Expression of transgelin in human glomerulonephritis of various etiology.

BACKGROUND/AIMS: Activation of myofibroblasts occurs during kidney injury. Genomic and proteomic studies suggest that transgelin represents a protein that may be involved in renal injury. The purpose of this study was to estimate transgelin expression in the renal tissue of patients with glomerulonephritis. METHODS: Transgelin was identified in biopsy sections of 67 patients by immunohistochemistry and immunofluorescence. Its distribution was compared to that of α-smooth muscle actin (α-SMA), a marker of myofibroblast activation in the kidney. RESULTS: Transgelin and α-SMA expression was identified within glomeruli and interstitium. In patients with IgA nephropathy and focal segmental glomerulosclerosis, glomerular expression of transgelin was higher than that of α-SMA. The extent of transgelin immunostaining was related to mesangial proliferation (p = 0.034), glomerular sclerosis (p = 0.035), interstitial fibrosis (p = 0.047) and to the clinical course (p = 0.009). Colocalization studies showed that in some areas of kidney tissue both proteins were expressed with comparable intensity, whereas in other areas expression of either transgelin or α-SMA was predominant. CONCLUSION: Strong transgelin expression was observed in renal tissue of patients with glomerulonephritis. The observed differences in the pattern of transgelin and α-SMA expression suggest that either different subpopulations of myofibroblasts exist, or that these proteins are activated at different stages of renal injury/scarring.

Skin biopsy for the diagnosis of Alport syndrome.

Alport syndrome (AS) is the most common hereditary nephritis often associated with extrarenal manifestations. It was first described by Alport on 1927. There is a primary disorder in collagen type IV which is the main component of the basement membranes. Alport syndrome is more frequently inherited as an X-linked and less commonly as an autosomal dominant or autosomal recessive trait. We describe the case of a 3-year-old boy with the X-linked variant of AS. The diagnosis was at first speculated from the child's detailed family history and was finally confirmed by a skin biopsy. Skin biopsy is an efficient and less invasive method for the X-linked variant of the AS diagnosis.

Severe acute renal failure in a 19-year-old woman following laparoscopic cholecystectomy.

A case of severe acute renal failure in a young female patient necessitating renal replacement therapy after laparoscopic cholecystectomy is described. The histology of the renal lesion assigned to the effects of laparoscopic surgery is relevant for the pathogenesis of renal complications after such procedures. This explains part of the pathogenesis of the ischemic lesions in kidney structure that increased intra-abdominal pressure can provoke. Emphasis is given on the prevention of such side effects.

The remission of nephrotic syndrome with cyclosporin treatment does not attenuate the progression of idiopathic membranous nephropathy.

BACKGROUND: Idiopathic membranous nephropathy (IMN), a common cause of nephrotic syndrome in adults, is usually treated by combination of corticosteroids with cytotoxic drugs. In cases resistant to this regimen, the use of cyclosporin A (CsA) is followed by frequent remissions of the nephrotic syndrome. AIM: The purpose of this study was to estimate the effectiveness of prednisolone and small doses of CsA as first-line treatment of nephrotic patients with IMN, in relation to the progression of the disease, based on functional and histological changes. PATIENTS AND METHODS: Sixteen patients, with nephrotic syndrome due to IMN and well-preserved renal function, were treated with prednisolone (starting dose: 0.5 mg/kg bw/day) and CsA (starting dose: 3 mg/kg bw/day) for 24 months. A repeat renal biopsy was performed after 18 months of treatment in 10 patients with remission of nephrotic syndrome, to estimate the activity of the disease and to identify any features of CsA toxicity. RESULTS: Remission of the nephrotic syndrome was observed in 14 out of 16 patients after 5 +/- 2 months of treatment. Complete remission was observed in 8 and partial remission in 6 patients (urinary protein was reduced from 6.9 +/- 3.4-0.2 +/- 0.06 g/24 h and 1.2 +/- 1.0 g/24 h, respectively, p < 0.01). The renal function was well preserved in 13 out of 16 patients over a 24-month period of treatment. Deterioration of renal function was observed in 3 patients (creatinine clearance reduced from 86 +/- 21-37 +/- 17 ml/min, p < 0.05) who had either persistent nephrotic syndrome or frequent relapses. Relapses of the nephrotic syndrome were observed in 5 of 14 patients. Repeat renal biopsies showed that glomerular sclerosis, tubulointerstitial injury, vascular hyalinosis and stage of the disease were deteriorated in most patients. Isometric vacuolization of tubular epithelial cells was observed in 2 of 10 patients. CONCLUSION: IMN nephrotic patients treated with prednisolone and low doses of cyclosporin A showed a high remission rate of nephrotic syndrome. However, progression of chronic histological lesions was found in repeat renal biopsies. This suggests that cyclosporin can frequently induce remission of nephrotic syndrome in IMN patients, but even low doses of the drug are not free of potential renal toxicity.

Food-dependent androgen and cortisol secretion by a gastric inhibitory polypeptide-receptor expressive adrenocortical adenoma leading to hirsutism and subclinical Cushing's syndrome: in vivo and in vitro studies.

Aberrant gastric inhibitory polypeptide (GIP) receptor expression in bilaterally hyperplastic adrenals or unilateral adrenal adenomas is a rare form of adrenal hyperfunction. So far, only few cases have been described. In all these cases, cortisol was the predominant steroid released in a food-dependent manner, leading to the development of non-ACTH-dependent Cushing's syndrome. In the present study, we describe a novel case of a GIP receptor-expressive adrenocortical adenomatous nodule, detected incidentally by computed tomography scanning in a 41-yr-old lady with hirsutism but no clinical signs of Cushing's syndrome, on physical examination. Hormonal investigations in morning fasting samples showed slightly elevated androgen levels, low-normal baseline cortisol, normal suppression of cortisol after dexamethasone administration, and ACTH levels that were not suppressed and did stimulate after CRH administration. The elevated urinary free cortisol excretion, in conjunction with an atypical cortisol diurnal rhythm, raised the possibility of an aberrant stimulation of cortisol production by the adrenal tumor. Further studies demonstrated food-dependent secretion of cortisol, which was abolished by prior octreotide administration. Notably, substantial amounts of adrenal androgens were also secreted after food consumption. Removal of the tumor resulted in undetectable cortisol and androgen levels that did not respond to food consumption. Histological examination of the excised tumor revealed an adrenocortical adenomatous nodule originating from the inner zona reticularis, consisting mainly of compact cells. A steroidogenic secretory pattern, indicating the concomitant release of adrenal androgens and cortisol, was also observed in vitro from tumor cells cultured in the presence of GIP. The in vitro secretory response to GIP was higher for the adrenal androgen DHEA, compared with cortisol. The expression of the GIP receptor in tumor cells, but not in the adjacent normal adrenal, was demonstrated by RT-PCR), using specific oligonucleotide probes for this receptor. In summary, we describe a patient with a GIP-expressive cortisol and androgen oversecreting adrenocortical nodule with the unusual presentation of hirsutism and not the typical clinical signs of Cushing's syndrome. It is of note that food intake in this patient provoked a substantial increase in both adrenal androgen and cortisol levels that, together with the histological appearance of this nodule, was compatible with a zona reticularis-derived tumor. Thus, aberrant expression of the GIP receptor does not exclusively involve cells of a zona fasciculata phenotype, as previously reported, but may also occur in other types of differentiated adrenocortical cells.

Renal involvement in Adamantiades-Behçet's disease. Case report and review of the literature.

A patient with Adamantiades-Behçet's disease with renal involvement is reported. This patient fulfilled the International Study Group criteria for the disease. Kidney biopsy was performed and proliferative glomerulonephritis with deposition of IgA and IgM immunoglobulins were demonstrated. Review of the literature demonstrates that renal involvement in this disease is not so rare as it was believed. Crescent formation and IgA nephropathy are infrequently observed. Treatment of renal involvement may require immunosuppressive drugs.

Prognostic significance of matrix metalloproteinases 2 and 9 in bladder cancer.

BACKGROUND: The levels of matrix metalloproteinases MMP-2 and MMP-9 (type IV collagenases), which degrade the extracellular matrix of the basement membrane, were evaluated as prognostic indicators of metastasis in urothelial carcinoma. MATERIALS AND METHODS: Quantitative gel zymography and immunohistochemistry were used and compared with clinical data at the follow-up period of 36 months. RESULTS: Zymographical analysis of the levels of MMP-9 and active MMP-2 showed a statistically significant increase with tumor grade and invasiveness. This correlation was confirmed by immunohistochemical analysis of MMP-9 expression. However, the correlation between the levels of both gelatinases with recurrence in superficial tumours or progression in invasive tumours was not statistically significant. CONCLUSION: MMPs may have an important role in the invasion mechanism of urothelial cancer and could be useful prognostic markers for patients with bladder carcinoma. The relationship between MMP-2 and MMP-9 expression and the metastatic potential of bladder carcinoma needs further evaluation in subsequent clinical studies.

Detection of microsatellite instability in sporadic cardiac myxomas.

OBJECTIVE: Microsatellite instability (MIN) is an early event in DNA repair-deficient associated diseases and reflects an elevated mutation rate in the genome of neoplastic cells. Sporadic cardiac myxomas are the most common primary heart tumours and their aetiopathology remains obscure. This study investigates the incidence of MIN in sporadic cardiac myxomas as a possible genetic mechanism of tumour pathogenesis. METHODS: Eleven surgically excised sporadic cardiac myxomas were assessed for MI using twenty-two highly polymorphic microsatellite markers, located on a wide range of chromosomal arms. DNA was extracted from myxoma tissue specimens as well as the respective normal tissue and subjected to polymerase chain reaction. RESULTS: The microsatellite analysis revealed that seven myxoma specimens (64%) exhibited MIN in at least one marker. One tumour specimen exhibited evidence of MIN in four microsatellite markers, while the most frequently affected marker was D17S855 (27%), located on chromosome 17q. DISCUSSION: We have detected a considerable incidence of MIN in sporadic cardiac myxomas indicating that decreased fidelity in DNA replication and repair is common in these tumours. To the best of our knowledge this is the first report describing MIN in sporadic cardiac myxomas, as a possible pathogenetic mechanism of these rare neoplasms.

Differentiated thyroid cancer: a retrospective analysis of 832 cases from Greece.

OBJECTIVE: To analyse the initial manifestations, pathological findings, therapy, outcome and prognostic factors in patients with papillary and follicular carcinoma. PATIENTS: 832 patients with well differentiated thyroid carcinoma managed in our department during a period of 30 years (1965-1995). Follow-up data were available for 609 patients for a mean of 5.5 years (range 1-38 years), the remainder having been lost to follow-up. RESULTS: The patients were 677 (81%) with papillary and 155 with follicular carcinoma. They were predominantly female (75%), presenting mainly with a single nodule (53%), while at the time of diagnosis 72% had intrathyroidal carcinomas (class I), 17% had nodal metastases (class II), 7% soft tissue invasion (class III) and 4% distant metastases (class IV). Fifty-five percent of the patients had a complete thyroidectomy (36% had a near total or total thyroidectomy and 19% near total or total thyroidectomy plus block dissection), 2.6% received external radiotherapy and 94% had radioactive iodine as part of the treatment of the original disease. Kaplan-Meier survival analysis was used to calculate both cancer related mortality and disease free survival in the patients followed-up. Although mortality (21 cancer-related deaths) was slightly higher for follicular than papillary carcinoma (10% vs. 5% and 16% vs. 10% in 10- and 15-year survival, respectively) the difference was not statistically significant. Extent of disease at diagnosis, male sex, tumour size and age > 60 years affected probability of cancer death. Cox's proportional hazard regression analysis for disease free survival showed that adverse independent prognostic factors were, for papillary carcinoma, male sex, class II or higher, tumour size > 1 cm and age > 60 years, while for follicular, class III or higher, size > 4 cm and age > 40 years. CONCLUSIONS: We conclude that there is a higher prevalence of follicular carcinoma in our country probably due to a moderate degree of iodine deficiency still existing in Greece. Age and extent of disease at diagnosis were important prognostic factors affecting morbidity and mortality, whereas sex, tumour features and histological type were of minor importance. All these prognostic factors and their relative importance should be taken in consideration in the management of this disease.

Acute onset of dermatomyositis presenting in pregnancy with rhabdomyolysis and fetal loss.

We report a case of acute onset of dermatomyositis with rhabdomyolysis and myoglobinuria, which presented in the 14th week of pregnancy and resulted in spontaneous abortion of the fetus. The diagnostic work up for an underlying disease was negative and the histologic examination confirmed the diagnosis of dermatomyositis, which subsequently improved with corticosteroids.

A case of systemic karyomegaly associated with interstitial nephritis.

A case of systemic karyomegaly is described for the first time in Greece. This rare disease entity was first described in 1979 by Mihatsh and so far only nine cases have been reported. Typical clinical features are progressive renal failure in the third decade of life and recurrent infections, mostly of the upper respiratory tract. Typical histologic findings are markedly enlarged and hyperchromic nuclei in tubular cells of the nephron and interstitial fibrosis surrounding the atrophic tubules.

Immunohistochemical detection of bcl2, p53, mdm2 and p21/waf1 proteins in small-cell lung carcinomas.

Thirty-one cases of small cell lung carcinomas (SCLC) were investigated by immunohistochemistry for the expression of bcl-2. P53 and the wild-type (wt) p53-induced proteins mdm2 and p21/waf1. Bcl-2 protein was detected in 24/31 cases of SCLC(77%) and p53 protein in 13/31 cases (42%). No correlation was found between histological subtype of SCLC and bcl-2 or p53 expression. Comparison between bcl-2 and p53 expression showed that 14/31 cases (45%) were only bcl-2 positive, 3/31 (11%) were only p53 positive, 10/31 (32%) were positive for both proteins and 4/31 (13%) were negative for both proteins. Mdm2 protein was detected in 2/32 SCLC which were also p53 positive. P21 protein was detected in 6/32 SCLC. Four of the p21 positive SCLC were negative for both p53 and mdm2, and two were positive for both p53 and mdm2 proteins. The significant expression of bcl-2 protein in SCLC suggests that bcl-2 may be involved in the pathogenesis of most SCLC by inhibiting apoptosis during neoplastic transformation. The expression of p53 protein in SCLC is likely to be related to underlying p53 gene mutations since these genetic alterations are very frequent in SCLC. This can be supported by our findings that 11/13 p53 positive SCLC were mdm2 and p21 negative. The two cases with p53+/mdm2+/p21+ phenotype may represent tumours with wt p53 gene and p53 protein immunoexpression due to binding to mdm2 protein. The four cases with p53-/mdm2-/p21+ phenotype may represent tumours with p53-independent p21 protein expression. Coexpression of p53 and bcl-2 proteins in a proportion of SCLC suggests that in these tumours p53 does not maintain its suppressive effect on bcl-2 expression as has been reported in vitro. Further studies at the DNA and RNA level are required to clarify the involvement of bcl-2, p53, mdm2 and wafl genes in SCLC pathogenesis.

Immunohistochemical detection of bcl2, p53, mdm2 and p21/waf1 proteins in small-cell lung carcinomas.

Thirty-one cases of small cell lung carcinomas (SCLC) were investigated by immunohistochemistry for the expression of bcl-2, p53 and the wild-type (wt) p53- induced proteins mdm2 and p21/waf1. Bcl-2 protein was detected in 24/31 cases of SCLC(77%) and p53 protein in 13/31 cases (42%). No correlation was found between histological subtype of SCLC and bcl-2 or p53 expression. Comparison between bcl-2 and p53 expression showed that 14/31 cases (45%) were only bcl-2 positive, 3/31 (11%) were only p53 positive, 10/31 (32%) were positive for both proteins and 4/31 (13%) were negative for both proteins. Mdm2 protein was detected in 2/32 SCLC which were also p53 positive. P21 protein was detected in 6/32 SCLC. Four of the p21 positive SCLC were negative for both p53 and mdm2, and two were positive for both p53 and mdm2 proteins. The significant expression of bcl-2 protein in SCLC suggests that bcl-2 may be involved in the pathogenesis of most SCLC by inhibiting apoptosis during neoplastic transformation. The expression of p53 protein in SCLC is likely to be related to underlying p53 gene mutations since these genetic alterations are very frequent in SCLC. This can be supported by our findings that 11/13 p53 positive SCLC were mdm2 and p21 negative. The two cases with p53+/mdm2+/p21+ phenotype may represent tumours with wt p53 gene and p53 protein immunoexpression due to binding to mdm2 protein. The four cases with p53-/mdm2-/p21+ phenotype may represent tumours with p53-independent p21 protein expression. Coexpression of p53 and bcl-2 proteins in a proportion of SCLC suggests that in these tumours p53 doses not maintain its suppressive effect on bcl-2 expression as it has been reported in vitro. Further studies at DNA and RNA level are required to clarify the involvement of bcl-2, p53, mdm2 and waf1 genes in SCLC pathogenesis.

Expression of p53, mdm2, p21/waf1 and bcl-2 proteins in thymomas.

We have investigated the immunohistochemical expression of p53, mdm2, p21/waf1 and bcl-2 proteins in 31 thymic epithelial tumours comprising five medullary thymomas (MDT), four mixed thymomas (MT), 12 cortical thymomas (CT), eight predominately cortical thymomas (PCT) and two well-differentiated thymic carcinomas (WDTC). We have found p53, mdm2, p21 and bcl-2 protein expression in 25/31, 8/31, 5/31 and 10/31 thymic epithelial tumours, respectively. Coexpression of p53 and mdm2 proteins was found in eight cases (three CT, four PCT and one WDTC). Five of them were also p21 positive and three p21 negative. Discordant p53+/mdm2-/p21- protein expression was found in 19 cases (three MDT, three MT, nine CT, three PCT and one WDTC). Mdm2 and p21 proteins were not expressed in the absence of p53 protein. Coexpression of bcl-2 and p53 proteins was found in seven cases (three MDT, three MT and one WDTC). Eighteen cases were p53+/bcl-2- (10 CT, seven PCT and one WDTC) and three cases (two MDT and one MT) were bcl-2+/p53-. Our findings indicate that in thymomas, p53 expression is more frequently associated with cortical histotypes while bcl-2 expression is strongly associated with medullary and mixed histotypes. In addition, there is an inverse correlation between p53 and bcl-2 protein expression in thymomas. Coexpression of p53/mdm2/p21 proteins may reflect thymomas with wild-type (wt), p53 gene since mdm2 and p21 proteins are inducible by wt p53 gene. However, in view of previous findings that p53 mutation is an early event in thymomas, the possibility of p53 gene mutation with p53-independent mdm2 and p21 expression should be considered in these cases. Discordant p53+/mdm2-/p21- protein expression may represent thymomas with p53 gene mutations unable to activate expression of mdm2 and p21 proteins.

Expression of bcl-2 and p53 proteins in nasopharyngeal carcinoma. Absence of correlation with the presence of EBV encoded EBER1-2 transcripts and latent membrane protein-1.

Aims-To investigate the immunohistochemical expression of bcl-2 and p53 proteins in nasopharyngeal carcinomas in relation to the expression of the Epstein-Barr virus (EBV) encoded EBER messenger RNAs (mRNAs) and latent membrane protein-1 (LMP-1).Methods-Formalin fixed, paraffin wax embedded tissue from 44 nasopharyngeal carcinomas (NPCs) was stained by immunohistochemistry for p53, bcl-2 and LMP-1 proteins and by RNA in situ hybridisation for EBER mRNAs.Results-The tumours were divided histologically into 13 cases of keratinising squamous cell NPC (KNPC), 15 cases of non-keratinising squamous cell NPC (NKNPC) and 16 cases of undifferentiated NPC (UNPC). Bcl-2 expression was observed in five of 15 NKNPC cases and in six of 16 UNPC cases; p53 expression was observed in one of 13 KNPC, two of 15 NKNPC and four of 16 UNPC cases. EBER 1-2 transcripts were detected in five of 15 NKNPC and nine of 16 UNPC cases, while LMP-1 expression was observed in one of 16 UNPC cases. All 13 KNPCs were EBV and bcl-2 negative. No correlation was found between the presence of EBER 1-2 transcripts and the detection of bcl-2 or p53 proteins, or both, in NPC cells.Conclusions-The expression of bcl-2 and p53 proteins may be associated with the level of the tumour cell differentiation in NPC. In addition, in view of the important role of the bcl-2 protein in the inhibition of apoptosis, the expression of bcl-2 protein may contribute to tumour cell survival in a proportion of NPCs. Furthermore, in the light of previous findings that the p53 gene in most UNPCs is in the wild-type configuration, mechanisms other than mutation may be responsible for stabilisation of the p53 protein in UNPCs.

[Isolated amyloidosis of the ureter. Apropos of a case and review of the literature]. / Amylose isolée de l'uretère. A propos d'un cas et revue de la littérature.

Stenosis of the mid-portion of the right ureter and moderate hydronephrosis of the right kidney was seen on the intravenous pyelography of a 60-year-old patient consulting for sudden onset pain in the right inguinal region. Confirmation was obtained with retrograde urography and abdominal computed tomography. Right nephroureterectomy was performed. The pathology examination revealed characteristic features of amylosis located solely at the narrowing of the ureter. Isolated amylosis of the ureter is rare and difficult to diagnose.

No correlation between ras, c-myc and c-jun proto-oncogene expression and prognosis in advanced carcinoma of cervix.

55 patients suffering from stage III or IV carcinoma of cervix were treated with two pulses of neo-adjuvant chemotherapy prior to radical radiotherapy. 51% (26/51) had a partial response. The initial response to chemotherapy is associated with significantly better long-term survival. The 3-year survival of chemotherapy responders is 62% against 21% for non-responders (P = 0.009 log-rank test). To detect possible differences in oncogene expression in biopsy specimens taken from responding and non-responding patients, paraffin-fixed material was immunocytochemically stained for the expression of the protein products of ras, c-myc and c-jun proto-oncogenes. The frequency of oncogene expression was ras 80.4%, c-myc 45.1% and c-jun 39.2%. There was no statistically significant association between oncogene expression, time to local recurrence or development of metastases or survival.

Expression of ras p21 and myc p62 oncoproteins in small cell and non small cell carcinoma of the lung.

Ras p21 and myc p62 expression has been examined immunohistochemically in seventy specimens of bronchial carcinomas. Both ras and myc oncoproteins were found to be overexpressed at a higher frequency in non small cell carcinomas (squamous cell carcinomas and adenocarcinomas) compared to the small cell carcinoma specimens; however only myc p62 overexpression was found to be statistically significant. Also, ras p21 oncoprotein expression was frequently overexpressed in adenocarcinomas compared to squamous cell carcinomas (p less than 0.05). Overexpression of c-myc p62 was found to correlate with poorly differentiated squamous cell carcinomas compared to the well and moderately differentiated tumors. The results of this study indicate that both the ras and myc oncogenes are important in the progression of bronchial carcinomas.