Streptococcus induces circulating CLA(+) memory T-cell-dependent epidermal cell activation in psoriasis.

Streptococcal throat infection is associated with a specific variant of psoriasis and with HLA-Cw6 expression. In this study, activation of circulating psoriatic cutaneous lymphocyte-associated antigen (CLA)(+) memory T cells cultured together with epidermal cells occurred only when streptococcal throat extracts were added. This triggered the production of Th1, Th17, and Th22 cytokines, as well as epidermal cell mediators (CXCL8, CXCL9, CXCL10, and CXCL11). Streptococcal extracts (SEs) did not induce any activation with either CLA(-) cells or memory T cells cultured together with epidermal cells from healthy subjects. Intradermal injection of activated culture supernatants into mouse skin induced epidermal hyperplasia. SEs also induced activation when we used epidermal cells from nonlesional skin of psoriatic patients with CLA(+) memory T cells. Significant correlations were found between SE induced upregulation of mRNA expression for ifn-γ, il-17, il-22, ip-10, and serum level of antistreptolysin O in psoriatic patients. This study demonstrates the direct involvement of streptococcal infection in pathological mechanisms of psoriasis, such as IL-17 production and epidermal cell activation.

A multicolor fluorescence in situ hybridization assay: A monitoring tool in the surveillance of patients with a history of non-muscle-invasive urothelial cell carcinoma: A prospective study.

BACKGROUND: Non-muscle-invasive urothelial cell carcinoma (NMIUCC) has a high tendency to recur and affected patients must be monitored regularly using invasive cystoscopies. The aim of the current study was to compare a multicolor fluorescence in situ hybridization (FISH) assay (UroVysion) with routine follow-up (cystoscopy and cytology) in the monitoring of patients with a previous history of NMIUCC. METHODS: An unselected cohort of patients under surveillance for a previous history of NMIUCC was prospectively studied. A total of 248 examinations in 223 patients were analyzed. Each exploration was comprised of cytological and FISH microscopic examination of voided urine samples and cystoscopy. The sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values for tumor recurrence of all 3 techniques were determined. RESULTS: The sensitivities of FISH and cystoscopy were not found to be significantly different (92.9% and 82.1%, respectively). The specificities of FISH and cystoscopy were 92.7% and 89.7%, respectively. The PPV and NPV of FISH were 53.5% and 97.2%, respectively, whereas those of cystoscopy were 63.4% and 98.9%, respectively. No significant differences were found between these 2 tests. In contrast, the sensitivity and specificity of cytology were 14.3% and 99.5%, respectively. CONCLUSIONS: Given the lack of statistically significant differences with regard to FISH and cystoscopy results, the authors propose that FISH could be a useful monitoring tool in the surveillance of patients with a previous history of NMIUCC.

Increased ALK gene copy number and amplification are frequent in non-small cell lung cancer.

INTRODUCTION: Translocation of the anaplastic lymphoma kinase (ALK) gene is involved in the tumorigenesis of a subset of non-small cell lung carcinomas (NSCLCs) and identifies patients sensitive to ALK inhibitors. ALK copy number changes and amplification, which plays an oncogenic role in tumors such as neuroblastoma, are poorly characterized in NSCLC. We aimed to study the prevalence of ALK copy number changes and their correlation to ALK protein expression, epidermal growth factor receptor (EGFR) status, and clinicopathological data in patients with NSCLC. METHODS: ALK status was evaluated by fluorescence in situ hybridization (FISH). Specimens with ALK translocation were studied for echinoderm microtubule-associated protein-like 4 (EML4), KIF5B, and TFG status. ALK expression was assessed by immunohistochemistry. EGFR gene and protein status were evaluated in adenocarcinomas. Survival analysis was performed. RESULTS: One hundred seven NSCLC cases were evaluated. There were two cases of EML4-ALK translocation and one with an atypical translocation of ALK. Both cases of EML4-ALK translocation had ALK protein expression, whereas in the rest, ALK was undetected. Eleven cases (10%) exhibited ALK amplification and 68 (63%) copy number gains. There was an association between ALK amplification and EGFR FISH positivity (p < 0.0001) but not with prognosis. In conclusion, EML4-ALK translocation is a rare event in NSCLC. CONCLUSION: The study reveals a significant frequency of ALK amplification and its association with EGFR FISH positivity in lung adenocarcinomas. Based on these findings, a potential role of ALK amplification in the response to ALK inhibitors alone or combined with EGFR inhibitors in NSCLC merits further studies.