Prognostic significance of augmented metallothionein (MT) expression correlated with Ki-67 antigen expression in selected soft tissue sarcomas.

In soft tissue sarcomas, the most important prognostic criteria include extent of malignancy (G), size of the tumour and intensity of Ki-67 antigen expression. In recent times expression of metallothionein (MT) in cells of some malignant processes of epithelial origin was found to correlate with intensity of Ki-67 antigen expression and to carry a possible prognostic significance. The present study aimed at a demonstration of prognostic value of MT expression and at comparing it with Ki-67 antigen expression and G grade in selected soft tissue sarcomas. Immunohistochemical studies were performed on paraffin sections in 54 cases of malignant fibrous histiocytoma (MFH), 18 cases of liposarcoma and 20 cases of synovial sarcoma. The extent of MT and Ki-67 antigen expression was evaluated and an attempt was made to correlate the results with each other and with grade of the tumour. Expression of MT was evident both in the cytoplasm and in cell nuclei of all studied sarcomas. The most pronounced MT expression was noted in MFH-type tumours. The extent of Ki-67 antigen expression was similar in MFH and liposarcoma and was the lowest in synovial sarcoma. In MFH, liposarcoma and synovial sarcoma a pronounced positive correlation was documented between expression of MT and Ki-67 antigen (r=0.85; p<0.001; r=0.93, p<0.0001; r=0.79, p<0.0001). In all types of the tumours a positive relation was detected between MT expression, expression of Ki-67 and G grade of malignancy in the tumour. Moreover, patients with higher MT expression in the studied tumours demonstrated a shorter survival. MT expression in soft tissue tumours of MFH, liposarcoma and synovial sarcoma type strongly correlated with intensity of proliferation (Ki-67) and G grade and could be useful in defining the extent of malignancy and in prognostic appraisal in the tumours.

The application of electron microscopic morphometry as a helpful method in the diagnosis of focal segmental glomerulosclerosis (FSGS) early phase. II. Clinical usefulness of electron microscopic morphometric studies in cases of minimal change disease (MCD) and mesangioproliferative glomerulonephritis (GNMES) with suspicion of progression into focal segmental glomerulosclerosis (FSGS).

Clinical and morphological analysis (including morphometric studies of electron microscopic material) was made in 15 children with MCD and 15 children with GNMES. In both groups, an early phase of FSGS was suspected on the basis of electron microscopic studies. Moreover, analysis included the results obtained in 13 children with the diagnosis of FSGS and in whom repeated biopsies were performed. In most of them, MCD or GNMES was diagnosed from the first biopsy. In most children in whom electron microscopic studies revealed an increase in matrix area in some mesangial regions, thereby suggesting an early stage of glomerular sclerosis, the results of morphometric studies resembled or were identical to the results obtained from a control group with the established diagnosis of FSGS. These findings indicate that morphometric studies of electron microscopic material are significant. The results, when compared with the clinical data, confirm the usefulness of such a diagnostic procedure.

Immunocytochemical localisation of PTHrP (parathormone-related peptide) in myoepithelial cells of human sweat and parotid glands.

PTHrP is a HHM-inducing peptide. It exhibits certain structural similarity to PTH and the two hormones may act through the same receptors. PTHrP is known to be produced in various tissues as well as during development. In this study we decided to immunocytochemically demonstrate PTHrP in normal skin and squamous cell carcinomas as well as in parotid glands (normal, inflamed and neoplastic). In the skin, PTHrP expression was demonstrated in epidermis and in smooth muscle cell layer of blood vessels. In squamous cell carcinomas, the expression was noted in foci of keratinization. In parotid glands, the peptide was localised in excretory ducts and in blood vessels, while inflammation of the gland and its tumours resulted most frequently in the less intense immunoreaction. The results are consistent with those of other authors. The novel observations include demonstration of PTHrP expression in myoepithelial cells of sweat glands and in parotid glands, where it may be involved in the control of their contractile activity.

[Comparative study of two immunosuppressive treatment methods in patients with focal segmental glomerulosclerosis]. / Porównanie dwóch metod leczenia immunosupresyjnego u chorych na ogniskowa segmentalna sklerotyzacje klebuszków nerkowych.

Focal segmental glomerulosclerosis (FSGS) is a glomerular disease of varying severity. Most patients, however, develop end-stage renal failure within 10 years from clinical onset. In this retrospective study, the outcome of immunosuppressive treatment in 22 adult patients with biopsy-proven primary FSGS was evaluated. Eleven patients were treated with prednisone, azathioprine and chlorambucil (group A) and 11 with prednisone and pulse cyclophosphamide (group B). The nephrotic syndrome (NS) was found in 4 patients from the group A and in 3 patients from the group B, arterial hypertension in 8 and 9 patients, respectively. During the follow-up lasting about 50 months as the mean, 70% of the patients did not respond to the treatment and complete remission was obtained only in 3 patients from the group B. On the other hand, 7 patients progressed into CFR. Among them, 5 out of 7 patients with NS (4 from the group A) needed dialysis treatment or doubled their Pcr after a mean of 38 months. This study confirms poor outcome of immunosuppressive treatment in patients with FSGS. However, of the two forms of treatment used in the study, the response appeared to be better and more lasting with cyclophosphamide than with azathioprine and chlorambucil. Corticosteroids associated with pulse cyclophosphamide therapy seems to improve the chances of remission and to protect from renal dysfunction.

Is vacuolization of podocytes and glomerular endothelial cells of prognostic value with respect to FSGS?

Focal segmental glomerulosclerosis (FSGS) poses a major problem both from the clinical and pathomorphological viewpoint. The diagnosis of FSGS in its early stage is vital mainly because of rapidly developing therapeutic modalities. In the literature various changes are discussed which may be of prognostic value (may predict the development of FSGS). One the these changes in vacuolization, mainly of podocytes and less frequently of endothelial cells. The purpose of the present study was to analyse biopsy specimens to find out to what extent vacuolization of podocytes and endothelial cells is associated with FSGS. We compared vacuolization in minimal change disease (MCD), mesangial glomerulonephritis (GNMES) and FSGS. A similar analysis was made also with respect to those cases of MCD and GNMES, in which electron microscopy suggested an early stage of FSGS. In each group electron micrographs obtained from 15 children were analysed. Electron micrographs (12-15 on average) were obtained most frequently from 3 glomeruli. Each case electron micrographs contained 90-100 podocytes. Based upon the same electron micrographs we counted capillary lumina and defined the percentage of those which contained vacuolized endothelia (we counted the capillary lumina, and not the cells, because it is most frequently impossible to identify the border of vacuolized endothelial cells). The number of capillary cross-sections was 60 on average. The results of the analysis were compared with the clinical data. This comparison did not confirm the hypothesis of other investigators that vacuolization is of a prognostic value. Additionally we evaluated the character of vacuoles. Within podocytes the vacuoles were varying in shape. Surrounded by a single membranous layer most frequently they contained material corresponding to proteins or proteoglycans, rarely to lipids. Sometimes the vacuoles were autophagosomal, occasionally they consisted of the dilated rough endoplasmic reticulum. Vacuole-like changes within the capillary lumina were related to the swelling of endothelial cytoplasm or mesangial processes. The reasons for a discrepancy between our results and those reported by other investigators necessitate further studies.

Mesangial glomerulonephritis (GNMes) in children. Diagnostic problems, usefulness of repeated biopsy.

We analysed the results of clinical and morphological examinations in 256 children with mesangial glomerulonephritis. In the majority of children the onset of the disease was associated with the nephrotic syndrome, less frequently with erythrocyturia, proteinuria plus erythrocyturia or proteinuria. The course of the disease was markedly worse in those with proteinuria. The patients in this group were most frequently submitted for repeated biopsy. Renal specimens were studied in light, electron and immunofluorescence microscopy. Certain relationships between the initial symptoms and composition of deposits were found. There was, however no relation between the presence or absence of the deposits or their composition and the course of the disease. In 30 children the results of first biopsy (mainly electron microscopy examinations) suggested a possibility of focal segmental glomerulosclerosis (FSG). In 11 out of these children biopsy was repeated confirming the results of the first one. Repeated biopsy was performed in a total of 22 children. Progression of changes (signs of FSG) was found in 19 children, in 2 children changes in repeated biopsy did not differ from those in first biopsy, and in one child regression was observed.

Morphometric analysis in the diagnosis and differentiation of certain glomerulopathies (MCD, GNMes, FSG)

Morphometric analysis was used to evaluate mesangial components in MCD (minimal changes disease), GNMes (mesangial glomerulonephritis), FSG (focal segmental glomerulosclerosis). In GNMes the increase of matrix was found to be generally proportional to the amount of mesangial cells. There are clear statistically significant differences in the ratio of matrix volume to cell component volume and of matrix volume to the whole mesangial area in MCD and GNMes as compared with FSG. In the case of GNMes where morphometric results resemble those in FSG cautious prognosis is recommended as there is a possibility of FSG. This has been confirmed both by the course of the disease and the results of repeated biopsy.

The clinicomorphological correlations in Schoenlein-Henoch nephropathy in children.

Clinicomorphological analysis has been performed in Schoenlein-Henoch nephropathy. Various clinical symptoms are accompanied by morphological changes of variable type and severity. Electron microscopy is a major tool for evaluating these changes. It relatively frequently modifies the diagnosis made by light microscopy. It mainly concerns class I and VI changes (according to a grading system of the International Study Group of Kidney Diseases in Childhood). It was shown that late prognosis was largely determined by the type and severity of morphological changes. Varying severity of changes in individual glomeruli in the same specimen requires in each case a comparison of results obtained by electron microscopy with those obtained by light microscopy in semithin sections. In three children biopsy was repeated. Progression of morphological changes was found in one child. He developed renal failure. In one child morphological changes on first biopsy did not differ from those on second biopsy. Repeated biopsy was performed due to the presence of hypertension. In one child with persistent proteinuria repeated biopsy showed marked attenuation of morphological changes.

Focal segmental glomerulosclerosis in children.

Clinical and morphological examinations in 25 children with the diagnosis of focal segmental glomerulosclerosis (FSG) show that: 1. electron microscopy permits a detection of FSG in its early stage when light microscopy does not reveal any changes, and immunomorphological studies do not show deposits 2. in this stage small focal interstitial changes may be visible 3. ultrastructural studies reveal changes in case of nonspecific light microscopy i.e. suggesting mesangial glomerulonephritis 4. in doubtful cases it is useful to repeat biopsy.