Multiple Sclerosis (MS) is a chronic disease, but in rare fulminant cases rapid progression may lead to death shortly after diagnosis. Currently there is no diagnostic test to predict disease course. The aim of this study was to identify potential biomarkers/proteins related to rapid progression. We present the case history of a 15-year-old male MS patient. Cerebrospinal fluid (CSF) was taken at diagnosis and at the time of rapid progression leading to the patient’s death. Using isobaric tag labeling and nanoflow liquid chromatography in conjunction with matrix assisted laser desorption/ionization time of flight tandem mass spectrometry we quantitatively analyzed the protein content of two CSF samples from the patient with fulminant MS as well as one relapsing-remitting (RR) MS patient and one control headache patient, whose CSF analysis was normal. Seventy-eight proteins were identified and seven proteins were found to be more abundant in both fulminant MS samples but not in the RR MS sample compared to the control. These proteins are involved in the immune response, blood coagulation, cell proliferation and cell adhesion. In conclusion, in this pilot study we were able to show differences in the CSF proteome of a rapidly progressing MS patient compared to a more typical clinical form of MS and a control subject.

Objectives: Individualized chemotherapy for breast cancer improves the outcome. Anthracyclines target the enzyme topoisomerase IIα (TOP2A). We set out to perform a retrospective study of the presence of gene abnormalities and the expression of TOP2A in a cohort of breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy. Methods: Forty-three patients with 45 breast cancers were treated with neoadjuvant docetaxel-epirubicin with/without capecitabine chemotherapy. The TOP2A status of the cancers, determined retrospectively by fluorescent in situ hybridization and immunohistochemistry, was analyzed in relation to the standard clinical and pathological data. Results: Clinically and pathologically complete remission (pCR) was achieved in 15 (33.3%) and 9 (20%) cases, respectively. The TOP2A gene was amplified in 2 human epidermal growth factor receptor 2 (HER2)-positive cancers (8%), and 32 (84.2%) overall exhibited TOP2A expression in >15% of the cells. The expression of TOP2A exhibited a strong correlation with the expression of Ki67 (R = 0.743, p < 0.001), and was negatively correlated with estrogen receptors (ER; R = 0.404, p = 0.012) and progesterone receptors (R = 0.430, p = 0.007). The expression of TOP2A was not related to the amplification of the TOP2A gene or the HER2 status of the tumor. The proportions of Ki67- and TOP2A-positive tumor cells were significantly reduced after chemotherapy (56.1 ± 23.6 vs. 19.0 ± 27.7%, p = 0.004, and 41.0 ± 27.9 vs. 12.7 ± 24.8%, p < 0.001, respectively). The development of pCR was related to a high grade (p = 0.054), ER negativity (p = 0.027) and high TOP2A expression (p = 0.037). The expression of TOP2A was an independent predictor of pCR (OR = 1.460, for every 10% increase, 95% CI: 1.016–2.096, p = 0.041). After a median follow-up time of 31.0 months, neither relapse-free survival nor overall survival was related to the tumor response. Conclusions: TOP2A expression is a marker of the tumor’s proliferation rate and sensitivity to anthracycline-based chemotherapy, and does not depend on the amplification of its gene.

BackgroundThe usage of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for the diagnosis of solid pancreatic cancer is increasing, however mainly retrospective studies are available about the detailed methods of sampling.MethodsTo compare prospectively the diagnostic yield of EUS-FNA samples obtained with slow-pull (SP) and with standard suction technique (SS).ResultsEUS-FNA sampling was diagnostic in 72 of 92 cases (78.3%). Diagnostic yield was 67.4% in the SS and 65.2% in the SP group. The number of smear pairs (1.84 vs. 3.56; p < 0.001) and blood contamination (1.50 vs. 2.19; p < 0.001) were significantly higher in the SS group, which resulted in lower rate of diagnostic samples (41.8% vs. 30.0%; p = 0.003). There was no difference in the cellularity (1.58 vs. 1.37; p = 0.2554), or in the sensitivity and specificity in the identification of malignancy between SP and SS subgroups (69.9, 100% vs. 73.5, 100%). Histological samples were obtained in 60 cases (with SP: 49 cases; with SS: 46 cases). There was no difference in the diagnostic yield of histological samples between the groups (63 and 58.7%).ConclusionThe diagnostic yield, the cellularity of smears and the rate of acquiring sufficient histological material are similar in the SP and SS group, but due to lower bloodiness and decreased number of slides, the pathological diagnosis is faster and more cost-effective.

Introduction: Intraoperative touch imprint cytology (TIC) of the sentinel lymph node(s) (SLN(s)) in the treatment of breast cancer has significantly reduced the number of axillary block dissections (ABD) required during second surgeries. Based on recent studies, ABD was not considered necessary if the presence of tumor cells/micrometastasis was confirmed in the SLN(s) or in the case of macrometastases in a patient group meeting the inclusion criteria for the ACOSOG Z0011 study. Our aim was to determine the sensitivity and usefulness of TIC with regard to these results. Methods: TICs of the SLN(s) were examined in 1168 patients operated on for breast cancer. The method was also analyzed retrospectively based on the guidelines for the Z0011 study. During TIC, new samples were cut every 250 mm; impression smears were evaluated after being stained with hematoxylin eosin. Results: TIC confirmed metastasis in 202 cases (202/1168, 17.29%). Metastasis was confirmed in SLN(s) in 149 additional cases during a final histological examination. The sensitivity of TIC was found to be 57.18%, and its specificity was 99.63%. An analysis was then performed except for cases that met the inclusion criteria for the Z0011 study and with metastasis smaller than 2 mm (micrometastasis/isolated tumor cells) considered to be positive during intraoperative cytology. The sensitivity of the method decreased to 34.23%, while its specificity was still high at 99.76%. Conclusions: Based on the new guidelines for ABD, imprint cytology cannot be considered a beneficial and cost-effective intervention in the surgical treatment of early breast cancer.

Breast cancer at a relatively young age with a poor prognosis is currently exhibiting an increasing incidence. In a retrospective cohort analysis of early breast cancer cases after surgery from our institutional patient registry, 141 patients aged ≤ 40 years constituted the younger group, with 300 randomly selected patients aged >40 years as controls. A significant and steady increase was found in the relative number of younger cases during the years 2004-2009. The histological type and grade and the lymph node status of the cancers differed significantly between the two groups, with more aggressive biological behaviour, a more advanced stage and a worse prognosis in the younger group. Half of the cancers in the younger cohort were ER-negative, while two-thirds in the control group were ER-positive. Comparatively more tumours were PR-positive and HER2-negative in the control group than in the younger group. The rates of triple-negative cases were 25% and 13% in the younger age and the control group, respectively (p = 0.026). Significantly higher mastectomy and axillary block dissection rates were observed in the younger age group, and more chemotherapy was administered than in the control group. Our findings demonstrate the significance of breast cancer in cases aged <40 years, and draw attention to the need for appropriate care in these cases.