[Importance of expression of DNA repair proteins in non-small-cell lung cancer]. / Význam stanovovania expresie DNA reparacných mechanizmov u nemalobunkového karcinómu plúc.

BACKGROUND: Proteins XRCC1 and ERCC1 are involved in DNA repair. XRCC1 plays a role in DNA base excision repair and ERCC1 in nucleotide excision repair pathway. Higher expression profile of both proteins in cancer cells may contribute to development of drug resistance. ERCC1 is involved in removal of platinum adducts and might be a potential predictive and prognostic marker in NSCLC (non-small-cell lung cancer) treated with a cisplatin-based regimen. The purpose of study was determination of XRCC1 and ERCC1 levels and their correlation with basic clini-copathological parameters in NSCLC. PATIENTS AND METHODS: In this study, 107 tumor samples diagnosed as NSCLC were immunohistochemically examined for expression of XRCC1 and ERCC1 proteins. Our results were compared to basic clinicopathological parameters: type of tumor, tumor grade and stage of disease. For statistical analysis, the chi-square test was used. RESULTS: In squamous cell carcinoma and large cell carcinoma samples, the XRCC1 protein level was twofold higher (60% of positive samples) than in adenocarcinoma samples (35.5% of positive samples). We have found statistical correlation between XRCC1 protein expression and type of tumor (p = 0.0306). On the other hand, the statistical importance between the protein level versus grade and stage was not found. In the case of the ERCC1 protein, we observed the highest protein level in adenocarcinoma (64.5%) and squamous cell carcinoma (62.5%) samples. Next, we determined a significant difference in content of XRCC1 versus ERCC1 (35.5% vs 64.5%) in adenocarcinoma samples. Statistical chi-square test did not reveal any correlation between ERCC1 status and clinicopathological parameters. CONCLUSION: According to our results, XRCC1 represents an important mechanism of DNA repair in squamous cell and large cell carcinomas. Besides that, expression of XRCC1 was in correlation with type of tumor. In patients with adenocarcinoma and squamous cell carcinoma, we could assume increased resistance to platinum-based therapy because of high expectation of ERCC1 protein expression. However, its levels did not correlate with monitored clinicopathological parameters. The ERCC1 protein will be possibly an independent prognostic factor in NSCLC. To prove a true survival benefit of patients with expression of ERCC1, prospective validation of ERCC1 before clinical implication is needed in the future.

[Targeted therapy of melanoma: fact or fiction?]. / Cielená liecba melanómu: fakt alebo fikcia?

Advanced malignant melanoma is incurable by the current means of therapy. Traditional morphological classification (nodular melanoma, lentigo maligna melanoma, nevoid melanoma etc.) does not have any significant prognostic or predictive impact. Recent advances in molecular pathogenesis and the availability of targeted therapies have produced several positive results. In the near future, the main challenge for pathologists, geneticists and oncologists will be the identification of accurate therapeutic targets, as well as mechanisms of resistance, in melanoma in the particular patient in care.

Celiac disease manifested during the treatment of chronic hepatitis C by pegylated alpha interferon and ribavirin.

Authors report a case of patient suffering from haemophilia A and hepatitis C virus infection acquired probably after blood transfusions and substitution factors application. He was treated with pegylated interferon alpha and ribavirin, with the development of malabsorption symptoms during the therapy. Celiac disease was established by histological, histochemical and serological examinations. oth, interferon alpha and ribavirin treatment as well as virus of hepatitis C may trigger coeliac disease in genetically predisposed individuals. The immunological mechanism of celiac disease include balance disruption between Th1 and Th2 immunological response with Th1 predominance. Only few similar cases have been published in the professional literature to date. Development of celiac disease during interferon alpha therapy with haemophilia A was not published until now (Fig. 3, Ref. 13).

Immunohistochemical evaluation of Pi class glutathione S-transferase expression in invasive breast carcinoma.

OBJECTIVES: The aim of our work was to determine the expression of Pi class glutathione S-transferase (GSTP1) in 43 samples of invasive breast carcinoma and compare results versus normal breast cells. BACKGROUND: Breast cancer is the commonest cancer in women. Despite advances in early detection and more efficacious adjuvant chemotherapy, a part of patients with early-stage have reccurent disease. In these cases the development of resistance to therapy is observed. The glutathione S-transferases (GSTs) are potentially involved in tumour chemoresistance. METHODS: Enzyme immunohistochemical method was chosen for the detection of GSTP1 and its expression was compared in breast cancer cells versus normal breast cells. RESULTS: We have found that majority (63%) of breast carcinomas shows GSTP1 positivity (nuclear and cytoplasmic immunoreactivity). It is expected that GSTP1 positive tumours would show a poorer prognosis than GSTP1 negative ones. CONCLUSION: Immunohistochemistry is a useful method for investigating the expression and cellular localization of GSTP1 within tumours. It may be applied to a routine clinical test and it can serve as a marker for resistance to chemotherapy (Tab. 1, Fig. 4, Ref. 20). Full Text in free PDF www.bmj.sk.

Expression of MDR proteins in breast cancer and its correlation with some clinical and pathological parameters.

The aim of this work was to determine the expression of the multidrug resistance (MDR) proteins, namely MDR1 (P-glycoprotein), MRP1 (multidrug resistance-related protein) and LRP (lung resistance-related protein), in 87 samples of breast carcinoma. Detection of these proteins was provided by using indirect enzymatic immunohistochemistry. Our findings were compared with the other clinical and pathological parameters: expression of Her2/neu, estrogen receptor status (ER), progesteron receptor status (PR), histological grade and regional lymph node status. For statistical analysis, non-parametric two sided Mann-Whitney-U test was used. Majority of breast carcinoma specimens show positivity for these proteins. The MDR1 and MRP1 signal was found in the cytoplasm of cancer cells. The expression of LRP was detected in the cytoplasm close to the nuclear membrane. The samples were positive for MDR1 protein in 57%, for MRP1 in 84% and for LRP in 79%. Comparing our results with other clinical and pathological parameters, negative correlation between ER, PR and MDR1 expressions and histological grading status was found. No associations were observed between the MRP1 and LRP proteins and histological grading, as well as between the expression of three MDR proteins and the other clinically relevant parameters. In conclusion, high frequency of expression of MDR proteins in breast carcinoma cells suggests, that these proteins might be an important factor of drug resistance in breast carcinoma. Nevertheless, the negative correlation between the histological grade of malignancy of tumor and the expression of ER, PR and MDR1 indicates possible influence of progressive tumor cell de-differentiation. However, this finding has to be confirmed in additional evaluations.

Immunohistochemical study of melanocytic differentiation antigens in cutaneous malignant melanoma. A comparison of six commercial antibodies and one non-commercial antibody in nodular melanoma, superficially spreading melanoma and lentigo maligna melanoma.

In certain primary and metastatic malignant melanomas diagnostic problems may arise due to their cytologic features and/or absence of synthesis of melanin. As the "classic" combination of S-100 protein and HMB-45 may occasionally fail to stain cells of malignant melanoma, we have tested a series of commercially accessible antibodies which were so far not compared by other authors in the three most frequent subtypes of this tumor. In surgical specimens from 104 cutaneous malignant melanomas (40 nodular melanomas, 46 superficially spreading malignant melanomas and 18 lentigo maligna melanomas) the staining intensity and the proportion of neoplastic cells stained with antibodies to S-100 protein, HMB-45, NKI/C3, NKI/beteb, MART 1 (Melan A), KBA 62 and Mitf was semiquantitatively analysed. The use of this group of antibodies against melanoma-associated antigens revealed it to be a favourable supplement for the bioptical or cytological diagnosis of malignant melanoma in case the traditional/conventional combination of S-100 protein and HMB-45 antibody fails. According to the authors' experience the antibody against KBA 62 has shown to be the most effective antibody followed by the antibodies against MART-1 (Melan A) and NKI/C3.

[Pulmonary thromboembolism over a 25-year period in data from the Institute of Pathology of the P.J. Safarik Medical School in Kosice]. / Výskyt plúcnej trombembólie v materiáloch Ustavu patológie Lekárskej fakulty Univerzity P. J. Safárika v Kosiciach v odstupe stvrt'storocí.

Based on a review of archival autopsy protocols an analysis of the frequency of pulmonary thrombembolism in consecutive autopsy material is presented. The study interval for the analysis was oriented to the period between the years 1949-2000. Our analysis has shown a gradual progression of incidence of pulmonary thrombembolism, as demonstrated in relative figures. The applied preventive measures against the development of thrombosis during hospitalization have not substantially contributed to decreasing its frequency, what is not in accord with some recent observations from other countries.

Calcium oxalate granuloma of the nose of a chronically dialysed nephritic patient.

The patient was a 54-year-old woman who had been suffering from chronic tubulo-interstitial nephritis for about seven years, requiring haemodialysis. More recently, she developed a polypoid mass in the left nasal cavity causing discomfort on breathing and slight epistaxis. The tumour was of gritty consistency and measured 28 x 8 x 5 mm. Microscopy showed a lobulated almost cystic structure composed of granulation tissue with comparatively few plasma cells and many multinucleated giant cells lining the spaces filled with crystalline deposits of calcium oxalate.

[Immunohistochemical analysis of renal angiomyolipoma]. / Imunohistochemická analýza angiomyolipómu oblicky.

Immunohistochemical analysis of 6 cases of renal angiomyolipoma not related to tuberous sclerosis proved the same rate of expression of HMB 45 and NKI/C3 as well in epithelioid smooth muscle cells of the tumours. Beyond this, an unspecific expression of alpha 1-antitrypsin and alpha 1-antichymotrypsin was found which has not been mentioned in the literature up to now.

Actinomycosis of the middle ear.

Another case of actinomycosis of the ear is described in a nine-year-old boy, drawing attention to the increasing incidence of diseases of the ear considered to be rare. The patient presented with the clinical signs of chronic purulent otitis media, not responding to conservative treatment. After the diagnosis of actinomycosis was established the patient was treated by surgery and long-term antibiotic medication, responding favourably.

Gastroprotective effect of malotilate in indomethacin- and ethanol-induced gastric mucosal damage.

Malotilate as a synthetic substance shares comparable hepatoprotective properties with various flavonoids. The gastroprotective effect of some flavonoids prompted us to ascertain the similar effectiveness of malotilate. The possible gastroprotectivity was examined in gastric mucosal damage in rats induced by indomethacin (20 mg.kg-1) or ethanol (96%). Oral pretreatment with malotilate (25, 50, 100, 200 and 400 mg.kg-1) reduced the extent of lesions induced by both indomethacin and ethanol. Histological analyses also revealed a mitigating effect on the severity of gastric mucosal lesions. Similar results were obtained in the group of rats pretreated with 5 mg.kg-1 indomethacin followed by oral administration of 96% ethanol. This finding suggests that the effect of malotilate on rat gastric mucosa is independent of endogenous prostaglandin production.