Cellular cohesiveness in benign and malignant thyroid follicular tumours varies significantly, but the difference is not useful in diagnosis of individual cases.

INTRODUCTION: The aim of our study was to search for new, readily available and statistically reliable cytological markers for differentiating benign and malignant follicular thyroid neoplasms pre-operatively. METHODS: Cohesiveness of tumour cells in cytology slides from a series of 58 follicular tumours diagnosed between 1998 and 2004 inclusive was studied, including 48 follicular adenomas, and eight minimally invasive and two widely invasive follicular carcinomas. Photomicrographs of the cytology slides were taken and the digital images were analysed using computer image analysis software. We evaluated the relative proportions of cells arranged in groups of various sizes. The cohesiveness of the cells in cytological smears was then correlated with the immunohistochemical expression of E-cadherin in corresponding histological slides. RESULTS: Cases from 15 men (26%) and 43 women (74%) with a mean age of 50 years (range, 19-79) were analysed. In follicular adenomas and carcinomas, respectively, isolated cells were seen in 16.8% and 24.7% (P = 0.028), groups of two to five cells in 9.7% and 11.5% (P = 0.145) and groups of more than five cells in 73.5% and 63.8% (P = 0.041). The mean cell count in groups with more than five cells was 46.5 and 27.0 in adenomas and carcinomas, respectively (P < 0.001). Cell cohesiveness, either as percentage of cells in groups of more than five (R(2) = 0.026) or as mean cell count per group of more than five (R(2) = 0.005), was not found to be dependent on the expression of E-cadherin. Using a threshold of 13% isolated tumour cells in cytological smears, follicular adenomas and carcinomas could be distinguished with 90% sensitivity and 41% specificity. CONCLUSIONS: Although we demonstrated a statistically significant difference in cell cohesion between follicular adenomas and carcinomas, these could not be distinguished in the clinical setting by evaluation of the percentage of isolated cells in cytological smears because the specificity was too low. The absence of correlation of cellular cohesiveness with E-cadherin expression indicates that other factors are probably responsible for the loss of cohesiveness observed in follicular thyroid malignancy.

[Predictive diagnosis of breast cancer]. / Prediktivní diagnostika u karcinomu prsu.

Detection of selected predictive markers is currently included in the standard diagnostic algorithm of breast carcinoma specimens. Despite this fact we are facing several unresolved questions and issues. Probably the most frequently discussed predictive marker in breast carcinoma is HER-2/neu. The change of criteria of positivity in 2007 brought several confusions regarding the selection of patients eligible for anti-HER2 treatment. There is a deficiency of knowledge in tumors with the discordant phenotype (a discrepancy between the results of immunohistochemistry and in situ hybridization). Even in selected HER2 positive patients is the anti-HER2 treatment effective in only 30 % of cases. Thus, we evidently have to search for new markers which would help to more precisely select the optimal treatment for breast cancer patients.

[Predictive diagnosis of HER2 in gastric adenocarcinoma]. / Prediktivní diagnostika HER2 v adenokarcinomu zaludku.

Trastuzumab is a monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2). This receptor is overexpressed in approximately 20% of gastric adenocarcinomas. The overexpression is associated with a worse prognosis, but on the other hand, patients with HER2-positive cancers were shown to benefit from the addition of trastuzumab to standard chemotherapy. To begin the targeted therapy with trastuzumab, HER2 testing is now mandatory with immunohistochemistry being the primary test followed by in situ hybridization analysis of HER2 amplification in cases with equivocal immunopositivity (score 2+). The immunohistochemical HER2 scoring system has been modified to include incomplete basolateral and lateral membrane staining, and to differentiate between surgical and endoscopical samples of the tumor. Benefit from trastuzumab treatment can be expected in tumors showing an immunohistochemical score 3+, and in cases with score 2+ and a positive finding of HER2 amplification. Clinical trials with further monoclonal antibodies and receptor tyrosine kinase inhibitors are recently ongoing to broaden the spectrum of possibilities of a multitargeted approach to the treatment of gastric cancer.

Maternal and foetal outcomes in pregnant patients with active lupus nephritis.

The objective of this study was to determine the impact of lupus nephritis disease activity on maternal and foetal outcomes in pregnant patients with systemic lupus erythematosus (SLE). Medical records of all pregnant patients with SLE treated at our institution between 1976 and 2007 were reviewed. All patients met American College of Rheumatology classification criteria for SLE. Demographic data, history of lupus nephritis, nephritis disease activity and maternal and foetal outcomes of pregnancy were abstracted. Active lupus nephritis was defined as the presence of proteinuria >0.5 g/day and/or active urinary sediment with or without an elevation in serum creatinine (Cr). Quiescent lupus nephritis was confirmed in the presence of proteinuria <0.5 mg/day and inactive urinary sediment. We identified 58 patients with 90 pregnancies. Compared with pregnancies in SLE patients without renal involvement (n = 47), pregnancies in patients with active lupus nephritis (n = 23) were associated with a higher incidence of maternal complications (57% vs 11%, P < 0.001), whereas those with quiescent lupus nephritis (n = 20) were not (35% vs 11%, P = 0.10). Women with active lupus nephritis were more likely to deliver preterm than women without lupus nephritis, median of 34 weeks vs 40 gestational weeks, respectively (P = 0.002) and were more likely to suffer foetal loss (35% vs 9%, P = 0.031). Active, but not quiescent, lupus nephritis during pregnancy is associated with a higher incidence of maternal and foetal complications compared with pregnancies in SLE patients without renal involvement.