Stromal reaction and prognosis in acinic cell carcinoma of the salivary gland.

INTRODUCTION: Primary acinic cell carcinoma (ACC) is an uncommon malignant neoplasm of the salivary gland (SG), which usually presents as slow growing tumor. CASE REPORT: We reported a 69-year-old woman with tumor in the right parotid gland with a 5-year progress. Biopsy sections revealed a hybrid form of ACC with a low- and high-grade component and prominent lymphoid tissue in tumor stroma. Immunohistochemistry was performed to define the molecular profile of this unusual ACC, with special interest for stromal influence on to the proliferative activity of ACC with dedifferentiation. We detected that the level and the type of stromal lymphoid reaction (particularly CD8+/CD4+ ratio) had a significant influence on to Ki-67 index in the high-grade component of ACC, as well as the involvement of the CXCR4 signaling axis in the stromal reaction influence. CONCLUSION: We suggest that tumor stroma may be a source of potential new tumor biomarkers which can determine the aggressivity of this tumor.

Ossifying chondrolipoma of the tongue.

INTRODUCTION: Chondrolipomas and osteolipomas are uncommon variants of lipomatous tumors. CASE REPORT: We presented a 60-year-old woman with ossifying chondrolipoma of the tongue. Clinical examination revealed a firm nodular mass, located in the midline of the posterior region on the dorsal surface of the tongue. Histologically, the lesion was well-delimited showing areas of mature adipocytes arranged in lobules and separated by fibrous connective tissue septa, islands of mature cartilaginous tissue and osseous metaplasia. Trabeculae of lamellar bone within a fibro-fatty background were visible throughout the tumor. The cartilaginous areas merging centrally with bone formation and fatty marrow tissue were present, as well as the hematopoietic elements in the fatty marrow. The bone forming was found to be through both membranous and enchondral mechanisms. CONCLUSION: Ossifying chrondrolipoma with hematopoietic elements is extremely unusual lesion. This interesting entity should be kept in mind in the differential diagnosis of lingual lesions.

Ovarian epithelial cancer stem cells.

The last decade witnessed an explosion of interest in cancer stem cells (CSCs). The realization of epithelial ovarian cancer (EOC) as a CSC-related disease has the potential to change approaches in the treatment of this devastating disease dramatically. The etiology and early events in the progression of these carcinomas are among the least understood of all major human malignancies. Compared to the CSCs of other cancer types, the identification and study of EOC stem cells (EOCSCs) is rather difficult due to several major obstacles: the heterogeneity of tumors comprising EOCs, unknown cells of origin, and lack of knowledge considering the normal ovarian stem cells. This poses a major challenge for urgent development in this research field. This review summarizes and evaluates the current evidence for the existence of candidate normal ovarian epithelial stem cells as well as EOCSCs, emphasizing the requirement for a more definitive laboratory approach for the isolation, identification, and enrichment of EOCSCs. The present review also revisits the ongoing debate regarding other cells and tissues of origin of EOCs, and discusses early events in the pathogenesis of this disease. Finally, this review discusses the signaling pathways that are important regulators of candidate EOCSC maintenance and function, their potential role in the distinct pathogenesis of different EOC subtypes, as well as potential mechanisms and clinical relevance of EOCSC involvement in drug resistance.

Glioblastoma multiforme stem cells.

Glioblastoma multiforme (GBM) is an aggressive, malignant, and lethal brain tumor, resistant to all current forms of treatment. The rapidly emerging focus on cancer stem cells embodies a paradigm shift in our understanding of tumor pathogenesis, while the development of powerful genome-wide screening techniques has provided cause for optimism related to the development of more reliable therapies primarily targeting GBM stem cells (GBMSCs). There are promising mounting data on providing new molecular targets and predictive markers of response, leading to more effective therapies of GBM, guided by patient-specific genetic and epigenetic profiling. However, the achievement of efficient GBMSC targeting also requires an adequate understanding of the unique microenvironment, and the relationship with the immune system in the central nervous system (CNS) and CNS tumors. The endogenous immune regulation is likely to limit or abrogate the efficacy of the host's immune response, as well as the developed immunotherapeutic strategies at present. Therefore, a comprehensive understanding of the mechanisms underlying the GBM-induced immunosuppression is indispensable. This review presents a summary of the present knowledge both on GBMSCs and the GBM, and/or GBMSC-related mechanisms of developing both local and systemic immunosuppression, of which an understanding may lead to the development of the novel and effective therapeutic strategies.

Primary gallbladder melanoma in dysplastic nevus syndrome: report of case and literature review.

A case of gallbladder malignant melanoma in a 62-year-old woman is reported. The gallbladder, resected for tumor mass seen on ultrasound examination, revealed neoplastic epithelioid cells with dark granules in the cytoplasm. These cells with pigment were positive immunohistochemically for S-100, HMB45 and vimentin. The patient, affected by dysplastic nevus syndrome, had a history of a melanoma in situ in her left upper arm that was excised 11 years ago. This is only the second case reported to date of primary malignant melanoma in dysplastic nevus syndrome.

Urothelial cancer stem cells.

There is mounting evidence supporting the idea that tumors, similar to normal adult tissues, arise from a specific stem-like cell population, the cancer stem cells (CSCs), which are considered as the real driving force behind tumor growth, the ability to metastasize, as well as resistance to conventional antitumor therapy. The concept that cancer growth recapitulates normal proliferative and/or regenerative processes, even though in very dysfunctional ways, has tremendous implications for cancer therapy. The rapid development of the CSC field, shoulder to shoulder with powerful genome-wide screening techniques, has provided cause for optimism for the development of more reliable therapies in the future. However, several important issues still lie ahead. Recent identification of a highly tumorigenic stem-like compartment and existence of urothelial differentiation programs in urothelial cell carcinomas (UCCs) raised important questions about UCC initiation and development. This review examines the present knowledge on CSCs in UCCs regarding the similarities between CSCs and the adult urothelial stem cells, potential origin of urothelial CSCs, main regulatory pathways, surface markers expression, and the current state of CSC-targeting therapeutic strategies.

Urinary exosomes.

Exosomes are nanovesicles of endocytic origin that are secreted into the extracellular space or body fluids when a multivesicular body (MVB) fuses with the cell membrane. Interest in exosomes intensified after their description in antigen-presenting cells and the observation that they can significantly moderate immune responses in vivo. In the past few years, several groups have reported on the secretion of exosomes by almost all cell types in an organism. In addition to a common set of membrane and cytosolic molecules, exosomes harbor unique subsets of proteins, reflecting their cellular source. Major research efforts were put into their surprisingly various biological functions and in translating knowledge into clinical practice. Urine provides an exciting noninvasive alternative to blood or tissue samples as a potential source of disease biomarkers. Urinary exosomes (UE) became the subject of serious studies just a few years ago. A recent large-scale proteomics-based study of normal UE revealed a myriad of proteins, including disease-related gene products. Thus, UE have valuable potential as a source of biomarkers for early detection of various types of diseases, monitoring the disease evolution and/or response to therapy. As a relatively new field of research, it still faces many challenges, but UE have already shown some straightforward potential.

Challenges of genomics and proteomics in nephrology.

An increasing number of patients suffering from renal diseases and limitations in standard diagnostic and therapeutic approaches has created an intense interest in applying genomics and proteomics in the field of nephrology. Genomics has provided a vast amount of information, linking the gene activity with disease. However, proteomic technologies allow us to understand proteins and their modifications, elucidating properties of cellular behavior that may not be reflected in analysis of gene expression. The application of these innovative approaches has recently yielded the promising new urinary biomarkers for acute kidney injury and chronic kidney disease, thus providing a better insight in renal pathophysiology and establishing the basis for new therapeutic strategies. Despite significant improvements in therapeutics, the mortality and morbidity associated with acute renal failure (ARF) remain high. The lack of early markers for ARF causes an unacceptable delay in initiating therapy. These biomarker panels will probably be useful for assessing the duration and severity of ARF, and for predicting progression and adverse clinical outcomes. Kidney failure leads to the uremic syndrome characterized by accumulation of uremic toxins, which are normally cleared by the kidneys. Proteomics has gained considerable interest in this field, as a new and promising analytical approach to identify new uremic toxins. The urinary proteome as a tool for biomarker discovery is still in its early phase. A major challenge will be the integration of proteomics with genomics data and their functional interpretation in conjunction with clinical results and epidemiology.

E-cadherin expression in upper urothelial carcinoma in Balkan Endemic Nephropathy and non-endemic regions.

There is a high incidence of upper urothelial carcinoma (UUC) in regions affected by Balkan Endemic Nephropathy (BEN). The aim of this study was to compare E-cadherin expression in UUC, in regions affected by BEN, and in control rural and city populations free of BEN. Another aim was to determine the influence of some morphological parameters on the E-cadherin status. In the samples of 85 UUC patients, of whom 40 lived in BEN settlements and 45 served as control subjects, immunoreactions were performed using monoclonal anti-human E-cadherin antibody. Aberrant expression of E-cadherin was more frequent in BEN tumors than in control tumors (p<0.01). Decreased E-cadherin expression was linked to high grade and solid growth in control and BEN tumors (p<0.0001 and <0.05 versus p<0.05 and <0.05, respectively), and to the stage in control tumors (p<0.01). However, BEN low grade and low stage tumors showed aberrant expression more often than did control tumors (p<0.05 and <0.005, respectively). In control tumors, using univariate analysis, E-cadherin status was found to be influenced by grade, stage, and tumor growth (p=0.001, 0.017, 0.015, respectively). In the same group, only the grade was significant according to multistep logistic regression analysis (Wald=6.429 and p=0.011). The growth pattern had a predominant influence on E-cadherin expression in BEN tumors (p=0.005). A significant influence on normal membranous or abnormal cytoplasmic expression of E-cadherin in UUC is exerted by tumor grade, stage, growth, and metaplastic change (p=0.002, 0.048, 0.019, 0.011, respectively), but only by tumor grade in the multistep logistic regression model. These results suggest that decreased expression of E-cadherin in BEN tumors may be linked to tumor growth, while expression of E-cadherin in control tumors may be associated with tumor grade.

[Cerebellar hemangioblastomas--a study of the immunoprofile of neoplastic stromal component]. / Hemangioblastomi malog mozga--ispitivanje imunoprofila neoplasticne strmalne komponente.

BACKGROUND: Central nervous system hemangioblastomas (HBs) are uncommon, highly vascularized tumors that are predominantly found in the cerebellum. They occur sporadically or in association with von Hippel-Lindau (VHL) disease. HBs are of unknown histogenesis, and the origin of stromal cells is still a subject of debate. The aim of this study was to investigate the immunoprofile of neoplastic stromal component, and to determine whether the profile of the expression of immunomarkers used can contribute to the elucidation of the histogenesis of HBs. METHODS: A series of eight cerebellar HBs were histochemically examined for the detection of mast cells and immunohistochemically for the expression of factor VIII-related antigen (FVIII-RAg), CD34, vimentin, factor XIIIa (FXIIIa), S-100 protein, glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), neurofilaments (NF), synaptophysin, chromogranin, and somatostatin. RESULTS: Mast cells were present in all hemangioblastomas, and were particularly abundant in one tumor. Immunohistochemically, intense reactivity for vimentin and NSE in the stromal cells was constantly seen. Immunoreactivity with S-100 protein and FXIIIa was variable, but generally many HBs stromal cells were negative for these markers. However, stromal cells were uniformly negative for FVIII-RAg in all HBs investigated. They were negative for CD34, GFAP, NF, synaptophysin, chromogranin, as well as somatostatin. GFAP-positivity of the occasional stromal type cells, located only peripherally, was interpreted as "pseudopositivity". CONCLUSION: The immunoprofile of neoplastic stromal component in this study suggested a possible origin from undifferentiated multipotential mesenchymal cells. High expression of NSE (glycolytic and hypoxia-inducible enzyme) in the HBs stromal cells might be related to the loss of the VHL protein function.