Expression of ezrin and moesin in primary breast carcinoma and matched lymph node metastases.

Ezrin, radixin, moesin (ERM) are important membrane-cytoskeletal crosslinkers and are suggested to play important role in cancer progression and metastasis. Even though ERM proteins were generally considered to be functionally redundant and the most studied was ezrin, recent studies highlight their distinct roles in metastatic process. Little information is available regarding the role of individual ERM proteins and their phosphorylated forms in human breast cancer. Our study is the first to examine expression of ezrin, moesin and their phosphorylated forms in primary breast tumors and matched lymph node metastases (LNMs) and their correlation with clinicopathological variables. A total of 88 primary breast cancer, 91 LNMs, 54 intraductal carcinoma and 26 normal adjacent breast tissue samples from tissue microarrays were studied. Expression was determined by immunohistochemistry, the intensity and number of positive cells was scored. Statistical analysis of protein expression and patients' age, tumor grade and hormonal status was performed. No statistical significant difference was found in ezrin, moesin, p-ezrinTyr353 and pan-p-ezrinThr567/radixinThr564/moesinThr558 expression between primary tumors and LNMs. Even though it was not significant, moesin expression varied between primary tumors, intraductal carcinoma, normal breast adjacent tissue and LNMs. A significant positive correlation between moesin and tumor grade has been proven. Even though primary tumors and matched LNMs did not show different expression patterns, moesin correlated significantly with higher tumor grade. Its positivity in intraductal carcinoma and normal breast tissue adjacent to cancer might indicate its role in tumor intiation/progression.

Prediction of additional lymph node involvement in breast cancer patients with positive sentinel lymph nodes.

Axillary lymph node dissection (ALND) has traditionally been the principal method for evaluating axillary lymph node status in breast cancer patients. In the past decades sentinel lymph nodes biopsy after lymphatic mapping has been used to stage the disease. The majority of sentinel lymph nodes (SLN) positive patients do not have additional metastases in non-sentinel nodes (non-SLN) after additional ALND. These patients are exposed to the morbidity of ALND without any benefit from additional axillary clearence. In the present study we would like to asses the criteria for selecting those patients, who have high risk for non-SLN metastases in the axilla in cases of positive SLN. In this retrospective analysis, clinical and pathologic data from 163 patients who underwent SLN biopsy followed by ALND were collected. Following clinical and pathological characteristics were analyzed to predict the likehood of non-SLN metastases: age, staging, histologic type and grading of the tumors, hormonal receptor status, HER-2 receptor status and Ki-67 protein, angioinvasion, metastases in SLN and non-SLN. Relative frequencies of individual characteristics between sample groups were statistically tested by Chi-square test at significance level p=0.5, when sample sizes in groups were small (≤5) by Fisher´s exact test. Metastasis in SLN were present in 67 (41%) of patients, 48 patients (29,4%) had metastasis also in non-SLN. The ratio between non-SLN positive / non-SLN negative lymph nodes in patients with positive SLN increases with the stage of the disease, the difference between values for the pT1c and pT2 stadium was statistically significant (p = 0.0296). The same applies to grading, but the differences were not significant (p>0.05). We could not find significant differences for angioinvasion of the tumor, probably for small number of patients with angioinvasion (p>0.05).Only the stage of the tumor was shown to be significant in predicting the metastasis in non-SLN in our group of breast cancer patients with positive SLN Nearly 80% of the patients of 70 years and older displayed no benefit from axillary staging, because of negative SLN as well as non-SLN, although thanks to the small sample size this was not a statistically significant result. Furthermore, current recommendations for axillary staging in breast cancer patients are discussed.

COX-2, p16 and Ki67 expression in DCIS, microinvasive and early invasive breast carcinoma with extensive intraductal component.

BACKGROUND: Recent studies have showed a significant association between the combination of COX-2, p16 and Ki67 overexpression and incidence of subsequent invasive carcinoma in a subgroup of treated ductal carcinoma in situ (DCIS) and the indicated prognostic value of COX-2, p16 and Ki67 in early breast cancer. Based on the continual model of carcinogenesis and the mentioned results, we hypothesize, that if COX-2, p16 and Ki67 expression is prognostic for DCIS future behaviour, the expression level of the markers correlates also with different stages of breast carcinomas such as DCIS, microinvasive cancer and early invasive cancer with an extensive intraductal compound. The aim of this study was to compare the expression of COX-2, p16 and Ki67 in different stages of breast carcinoma such as pure DCIS, microinvasive cancer (T1mic) and invasive ductal carcinoma with an extensive intraductal component (IDC with EIC). The expression was assessed only in in situ component of the three subgroups (DCIS, T1mic, EIC) in order to show a possible correlation of COX-2, p16 and Ki67 with different stages of carcinogenesis. METHODS: We carried out a retrospective study using immunohistochemical staining to evaluate the expression of the markers COX-2, p16 and Ki67 in in situ lesions within three subgroups of tumors with the rising extant of invasive compound: in pure DCIS, microinvasive carcinoma (T1mic) and invasive carcinoma with extensive in situ component (IDC with EIC). Additionally, we performed a correlation analysis between the tumor subgroups and patients history data (age, parity, age of menarche, family and personal cancer history, breast feeding lengths, contraception intake, chest irradiation) as well as some of the tumor characteristics (tumor grade, multicentricity, necrosis). RESULTS: Distribution of p16 expression differed significantly among the three diagnoses. P16 score 1 was highest in the DCIS group whereas the lowest proportion was in IDC and p16 overexpression (score 2, 3) maintained this tendency (overexpression proportion in DCIS < T1mic < IDC), though this was not significant. The frequency of COX-2 and p16 overexpression (phenotype COX-2+p16+) was higher in EIC within invasive carcinoma in comparison to DCIS and T1mic and was rising gradually with the severity of the diagnosis (proportion in DCIS < T1mic < IDC). CONCLUSION: This is the first published study ever assessing the expression of COX-2, p16 and Ki67 markers in different breast tumors containing DCIS compound. Our results showed an increasing expression pattern of COX-2 and p16 with the rising severity of the diagnosis (expression was measured exclusively in in situ lesions within tumors containing different extant of invasiveness). The same relationship was showed for p16 marker alone. These data support different expression pattern of COX-2 and p16 markers in combination and p16 marker alone in "in situ lesions" according to the stage of carcinogenesis. This fact might be useful in the evaluation of further behaviour of early breast tumors (Tab. 3, Fig. 8, Ref. 29).

[Antibiotic resistance in nontyphoidal salmonellae serovars in the Czech Republic]. / Antibiotická rezistence u netyfových sérovaru Salmonella spp. v Ceské republice.

STUDY AIM: To determine antibiotic resistance and incidence of multidrug resistance among Nontyphoidal salmonellae serovars isolated from humans. MATERIAL AND METHODS: Consecutive Salmonella isolates from patients, recovered in 48 microbiology laboratories in May 2012, were analyzed in the respective reference laboratories at the National Institute of Public Health. Strains were re-identified and differentiated into serovars. Their minimum inhibitory concentrations (MICs) to 11 antibiotics were determined by the microdilution method. RESULTS: Of 25 serovars identified among 637 strains of Salmonella enterica, the most frequent were Enteritidis (87.0 %), Typhimurium (4.9 %), and monophasic Typhimurium 4,[5],12:i:- (2.0 %) and Mbandaka (0.6 %); other serovars were rare. Altogether 558 strains (87.6 %) were susceptible to all antibiotics tested and the remaining 79 strains were resistant to one or more antibiotics. The prevalence rates of resistance to individual antibiotics among 637 study strains were as follows: ampicillin 8.5%, tetracycline 5.7%, sulfamethoxazole 5.2%, cipro-floxacin 3.8%, and chloramphenicol 2.5%. Resistance to gentamicin, trimethoprim, and third and fourth generation cephalosporins was rare ( 0.5%) and none of the study strains showed resistance to meropenem. Three producers of extended spectrum beta-lactamase were multidrug resistant and two of them recovered from twins exhibited a different pattern of resistance. Resistant strains were most often assigned to the following serovars: Enteritidis (49.4%), Typhimurium (26.6%), and monophasic Typhimurium (15.2%). While only 7% (39 of 554 strains) of Enteritidis strains were resistant, the serovars Typhimurium and its monophasic variant 4,[5],12:i:- showed high rates of resistance, i.e. 66.7 and 92.3%, respectively. Furthermore, resistance was revealed in all strains of the serovars Virchow (n = 3), Kentucky (n = 1), and Newport (n = 1), in two of three strains of the serovar Infantis, and in one of two strains of the serovar Stanley. All five blood isolates were assigned to the serovar Enteritidis and one of them showed resistance to ciprofloxacin. Of 79 resistant strains, 26.6% showed resistance to ampicillin only and 24.1% to ciprofloxacin only, with multidrug resistance, i.e. resistance to three or more antibiotics, confirmed in 43.0% of strains. CONCLUSION: Despite a relatively low prevalence of resistance to the antibiotics tested among 637 study strains, the following alarming findings were made: Detection of Salmonella enterica strains resistant to ciprofloxacin as the drug of choice or to higher generation cephalosporins and multidrug resistance revealed in two thirds of the strains of the serovar Typhimurium and in all but one strains of its monophasic variant 4,[5],12:i:-.

Local recurrence rate in patients with DCIS.

UNLABELLED: The aim of this observational retrospective study was to evaluate the local recurrence rate of ductal carcinoma in situ of the breast (DCIS) and/or invasive breast cancer in patients with DCIS or microinvasive carcinoma of the breast after breast conserving or radical surgery. Secondary aim of the study was comprehensive assessment of the whole management of DCIS and its comparison with European guidelines. METHODS: The study was performed in a group of 41 women with DCIS or microinvasive cancer, who underwent surgical treatment (breast conserving or radical modified mastectomy) at the IInd Department of Gynaecology and Obstetrics, University Hospital Bratislava (UNB), during the period 2001-2009. Documentation and pathological examination data from paraffin embedded tissue sections were used as data source. We sent out questionnaires regarding data about additional postoperative treatment and course of the disease up to year 2010 with focus on recurrence or tumour de novo incidence. RESULTS: Breast conserving surgery was performed in 28 cases - 68 %, modified radical mastectomy in 13 cases. All cases of mastectomy were due to multicentricity and/or extensive tumour >4 cm. Additional surgery due to unsatisfactory marginal status was performed in 8 patients (3.28 %). Additional treatment such as radiotherapy and/or hormonal therapy received 19 patients. Van Nuyss Prognostic Index was reported in 17 patients on the basis of histopathological data. 27 patients completed and returned questionnaire. No DCIS recurrence nor infiltrating cancer or tumour de novo was reported in this group. CONCLUSION: We consider surgical management as adequate. Further material analysis is needed (Tab. 5, Fig. 1, Ref. 28).

Klion in the prevention of early complications following appendectomy.

The authors observations with prophylactic administration of metronidazole manufactured by the Gedeon Richter Company, Hungary (trade mark Klion) in children with phlegmonous appendicitis are reported. The drug was administered in three doses to 51 children. Results of bacteriology could be assessed in 42 children. The results of prophylactic administration of Klion in phlegmonous appendicitis were excellent. In our group there were no inflammatory wounds and/or intraperitoneal complications. For comparison, in a cohort of 1.008 children with phlegmonous appendicitis, without prophylaxis the rate of inflammatory complications was 3.62%. Klion has minimal side effects and is well tolerated and seems to be a superb drug for prophylaxis.

[Prophylactic administration of Klion in acute appendicitis]. / Profylaktické podání Klionu u akutní apendicitidy.

The authors present their experience with the prophylactic administration of metronidazole of Richter Co. Hungary (trade name Klion) in children with phlegmonous appendicitis. The preparation was administered in three doses to 51 children. The bacteriological results were evaluated in 42 children. The results of Klion administration in phlegmonous appendicitis were excellent. In the investigated group there were no wound inflammatory nor intraabdominal complications. For comparison the authors mention a group of 1008 children with phlegmonous appendicitis without prophylactic provisions where the number of inflammatory wound complications was 3.62%. Klion has minimal side-effects, was well tolerated and proved excellent for prophylactic administration.

[Determination of lactoferrin in the diagnosis of diseases of the pancreas]. / Stanovení laktoferinu v diagnostice onemocnení slinivky brisní.

In 29 patients with chronic pancreatitis, 15 patients with malignant tumours of the pancreas and in 30 controls lactoferrin in fluid aspirated from the duodenum was assessed during the cholecystokinin-secretin (CCK-S) test. As compared with the control group, its concentration is significantly higher in patients with chronic pancreatitis, but not in patients with malignant tumours of the pancreas. It is probable that estimation of lactoferrin in the CCK-S test may prove helpful in the differential diagnosis of pancreatic disease.