Fractal analysis of two-dimensional vascularity in primary prostate cancer and surrounding non-tumoral parenchyma.

Prostate cancer is the fifth most frequent cancer in the world. However, none of the actual prognostic factors provide a valid index for predicting patient outcome. Here, we evaluate the two-dimensional vascularity in primary prostate tumors and surrounding non-tumoral parenchyma by means of fractal geometry, and assess any correlations between the results and some clinical and pathological parameters of prostate carcinoma. Prostate sections from 27 carcinoma patients were treated with CD34 antibodies. Two >10mm(2) areas of tumoral and surrounding non-tumoral parenchyma were digitized using an image analysis system that automatically quantified the fractal dimension of the vascular surface. Data were correlated with patient's age, PSA level, clinical and pathological stage, Gleason score, tumor volume, vascular invasion, surgical margins, and biochemical relapse. Two groups of patients were distinguished on the basis of whether the fractal dimension of their tumoral vascular surface was higher (group 1) or lower (group 2) than that of the surrounding non-tumoral parenchyma. Statistically significant between-group differences were found in terms of serum PSA levels (p=0.0061), tumor volume (p=0.0017), and biochemical relapse (p=0.031). The patients in group 2 had a poorer outcome. Our findings suggest a group of prostate cancer patients with a poor outcome, and the vascular surface fractal dimension as a helpful geometrical index in clinical practice.

Fractal dimension as a quantitator of the microvasculature of normal and adenomatous pituitary tissue.

It is well known that angiogenesis is a complex process that accompanies neoplastic growth, but pituitary tumours are less vascularized than normal pituitary glands. Several analytical methods aimed at quantifying the vascular system in two-dimensional histological sections have been proposed, with very discordant results. In this study we investigated the non-Euclidean geometrical complexity of the two-dimensional microvasculature of normal pituitary glands and pituitary adenomas by quantifying the surface fractal dimension that measures its space-filling property. We found a statistical significant difference between the mean vascular surface fractal dimension estimated in normal versus adenomatous tissues (P = 0.01), normal versus secreting adenomatous tissues (P = 0.0003), and normal versus non-secreting adenomatous tissues (P = 0.047), whereas the difference between the secreting and non-secreting adenomatous tissues was not statistically significant. This study provides the first demonstration that fractal dimension is an objective and valid quantitator of the two-dimensional geometrical complexity of the pituitary gland microvascular network in physiological and pathological states. Further studies are needed to compare the vascular surface fractal dimension estimates in different subtypes of pituitary tumours and correlate them with clinical parameters in order to evaluate whether the distribution pattern of vascular growth is related to a particular state of the pituitary gland.

The complex functions of mast cells in chronic human liver diseases.

Mast cells (MCs) are multifunctional effector cells of the immune system. MCs were originally thought to be involved in IgE-associated immediate hypersensitivity and allergic disorders, but it is now known that they contain or elaborate an array of mediators with a multitude of effects on many other cells. A number of studies have found that MCs are involved in various liver diseases. Although still controversial, they seem to be involved in the liver's fibrotic response to chronic inflammation and parasitic infection. Hepatic fibrosis is the most frequent liver response to toxic, infectious, or metabolic agents. During the establishment of this pathological condition, there is an increase in the components of the basement membrane that leads to continuous basement membrane-like structures being raised within Disse's space and a decrease in the number of sinusoid endothelial fenestrae. This leads to a complex process called "sinusoidal capillarization." At the cellular level, liver fibrogenesis is initiated by hepatocyte necrosis, which induces the recruitment of a large number of inflammatory cells, including MCs, which can be considered the primary effectors of the process changing sinusoidal endothelial cells into capillary-type endothelial cells. We review the roles played by MCs in hepatic chronic diseases and describe a biopsy section of hepatic tissue taken from a patient with chronic C virus-related hepatitis showing diffuse sinusoidal capillarization and a high density of MCs. This observation has led us to hypothesize a relationship between these highly specialized cells and sinusoidal capillarization.

Early cytotoxic effects of ochratoxin A in rat liver: a morphological, biochemical and molecular study.

We characterized the overall early effect of chronic ochratoxin A (OTA) treatment on rat liver, analyzing different aspects related to: (i) fibrosis, by measuring collagen content and turnover, and alpha-smooth muscle actin (alphaSMA); (ii) oxidative stress and stress response, by analyzing protein carbonylation, superoxide dismutase (SOD) and heat shock protein (HSP70) gene expression; (iii) the possible tumor promoter effect, evaluating cadherin and connexin (CX) mRNA levels. Light microscopy analysis showed no histological differences in OTA-treated and control (CT) rats. Collagen content, determined by computer analysis of Sirius red-stained liver sections, was similar in both groups. In liver homogenates COL-I, COL-III, TIMP-1 and TGF-beta1 mRNA levels and alphaSMA were unaffected by OTA. Matrix metalloproteinase (MMP)-1, MMP-2 and MMP-9 protein levels were also similar in the two groups. Protein carbonylation, a marker of severe oxidative stress, was not evident in the homogenates of OTA-treated livers; superoxide dismutase (SOD) mRNA tended to be lower and HSP70 was strongly down-regulated. OTA reduced E-cadherin and DSC-2 transcription, and down-regulated liver CX26, CX32 and CX43. In conclusion, these in vivo results show that OTA-induced liver injury involves a reduction in the ability to counterbalance oxidative stress, maybe leading to altered gap junction intercellular communication and loss of cell adhesion and polarity. This suggests that mild oxidative damage might be a key factor, in combination with other cytotoxic effects, in triggering the promotion of liver tumors after exposure to OTA.

Sperm protein 17 is expressed in human nervous system tumours.

BACKGROUND: Human sperm protein 17 (Sp17) is a highly conserved protein that was originally isolated from a rabbit epididymal sperm membrane and testis membrane pellet. It has recently been included in the cancer/testis (CT) antigen family, and shown to be expressed in multiple myeloma and ovarian cancer. We investigated its immunolocalisation in specimens of nervous system (NS) malignancies, in order to establish its usefulness as a target for tumour-vaccine strategies. METHODS: The expression of Sp17 was assessed by means of a standardised immunohistochemical procedure [(mAb/antigen) MF1/Sp17] in formalin-fixed and paraffin embedded surgical specimens of NS malignancies, including 28 neuroectodermal primary tumours (6 astrocytomas, 16 glioblastoma multiforme, 5 oligodendrogliomas, and 1 ependymoma), 25 meningeal tumours, and five peripheral nerve sheath tumours (4 schwannomas, and 1 neurofibroma). RESULTS: A number of neuroectodermal (21%) and meningeal tumours (4%) were found heterogeneously immunopositive for Sp17. None of the peripheral nerve sheath tumours was immunopositive for Sp17. The expression pattern was heterogeneous in all of the positive samples, and did not correlate with the degree of malignancy. CONCLUSION: The frequency of expression and non-uniform cell distribution of Sp17 suggest that it cannot be used as a unique immunotherapeutic target in NS cancer. However, our results do show the immunolocalisation of Sp17 in a proportion of NS tumour cells, but not in their non-pathological counterparts. The emerging complex function of Sp17 makes further studies necessary to clarify the link between it and immunopositive cells.

Sperm protein 17 expression defines 2 subsets of primary esthesioneuroblastoma.

Esthesioneuroblastomas (ENBs) are rare malignant tumors of the nasal vault, the origin, diagnosis, and management of which are still subjects of discussion. That there is no related prognostic factor or generally recognized therapeutic regimen highlights the need for further analyses of its underlying biologic features and investigations of new marker proteins that allow more reliable clinical testing. We here show that sperm protein 17 (Sp17) is expressed in the ciliated cells of the normal olfactory epithelium and in a proportion of primary ENB lesions. We found an association between Sp17 expression and metastases at relapse (P = .035), chromogranin expression (P = .014), and a female sex prevalence. A statistically nonsignificant relation was found between Sp17 and S-100, synaptophysin, and neurofilament expression. No correlation was also found between Sp17 expression and the proliferative capacity of the lesion that was evaluated by Ki-67 immunohistochemistry. The results of this study show the usefulness of Sp17 as a means of discriminating 2 subsets of primary ENB lesions and seem to suggest the existence of 2 distinct cell pathways in their origin and development.