Different topoisomerase IIa protein expression patterns affect prognosis in tongue squamous cell carcinoma: A quantitative digital image analysis study

Aim: Topoisomerases represent a class of nucleic enzymes involved in the DNA replication, transcription and also chromosome topological formation. Topoisomerase IIa (Topo Iia - gene location 17q21) inhibition promotes cell death and for this reason, it is a target for specific chemotherapy (anthracyclines, podophyllotoxines). Our aim was to investigate the potential prognostic significance of its protein expression in squamous cell carcinomas of the tongue (TSCCs) based on a quantitative, digital image analysis method. Materials and methods: We analysed immunohistochemically eighty-seven (n = 87) archival, primary TSCCs using a monoclonal anti-Topo IIa antibody. A computerised image analysis assay was applied for the evaluation of the results [nuclear labellingindex(NLI)]. Survival analysiswasalso performed. Results: Topo IIa protein was overexpressed in 48/87 (55.1%) cases. High NLI values were detected in 17/48 (35.4%), whereas moderate levels of expression were detected in 31/48 (64.6%) cases. Statistical significance was not assessed correlating overall protein expression to grade or stage of the examined tumours (P = 0.88, P = 0.73, respectively), but only to the anatomical region (P = 0.04). Cox regression analysis showed that Topo IIa and also the size of the tumours were strongly associated to the survival of the patients (P = 0.01, P = 0.02, respectively). Conclusions: Topo IIa protein overexpression is a frequent event in TSCCs. Topo IIa may be used as a prognostic factor and also as a basis for targeted chemotherapy strategies in TSCCs. Furthermore, digital image analysis improves the quantification of immunohistochemical stains in an accurate and fast way. © 2008 The Authors. Journal compilation © 2008 Blackwell Munksgaard

Chromogenic in situ hybridization analysis of epidermal growth factor receptor gene/chromosome 7 numerical aberrations in hepatocellular carcinoma based on tissue microarrays

Although Epidermal Growth Factor Receptor (EGFR) overexpression is observed frequently in hepatocellular carcinomas (HCC), specific gene deregulation mechanisms remain unknown. Our aim was to investigate the prognostic significance of the combined protein and gene/chromosome 7 numerical alterations. Using tissue microarray technology, thirty-five (n=35) paraffin embedded histologically confirmed HCCs were cored and re-embedded in a paraffin block. Immunohistochemistry was performed for the determination of EGFR protein levels and evaluated by the performance of digital image analysis. Chromogenic in situ hybridization was also performed based on the use of EGFR gene and chromosome 7 centromeric probes, respectively. EGFR overexpression was observed in 26/35 (74.2%) cases and was correlated to the grade of the tumors and also to the history of the patients (p=0.013, p=0.036, respectively). Numerical alterations regarding gene and chromosome 7 were identified in 4/35 (11.4%) and 12/35 (43.2%) cases associated to the grade of the tumors (p=0.019, p=0.001, respectively) and to the survival rate of the patients (p=0.037, p=0.001, respectively). EGFR overall expression was also correlated to the gene copies (p=0.020). EGFR gene numerical alterations -although rare- and also chromosome 7 aneuploidy maybe affect prognosis in HCC patients. To our knowledge this is the first chromogenic in situ hybridization analysis based on tissue microarrays in hepatocellular carcinoma. © 2009 Arányi Lajos Foundation

Treatment of Bing-Neel syndrome with first line sequential chemoimmunotherapy: A case report

RATIONALE: Bing-Neel syndrome (BNS) is a rare manifestation of Waldenström macroglobulinemia (WM) with <200 cases reported in the literature. Herein, we describe a case of newly diagnosed BNS treated with a novel therapeutic strategy. PATIENT CONCERNS: A 67-year-old woman diagnosed with asymptomatic WM 3 years ago presented with gradual vision deterioration the past 3 months. Ophthalmologic examination revealed bilateral reduction in visual acuity (7/10) and bilateral optic disc swelling which was more prominent in the left eye. DIAGNOSES: Brain imaging revealed bilateral swelling of optic nerves extending from the retina to the optic chiasm and swelling of the left optic tract. Patchy enhancement of optic nerves was also shown upon intravenous contrast administration. Flow cytometry of the cerebrospinal fluid (CSF) revealed the presence of κ-light chain restricted, monoclonal B-lymphocytes. CSF protein electrophoresis showed a monoclonal band in the gamma region and immunofixation was positive for immunoglobulin M and kappa light chain. Thus, the diagnosis of BNS was established. INTERVENTIONS: The patient was initially treated with intrathecal methotrexate and systemic chemotherapy. Following 2 intrathecal methotrexate infusions, CSF flow cytometry did not detect any cells, whereas the patient reported improvement in visual acuity. Therefore, we opted to start maintenance treatment with IV rituximab and per os ibrutinib. OUTCOMES: Following 1 year posttreatment initiation, visual problems have resolved completely and the patient remains on hematologic and imaging complete response. LESSONS: We propose a novel sequential chemoimmunotherapy approach for BNS treatment aiming both at rapid disease control and deep and durable remission with minimization of induced toxicity