Expression of E-cadherin, ß-catenin, and epithelial membrane antigen does not predict survival in patients with high-risk non-muscle-invasive bladder cancer.

THE AIM OF THE STUDY: The aim of the study was to validate the value of E-cadherin and ß-catenin expression and to test an alternative prognostic marker, epithelial membrane antigen (EMA). MATERIAL AND METHODS: Forty-nine consecutive patients with primary stage T1 non-muscle-invasive bladder cancer (NMIBC) were enrolled in this study. Tissue specimens were stained with the following mouse anti-human antibodies: anti-E-cadherin, anti-ß-catenin, and anti-EMA. Reaction intensity within cancer cells was assessed according to the immunoreactive score (IRS). Finally, the association between the expression of selected proteins and patient survival was assessed. RESULTS: The mean follow-up was 34.8 months. Recurrence-free survival, progression-free survival, and overall survival (OS) were 47.5%, 72.5%, and 72.5%, respectively. Differences in the IRS for ß-catenin and EMA were found clinically, but were not statistically significant in prediction of the risk of disease progression (p > 0.05). No difference in protein expression was observed regarding the risk of recurrence, OS, or cancer-specific mortality (p > 0.05). Stratification of patients based on the IRS into three groups (poor, moderate, and intensive reaction) failed to identify a prognostic marker among the tested proteins (p > 0.05). CONCLUSIONS: Expression of E-cadherin, ß-catenin, and EMA cannot reliably predict survival in patients with high-risk NMIBC. Further searches are needed to identify tissue markers of progression and recurrence in NMIBC.

Immunohistochemical differentiation between muscularis mucosae and muscularis propria for improving the staging of bladder cancer in patients undergoing transurethral resection of bladder tumours.

Microscopic differentiation between muscularis mucosae (MM) and muscularis propria (MP) of the bladder in the material obtained during transurethral resection (TUR) remains difficult. The study was aimed at determination of the usefulness of immunohistochemical staining in this context. Forty-seven TUR specimens were stained with 5 mouse anti-human antibodies: anti-desmin, anti-filamin, anti-type IV collagen, anti-smoothelin, and anti-vimentin. Slides were assessed under light microscopy and the intensity of the immune reaction within MM and MP was evaluated on a four-level visual scale as follows: negative (0) and weakly (1), moderately (2), or strongly (3) positive. MM was identified in 27 patients (57.4%). The modal values of reaction intensity in MM and MP was 0 and 2 for desmin (p > 0.05), 2 and 2 for filamin (p = 0.01), 2 and 2 for type IV collagen (p > 0.05), 1 and 2 for smoothelin (p = 0.03), and 2 and 0 for vimentin (p = 0.02), respectively. Identical intensity within MM and MP was observed in 7.1%, 28.6%, 20%, 30.1%, 5.6%, respectively. Immunohistochemistry can help differentiate between MM and MP in TUR specimens. As of yet, no single marker can reliably differentiate between MM and MP; however, a combination of anti-filamin, anti-smoothelin, and anti-vimentin antibodies may be reasonable for diagnostic purposes.

Possible role of complement factors and their inhibitors in the myocardial infarction: an immunohistochemical study.

Ongoing development of our civilization is accompanied by a marked increase of incidence of cardiovascular diseases and cardiovascular mortality. Ischemic heart disease with its extreme form - myocardial infarction - is one of the main problems of modern medicine. Despite much research devoted to this disease entity, its pathomechanism remains incompletely understood. Basing on research reports, more and more emphasis is put on immune reactions in the myocardium. Available literature lacks detailed studies examining the role of complement system and its inhibitors in the development and pathogenesis of myocardial infarction. Cells of ischemic myocardium were proven to become foreign antigens for the immune system of the patient's body. This results in complement activation of formation of so called membrane attacking complex that injures myocardial cells. By binding to its surface, it extends the myocardial destruction caused by the infarction itself. Results of immunochemistry studies presented in this paper have demonstrated the existence colocalization of complement components (C4d, C9) and membrane inhibitors (CD55, CD59) as well as soluble inhibitors (factor H) of the complement in the examined muscle tissue that underwent ischemic necrosis. Positive immunohistochemical reaction was found in the myocardial cells, intercellular matrix and blood vessels.

Spontaneous regression of renal cell carcinoma.

Renal cell carcinoma (RCC) comprises 3-4% of all malignant tumours among adults in Poland. Spontaneous regression of RCC is a rare but well-known phenomenon. Its frequency is estimated to be approximately 1% and a large part of the percentage is accounted for by the regression of pulmonary metastases in the course of clear type of RCC treatment. We searched PubMed, Embase and SciVerse Scopus databases, identifying 59 case reports of spontaneous regression of RCC. Those medical histories come from reports from around the world and date back up to 40 years. This review includes their analysis as well as description of possible explanations of this phenomenon postulated by different authors, including both misdiagnosis and immunological reactions. This study indicates that reliable diagnostics and reporting of all the cases of spontaneous regression play a key role, as this is the only method which enables a better perspective in understanding this issue.

The possible role of factor H in colon cancer resistance to complement attack.

A soluble complement inhibitor factor H (FH) and its splice variant factor H-like protein (FHL) have been recently discovered to play a major role in malignant cell escape from complement-mediated cytotoxicity in lung-, ovarian- and glia-derived neoplasms. The role of FH in colon cancer has not yet been examined. Here, we studied immunocytochemically FH/FHL expression in tumor samples derived from 40 patients, with both primary colon adenocarcinoma and metastatic foci in the liver. FH/FHL immunoreactivity was present in stroma of both primary and metastatic tumors, in virtually all patients. The cellular immunoreactivity was observed infrequently. Importantly, when analyzed quantitatively, FH/FHL immunoreactivity was significantly increased in liver metastases when compared with the primary sites. In addition, we have analyzed FH and FHL expression in 5 colon cancer cell lines: SW480, SW620, HCT116, HT-29 and Lovo. FH mRNA and FH secretion were observed in SW620 and HT-29 cells, whereas FHL was produced only by HT-29 cell-line. By confocal and electron microscopy, FH immunoreactivity was associated with the plasma membrane and intracellular vesicular structures. Finally, we have analyzed the role of FH in the susceptibility of SW620 colon cancer cells to complement-mediated damage. When FH function was blocked, using specific antibody, the cells became more susceptible to lysis. Taken together, our results suggest an important role of FH/FHL in colon cancer cells defense against complement-mediated cytotoxicity, and in metastatic process.

Morphological features and differential diagnosis of hepatitis C recurrence after liver transplantation - literature review and results of single transplantation center.

Orthotopic liver transplantation (OLT) is an established method of treatment for advanced and irreversible liver diseases. Type C (HCV) viral hepatitis is the most common indication for OLT in Western Europe, USA, and also in Poland. Recurrence of primary disease, that led to OLT, constitutes the crucial problem in medical care of transplanted patients. HCV recurrence is nearly universal, but the course of reinfection is unpredictable. There are many risk factors predisposing to more severe liver disease, related to characteristics of donor, recipient and virus. It was noted, that the course of HCV reinfection was more aggressive in patients transplanted in recent years. Generally, chronic HCV infection develops more aggressively in the liver allograft compared to the native liver and leads more rapidly to liver cirrhosis and graft failure. There are no certain laboratory tests or imaging techniques reflecting the status of infected liver. Morphological examination of liver biopsies is still essential to assess actual organ status, the activity and progression of the inflammatory process and the presence of other posttransplant complications. Results concerning the course of HCV reinfection are equivocal and differ in various populations. Many unresolved issues still remain. In the presented study pathomorphological features of HCV reinfection, differential diagnosis, and the basic results of authors' investigations concerning the relationship between many clinical and histopathological data and aggressiveness of HCV reinfection are described.

Heart infarct as the major cause of death of hematological patients as identified by autopsy.

BACKGROUND: Despite progress in diagnostic procedures, clinical diagnosis is not always confirmed by an autopsy. An autopsy is a valuable tool in evaluating diagnostic accuracy. OBJECTIVES: The aim of the study was to compare clinical diagnoses of immediate causes of death with autopsy findings in patients with hematological malignancies or aplastic anemia. MATERIAL AND METHODS: In this study, the results of 154 autopsies (1993-2004) of patients with hematological diseases were reviewed and compared with clinical data. The most probable causes of death in the case of particular hematological diseases as well as the discordances between clinical and autopsy diagnoses and their relation to the clinical characteristic were identified in the studied cohort, which primarily included patients whose death at that particular time was not explained by the clinical course, and in 50% of cases was sudden. RESULTS: Although various combined infections have been found to be responsible for the largest number of deaths (26.6%), the most common single cause was myocardial infarction (29 patients, 18.8%). The discordance between clinical and post-mortem diagnoses of immediate causes of death was found in 55 patients (35.7%; 95% CI 28.2-42.8%), with 50.9% of cases considered class I discrepancies according to Goldman's criteria. The myocardial infarction was found to be clinically undiagnosed in 69% of cases. In 41% of cases, it was a class I discrepant diagnosis. CONCLUSIONS: This data suggests that hematological patients require special attention and probably preventive measures concerning coronary heart disease, particularly during the initiation of antineoplastic therapy.

[Current opinion in pathogenesis of pheochromocytoma]. / Wspólczesne poglady na patogeneze guza chromochlonnego.

Pheochromocytoma is a neuroendocrine tumor with significant clinical relevance. Is one of the causes of secondary hypertension. Most of the tumors are benign, but sometimes malignant cases are seen and there prognosis is unfavorable. So far, none of the factors which could initiate development of pheochromocytoma are known, besides genetic ones. In this review, most common familial syndromes connected with pheochromocytoma are characterized.

Morphofunctional Renal Alterations in Progeny of Mice Fed Rhodiola kirilowii Extracts or Epigallocatechin During Pregnancy and Lactation.

Treating infections in pregnant patients is potentially dangerous even when herbal medicines are used. Many herbal medicines, among them extracts from plants of Rhodiola genus, have antimicrobial, anti-inflammatory, and immunostimulatory properties owing to their polyphenol content; they may, however, affect fetal development due to their antiangiogenic properties. The aim of this study was to explain whether daily feeding pregnant and lactating mice with 20 mg/kg Rhodiola kirilowii aqueous (RKW) or 50% hydro-alcoholic (RKW-A) extracts, or 0.2 mg/kg epigallocatechin (EGC, antiangiogenic compound of Rhodiola extracts), may lead to abnormalities in morphology and function of the kidneys of adult progeny. Such abnormalities were not observed in the kidneys of 6-week-old offspring, neither in RKW nor in the control group. However, the progeny of RKW-A- or EGC-fed mothers presented morphometric abnormalities in the kidney structure, with a significantly higher number of glomeruli/mm2 and a lower diameter of glomeruli (RKW-A group) or a significantly higher glomeruli diameter (EGC), than in the control and RKW groups. Abnormalities in serum vascular endothelial growth factor, tumor necrosis factor (TNF)-alpha, urea, creatinine, and cystatin C levels were also found. We recommend caution in long-term use of RKW-A extract and EGC-rich foods during pregnancy and lactation.

The calcium-sensing receptor and vitamin D receptor expression in tertiary hyperparathyroidism.

The parathormone (PTH) production is controlled by calcium and vitamin D, which interact with the calcium-sensing receptor (CaSR) and vitamin D receptor (VDR), respectively. All of these elements control calcium homeostasis, which is crucial for many physiological processes. Thus, impairment of the upstream component of this system, e.g. a decrease of CaSR and/or VDR, could result in hyperparathyroidism (HPTH). Therefore, the aim of this study was to assess the expression of CaSR and VDR in a tertiary form of HPTH (T-HPTH). The study involved 19 T-HPTH patients qualified for parathyroidectomy and 21 control parathyroids harvested from multi-organ cadaver donors. The small fragments of harvested glands were homogenized and used for Western blot analysis, whereas the remaining tissues underwent routine hematoxylin-eosin staining or immunostaining for CaSR and VDR. Among 64 T-HPTH parathyroids, 58 revealed the morphology of benign hyperplasia, 2 were identified as adenoma and 4 were classified as normal; some glands displayed a mixed histological phenotype. Western blot analysis revealed a decrease of CaSR and VDR in hyperplasia and adenoma-derived samples. However, no correlation between the types of hyperplasia and receptor expression was observed. On the other hand, microscopic analysis of CaSR- and VDR-immunostained sections revealed a highly differentiated and significantly decreased mean expression of both receptors, which correlated with parathyroid histology. The reason behind the impaired expression of CaSR and VDR in T-HPTH is unclear. It presumably results from constant parathyroid stimulation at the stage of S-HPTH, followed by further development of polyclonal autonomy. However, the verification of this thesis requires further study.

Synchronous occurrence of gastrointestinal stromal tumors and other primary gastrointestinal neoplasms.

AIM: To review clinical and pathologic features of Gastrointestinal stromal tumors (GISTs) occurring synchronously with other primary gastrointestinal neoplasms. METHODS: Twenty-eight patients with primary GIST were treated at our institution between 1989 and 2005. Clinical and pathologic records were reviewed. RESULTS: The gastrointestinal stromal tumor occurred simultaneously with other primary GI malignancies in 14% of all patients with GIST. The synchronous stromal tumors were located in the stomach and were incidentally found during the operation. The coexistent neoplasms were colon adenocarcinoma, gastric cancer (2 cases) and gastric lymphoma. CONCLUSION: The synchronous occurrence of GISTs and other gastrointestinal malignancies is more common than it has been considered. The development of gastrointestinal stromal tumors and other neoplasms may involve the same carcinogenic agents.

Expression of the membrane complement regulatory proteins (CD55 and CD59) in human thymus.

CD59 is one of the key molecules involved in cell protection against autologus complement. The fact that complement regulatory proteins are able to prevent hyperacute rejection of organs in pig to primate model, raises the question of possible complement regulatory protein (CRP) involvement in the maturation of immunological system. We report here that in foetal and postnatal human thymus, CD59 and CD55 are primarily located on Hassall's corpuscles and medullary epithelial cells. This localization highly correlates with the expression of CD30L, which is the member of the tumour necrosis factor superfamily. Additionally, TUNEL technique was used to visualize distribution of apoptotic cells in the thymus, which revealed the presence of apoptotic cells closely associated with the Hassall's corpuscles. The observed co-localization of CD59, CD55 and CD30L might suggest an involvement of the complement system in thymic selection in humans.

Morphometric and functional abnormalities of kidneys in the progeny of mice fed chocolate during pregnancy and lactation.

Even most commonly consumed beverages like tea, coffee, chocolate and cocoa contain methylxanthines, biogenic amines and polyphenols, among them catechins, that exhibit significant biological activity and might profoundly affect the organism homeostasis. We have previously shown that 400 mg of bitter chocolate or 6 mg of theobromine added to the daily diet of pregnant and afterwards lactating mice affected embryonic angiogenesis and caused bone mineralization disturbances as well as limb shortening in 4-weeks old offspring. The aim of the present study was the morphometric and functional evaluation of kidneys in the 4-weeks old progeny mice fed according to the protocol mentioned above. Progeny from the mice fed chocolate presented considerable morphometric abnormalities in the kidney structure, with the lower number of glomeruli per mm2 and their increased diameter. Moreover, higher serum creatinine concentration was observed in that group of offspring. No morphometric or functional irregularities were found in the progeny of mice fed theobromine. Abnormalities demonstrated in the offspring of mice fed chocolate are not related to its theobromine content. Consequently, identification of active compound(s) responsible for the observed effects is of vital importance.

[Focal fatty change (FFC) imitating liver malignancy. Own cases and review of literature]. / Ogniskowe stluszczenie watroby (focal fatty change--FFC) pod postacia guzów imitujacych chorobe nowotworowa. Spostrzezenia wlasne i przeglad literatury.

UNLABELLED: Focal fatty change (FFC) may occur in the form of a single or numerous nodules of different size, located in the liver with otherwise normal structure. These changes, especially when they are large and single, pose an important diagnostic problem as their clinical and radiological picture may imitate malignancy. In the paper we report two cases of large hepatic tumors (12 cm and 8 cm) in patients, who had no factors predisposing to fatty liver changes (such as alcohol abuse, drugs, obesity, hormone disturbances, impaired blood flow through the liver or metabolic disturbances). In microscopic examinations the nodules were diagnosed as foci of large-droplet hepatocellular steatosis. Apart from these changes the liver was normal. CONCLUSION: FFC belongs to a group of pseudotumor changes. It occurs in rare cases and should be distinguished from diffuse changes observed frequently. In the differential diagnosis, the following must also be considered: primary hepatocellular tumors with fatty change, FNH with fatty change, mesenchymal tumors containing adipose tissue, fatty macro-regenerative nodule, adipocytic pseudotumor of the Glisson's capsule.

[Comparison of CD15, galectin-3 and HBME-1 expression in follicular thyroid neoplasms]. / Porówmanie ekspresji CD15, galektyny-3 i HBME-1 w nowotworach pecherzykowych tarczycy.

INTRODUCTION: Estimation of malignancy in thyroid follicular neoplasms is a common diagnostic problem, thus revealing of differences in expression of some antigens in both benign and malignant lesions seems to be essential. The aim of this study is to evaluate the immunohistochemical expression of CD15, galectin-3 and HBME-1 in follicular adenomas and carcinomas. MATERIAL AND METHODS: Samples of 38 follicular adenomas (23 "classical", 5 with intracapsular invasion, 10 oncocytic) and 15 follicular carcinomas (9 "classic", 6 oncocytic) were stained immunohistochemically with anti-CD15, galectin-3 and HBME-1. RESULTS: In the whole group we found statistically significant differences in CD15 expression between follicular adenomas and carcinomas. "Classic" follicular carcinomas (without oncocytic tumors) showed stronger CD15 and HBME- 1 expression than "classic" adenomas. Adenomas with intracapsular invasion differed from "classic" adenomas only in HBME-1 expression. In oncocytic tumors the expression of examined antigens was similar. CONCLUSIONS: 1. In the group of nonoxyphilic tumors positive reaction with HBME-1 was more common in adenomas with intracapsular invasion and carcinomas, but positive reaction with anti-CD15--only in carcinomas. We suggest that reactivity with these antibodies could mark malignancy. 2. Oncocytic tumors had similar expression of CD15 and HBME-1 and galectin-3.

P-glycoprotein expression influences the result of 99mTc-MIBI scintigraphy in tertiary hyperparathyroidism.

Precise localization of parathyroid glands using 99mTc-labeled hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy could be affected by various biological factors. There is increasing evidence that radiotracer retention could be controlled by members of multidrug resistance (MDR) system, especially P-glycoprotein (P-gp). Since the role of P-gp in tertiary hyperparathyroidism (T-HPTH) scintigraphic studies is poorly recognized, the aim of the study was to compare the correlation between parathyroid P-gp expression and results of their scintigraphy in T-HPTH versus primary hyperparathyroidism (P-HPTH). P-HPTH (n = 19) and T-HPTH (n = 18) patients were subjected to 99mTc-MIBI scintigraphy followed by surgical treatment. The parathyroid glands were assessed in routine hematoxylin-eosin staining and P-gp expression was analyzed using immunohistochemistry. Parathyroids collected during cadaver donor multi-organ harvesting were used as a control. It has been found that P-HPTH-derived parathyroid glands with predominating adenoma morphology expressed less P-gp, as compared to P-gp-rich T-HPTH glands, mainly displaying nodular or diffused hyperplasia phenotype. This finding reversely correlated with results of 99mTc-MIBI scintigraphy. However, we did not observe any difference in P-gp expression nor scintigraphy result between nodular or diffused hyperplasia. Altogether, these data suggest that P-gp overexpression in T-HPTH could be responsible for decreased sensitivity of 99mTc-MIBI scintigraphy in those patients. Therefore, the recently proposed reduced neck exploration or limited parathyroid resection on the basis of scintigraphy could create the risk of persisted/recurrent hyperparathyroidism. However, this problem requires further study.

Carcinoma, a fibrolamellar variant--immunohistochemical analysis of 4 cases.

BACKGROUND/AIMS: To analyze, by means of immunocytochemistry, the cases of fibrolamellar variant of hepatocellular carcinoma (FLC), diagnosed in our Department. METHODOLOGY: The material comprised 4 FLC cases of tumors resected surgically. Besides the routine morphological assessment, we used a panel of immunohistochemical stainings including: hepatocellular cytokeratin, CK7, CK19, Ki67, PCNA, chromogranin A, synaptophysin, NSE, insulin, calcitonin, parathormon, CD34, EBV (LMP), Bcl2, cyclin D1. RESULTS: In 3 out of 4 cases, we observed co-expression of CK7 with hepatocellular CK. In addition, there was positive staining with some endocrine markers in the majority of patients. In one case, we found strong cyclin D1 immunoreactivity which correlated with EBV (LMP) immunoreactivity, in the same patient. The score of PCNA positivity varied between 15 and 90%. In all cases Ki67 was negative. CONCLUSIONS: The incidence of FLC, among all hepatocellular carcinomas diagnosed in our Department was 5.1%. In accordance with other reports, all our FLC cases were young patients without underlying liver disease. We were unable to find a correlation between FLC cellular immunophenotype, and histological and clinical markers of malignancy. In addition, it appears that PCNA is a better marker of cell-proliferation in FLC than Ki67. The significance of EBV infection in FLC requires further study.

[Rare causes of interstitial nephritis in two children]. / Rzadkie przyczyny sródmiazszowego zapalenia nerek u dzieci--prezentacja dwóch przypadków.

UNLABELLED: Interstitial nephritis (IN) can occur as a result of different injury factors, among them: infections, drugs, toxins. The aim of the study was the presentation of rare causes of IN in 2 patients who were hospitalized in the Department of Pediatrics and Nephrology of Medical University of Warsaw. Case 1. A 15-years-old girl, with biopsy proven IN, who presented with a slight impairment of kidney function (creatinine level 1.1 mg/dl) and symptoms of tubulopathy at the beginning of the illness. Hypergammaglobulinemia, anemia, increase of CRP level and high ESR were noticed. Among others causes CMV infection was suspected. After CMV detection seroconversion in titres of anti- CMV IgM and IgG antibodies was observed. Kidney biopsy revealed IN and positive reaction to CMV antigen in tubular epithelial cells. Case 2. A 12,5-years-old boy with acute renal failure (ARF) (creatinine and urea concentration respectively: 11.3 mg/dl, 131.4 mg/dl) was admitted to the hospital. In kidney biopsy acute IN with tubulopathy and intense involvement of renal tissue was found. In further investigation inhaled stimulating factor was suspected as the possible cause of renal changes development - IN and ARF. CONCLUSION: Considering the etiology of IN in children, CMV infection, the application of drugs and other chemical substances should be mentioned among the rare causes of the illness.

WITHDRAWN: Study coexistence albumin, fibrinogen and complement on surface blood vessels and placental.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Antigenic profile of muscularis mucosae and muscularis propria of the urinary bladder.

BACKGROUND: Differentiation between the muscularis mucosae (MM) and muscularis propria (MP) of the bladder remains challenging. OBJECTIVE: To identify MM- and MP-specific antigens that could be of potential value for staging of urothelial carcinoma in a pilot study. METHOD: The expression of 12 protein antigens in 11 human bladder specimens was examined. There were 5 post radical cystectomy specimens and 6 normal bladder autopsy specimens. Antibodies against actin, caldesmon, type IV collagen, cytokeratin, desmin, elastin, fibronectin, filamin, laminin, miotilin, smoothelin, and vimentin were used. Slides were stained with immunohistochemical reagents and assessed using light microscopy. The intensity of the immune reaction within MM and MP was evaluated in a four-level scale as negative and weakly, moderately or strongly positive. RESULTS: The presence of MM was noticed in 63.6% of specimens. The expression of desmin, filamin, and smoothelin was stronger within MP compared to MM in all cases. Stronger reaction with anti-type IV collagen antibodies was noticed within MP in 80% of the cases. In the whole study group, the expression of vimentin was stronger within MM than MP. CONCLUSIONS: MM and MP cells are of different antigenic characteristics. This can be used in the microscopic diagnostics of selected cases. The results need to be validated in a series of specimens from transurethral resection.