-K in
17 cytogenetically confirmed microphthalmia transcription factor/TFE-family translocation renal cell carcinomas.
Seven cases showed a t(6;11)(p21;q12), ten cases showed translocations involving Xp11.2; five cases
t(X;1)(p11;q21) resulting in a PRCC–TFE3 gene fusion; three cases t(X;1)(p11;p34) resulting in a PSF–TFE3 gene
fusion, one t(X;17)(p11;q25) resulting in an ASPL–TFE3 gene fusion, and one t(X;3)(p11;q23) with an unknown
TFE3 gene fusion. As control we analyzed cathepsin-K in 210 clear cell, 40 papillary, 25 chromophobe renal
cell carcinomas and 30 oncocytomas. All seven TFEB translocation renal cell carcinomas were labeled for
cathepsin-K. Among the cytogenetically confirmed TFE3 translocation renal cell carcinomas, 6 out of 10 were
positive. None of the other renal neoplasms expressed cathepsin-K. We conclude the following: (1) cathepsin-K
is consistently and strongly expressed in TFEB translocation renal cell carcinomas and in 6 of 10 TFE3 translocation
renal cell carcinomas. (2) Cathepsin-K immunolabeling in both TFE3 and TFEB translocation renal cell
carcinomas distinguishes these neoplasms from the more common adult renal cell carcinomas, and may be
a specific marker of these neoplasms. (3) These results further support the concept that the overexpression of
TFE3 or TFEB in these neoplasms activates the expression of genes normally regulated by microphthalmia
transcription factor in other cell types.
Modern Pathology (2009) 22, 1016–1022; doi:10.1038/modpathol.2009.58; published online 24 April 200
HLA-DR expression in liver in human HIV infection
No full textIn order to clarify the relationship between HLA-DR antigen expression in the liver and human HIV infection, we studied 66 non-autopsy specimens obtained from HIV-infected patients with and without AIDS; 33 biopsies from HIV-negative patients were considered for control purposes. All biopsies were immunohistochemically tested with monoclonal antibody TAL-1B5, reacting with the alpha-chain subunit of HLA-DR in the avidin biotin complex method. We found occasional and usually weak HLA-DR expression on hepatocytes and biliocytes. By comparison with controls, HIV-positive cases showed a significantly higher percentage of HLA-DR immunoreactivity on hepatic artery and portal vein endothelial cells. No relationship was demonstrated between HLA-DR endothelial expression and the CD4+ lymphocyte count or grade of portal/periportal inflammation in the liver. The biological significance of HLA-DR expression on intrahepatic vascular endothelial cells in HIV infection still remains to be clarified
HLA-DR EXPRESSION IN LIVER IN HUMAN HIV-INFECTION
No full textIn order to clarify the relationship between HLA-DR antigen expression in the liver and human HIV infection, we studied 66 non-autopsy specimens obtained from HIV-infected patients with and without AIDS; 33 biopsies from HIV-negative patients were considered for control purposes. All biopsies were immunohistochemically tested with monoclonal antibody TAL-1B5, reacting with the alpha-chain subunit of HLA-DR in the avidin biotin complex method. We found occasional and usually weak HLA-DR expression on hepatocytes and biliocytes. By comparison with controls, HIV-positive cases showed a significantly higher percentage of HLA-DR immunoreactivity on hepatic artery and portal vein endothelial cells. No relationship was demonstrated between HLA-DR endothelial expression and the CD4+ lymphocyte count or grade of portal/periportal inflammation in the liver. The biological significance of HLA-DR expression on intrahepatic vascular endothelial cells in HIV infection still remains to be clarified
EPITHELIAL STEM CELL EXHAUSTION IN THE PATHOGENESIS OF IDIOPATHIC PULMONARY FIBROSIS
No full textNew paradigms have been recently proposed in the pathogenesis of idiopathic pulmonary fibrosis (IPF), evidencing that in IPF the cumulative action of an accelerated parenchymal senescence determined by either telomere dysfunction or genetic defects, together with the concurrent noxious activity of tobacco smoking, are able to severely compromise the regenerative potential of parenchymal epithelial stem cells, triggering a cascade of molecular signals and events (scarring, bronchiolar proliferation, abnormal remodelling) eventually leading to severe and irreversible functional impairment. New pathogenic schemes focus on the complex molecular mechanisms driving in a vicious circle the different signalling pathways (e.g. Wnt/ -catenin, TGF-beta, caveolin-1, etc.) potentially involved in epithelial-mesenchymal transition and irreversible lung remodelling. (Sarcoidosis Vasc Diffuse Lung Dis 2010; 27: 7-18
The pathologist's role in the diagnosis of idiopathic pulmonary fibrosis
No full textDiagnosis of idiopathic pulmonary fibrosis (IPF) is challenging, and the cooperation between different specialists including pulmonologists, radiologists and pathologists is highly recommended in order to optimize the diagnostic process, avoiding unnecessary and harmful invasive procedures. The recognition of the usual histological pattern of interstitial pneumonia is not easy in some cases, and immunohistochemical markers can be applied to better visualize subtle microenvironmental changes in lung parenchyma. New data regarding the complex pathogenesis of IPF is helping to understand the severe lung remodeling that characterizes this disease, and may also provide new diagnostic criteria
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