1,721,037 research outputs found

    HER2 heterogeneity in personalized therapy of gastro-oesophageal malignancies: An overview by different methodologies

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    Human epidermal growth factor receptor-2 (HER2)-expression gastro-oesophageal adenocarcinomas (GEA) gained interest as an important target for therapy with trastuzumab. In the current review, we focused the current knowledge on HER2 status in dysplastic and neoplastic gastric conditions, analyzing the methodological procedures to identify HER2 expression/amplification, as well as the proposed scoring recommendations. One of the most relevant questions to evaluate the useful impact of HER2 status on therapeutic choice in GEAs is represented by the significant heterogeneity of HER2 protein and gene expression that may affect the targeted treatment selection. Future development of biotechnology will continue to evolve in order to offer more powerful detection systems for the assessment of HER2 status. Finally, liquid biopsy as well as mutation/amplification of several additional genes may furnish an early detection of secondary HER2 resistance mechanisms in GEAs with a better monitoring of the treatment response

    A retroperitoneal cyst with unusual urinary histogenesis: clinical and immunomorphological characteristics

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    Primary retroperitoneal cysts are rare benign lesions which often present as an incidental radiological finding and also cause abdominal symptoms. A 47-year-old woman was admitted to the surgery unit because of right-sided abdominal pain. Computed tomographic scan investigation confirmed a circumscribed, oval, dishomogeneous mass in the right anterior pararenal space. The final diagnosis was obtained after laparotomy excision and pathological evaluation. Immunohistochemical profile was characterized by positive expression of epithelial cystic cells for CKAE1/AE3, CK7, CK8, and CK18, with EMA sustaining the diagnosis of a benign retroperitoneal cyst of urinary system origin

    HER2 status in unusual histological variants of gastric adenocarcinomas

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    Aim To investigate HER2 status in a cohort of 109 gastric adenocarcinomas also including unusual variants, such as 14 hepatoid (HAS) and 9 mitochondrion-rich (MRC), characterised by an opposing clinical behaviour.Methods and Results Using HercepTest (DAKO) and FISH test (pharmDx DAKO), HER2 overexpression/amplification was encountered in 23 of 109 (21.10%) of all gastric adenocarcinomas. A progressive increase in HER2 overexpression was observed moving from the poorly cohesive histotype to MRC, tubular adenocarcinomas and HAS. A statistically significant difference was found between poorly cohesive carcinomas and the others; a similar significant difference was encountered between HAS and all other variants of adenocarcinoma. HER2 overexpression was significantly associated with high grade, advanced stage, high Ki-67 labelling index value and death from gastric cancer. Multivariate analysis identified HER2 overexpression as an independent unfavourable prognostic variable for adenocarcinomas as a whole and also for the HAS variant.Conclusions Trastuzumab has been confirmed as an additional useful therapeutic standard option for patients with HER2-positive advanced gastric cancers, and also in aggressive variants of adenocarcinomas such as HAS

    Lactoferrin immuno-expression in human normal and neoplastic bone tissue

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    Lactoferrin (Lf) expression was investigated by using a Lf monoclonal antibody in 50 formalin-fixed and paraffin-embedded human bone tumours [10 giant cell tumours (GCTs), 7 osteoid osteomas, 6 ossifying fibromas, 19 enchondromas, 2 chondroblastomas, 2 chondrosarcomas, 2 chondroblastic osteosarcomas, 1 myeloma and 1 adamantinoma] as well as in 8 samples of adult and foetal human normal bone specimens. In addition, the immunohistochemical expression of the estrogen receptor (ER), progesterone receptor (PR) and Ki-67 antigen was analysed on parallel sections from the same specimens. Quantification of Lf immunoreactivity was performed by using an Intensity Distribution (ID) score. Lf immuno-expression with a variable ID score was encountered in 19/50 tumours and specifically in 10/10 GCTs, in 5/7 osteoid osteomas, in 2/2 chondroblastomas as well as in the adamantinoma and in the myeloma. With reference to normal bone samples, Lf was expressed by the osteoblasts only in the foetal bone. No immunoreactivity for ER and PR was encountered in all neoplastic samples, and no correlation was found between Lf and sex steroid hormone receptor (ER and PR) immuno-expression. Even more, no association was evidenced between Lf immuno-reactivity and the growth fraction of the tumours, reflected by the Ki-67 labelling index. Lf expression in the osteoblastic lineage of bone-forming tumours, together with its presence in the osteoblasts of foetal bone, requires further investigations, although it cannot be ruled out that Lf might be involved in the bone formation in humans, similarly to what has been demonstrated in other species

    Immunolocalization of lactoferrin in cartilage-forming neoplasms

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    Lactoferrin (Lf) is an 80-kDa basic glycoprotein, a member of the transferrin family of iron-binding proteins. Lf immunoreactivity has been extensively investigated in many neoplastic tissues. Recently, Lf expression was documented in the osteoblastic lineage of bone-forming tumors as well as in osteoblasts of fetal bone.Lactoferrin (Lf) immunoexpression was investigated in 30 human cartilage-forming tumors [15 enchondromas, 6 osteochondromas, 3 chondroblastomas (CBL), 3 chondrosarcomas, and 3 chondromyxoid fibromas (CMF)] as well as in human normal bone specimens and cartilaginous tissues obtained at autopsy from 5 adults and 3 fetuses.In addition, the immunohistochemical expression of Ki-67 antigen was analyzed on parallel sections from the same specimens. Quantification of Lf immunoreactivity was performed by using an intensity distribution (ID) score.Lf immunoexpression with a variable ID score was encountered exclusively in 3 of 3 chondroblastomas and in 3 of 3 chondromyxoid fibromas. Lf immunoreactivity in these tumors, in clear contrast with the Lf absence in enchondromas, osteochondromas, and chondrosarcomas, may suggest a different histogenesis of the former. In agreement with this histogenetic origin, we detected Lf in the chondroblasts and osteoblasts within the fetal tissue, whereas no immunoreactivity was found in the corresponding adult cells. No significant associations were found between the Lf immunoexpression and the Ki 67 LI of the tumors of our series.The presence of Lf in neoplastic cells of CBL and CMF, as well as in fetal cartilaginous tissue, may reflect a less mature phenotype of these tumors

    Osteoblastic meningiomas: clinico-pathological and immunohistochemical features of an uncommon variant

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    Osteoblastic meningioma is a rare variant of meningioma characterized by the presence of a variable number of bone spicules within the tumor parenchyma. Its histogenesis has not been yet fully clarified. Herein we report clinical and histological findings and expression of bone matrix proteins (osteocalcin and ostepontin) observed in seven osteoblastic meningiomas. None of the cases displayed recurrences or significant re-growth after partial resection. In 5/7 cases the osseous component occurred in association with psammoma bodies and dystrophic calcification. Interestingly, foci composed of immature bone trabeculae, mineralized chondroid matrix, and osteoclasts were found in one of the two cases with no psammoma bodies or calcification, suggesting enchondral ossification. Positive staining for osteocalcin, which is a marker of terminal osteoblastic differentiation, was observed within the bone spicules in all meningiomas, but not in the chondroid mineralized matrix. On the other hand, immuno-expression of osteopontin, an early osteogenic marker, was observed in the osteoclasts and in mature and immature bone spiculae, calcification, and psammoma bodies. Even more, osteopontin was extensively expressed by the neoplastic cells of cases without calcification or psammoma bodies, suggesting acquisition of osteoblastic phenotype in these meningiomas. In conclusion, osteoblastic meningioma seems to be an indolent variant of meningiomas characterized by a slow growth and good prognosis. Our histological and immunohistochemical findings suggest that bone formation may occur through two different pathways, i.e., as the final step of calcification or through a metaplastic mechanism in cases with absent calcification or psammoma bodies

    High-grade urothelial carcinoma of the urinary bladder showing acquisition of microcystic histology in the penile metastasis: histogenetic considerations

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    Microcystic urothelial carcinoma is a rare variant of transitional cell carcinoma with an indefinite prognostic significance. Herein, we report for the first time the acquisition of microcystic histology in the penile metastasis of a high-grade urothelial carcinoma of the urinary bladder. The patient died of disseminated disease six months later. The immunohistochemical evaluation of mucin expression in the primitive and metastatic tumor suggests that the microcystic histotype may descend from the primitive urothelial carcinoma through a process of dedifferentiation and subsequent redifferentiation. In conclusion, the acquisition of microcystic histology seems to be associated with an aggressive clinical course of the urothelial carcinoma, as already suggested by other authors. Future studies investigating mucin expression in microcystic urothelial carcinoma may help to define the histogenesis of this tumor. (C) 2009 Published by Elsevier GmbH

    Lymph node fine-needle cytology: Beyond flow cytometry

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    Lymph node (LN) fine-needle cytology (FNC) coupled with flow cytometry immunophenotyping provides relevant information for the diagnosis of non-Hodgkin lymphoma (NHL). Numerous studies have shown FNC samples to be suitable for different molecular procedures; in this review, some of the molecular procedures most commonly employed for NHL are briefly described and evaluated in this perspective. Fluorescence in situ hybridization and chromogenic in situ hybridization are briefly described. Polymerase chain reaction (PCR)-based assays are used to identify and quantify mutations and translocations, namely immunoglobulin (IGH) and T-cell receptor rearrangements by clonality testing and IGVH somatic hypermutations either by Sanger sequencing, single-strand conformational polymorphisms or RT-PCR strategies. High-Throughput technologies (HTT) encompass numerous and different diagnostic tools that share the capacity of multiple molecular investigation and sample processing in a fast and reproducible manner. HTT includes gene expression profiling, comparative genomic hybridization, single-nucleotide polymorphism arrays and next-generation sequencing technologies. A brief description of these tools and their potential application to LN FNC is reported. The challenge for FNC will be to achieve new knowledge and apply new technologies to FNC, exploiting its own basic qualities
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