Prognostic value of ALK overexpression and molecular abnormalities in high-grade serous ovarian carcinoma.

BACKGROUND: ALK receptor tyrosine kinase (ALK) aberrations have an established role in pathogenesis of many neoplasms, but their clinical significance in high grade serous ovarian carcinoma (HGSOC) is unclear. OBJECTIVE: To analyse the frequency of ALK overexpression, molecular abnormalities of ALK, and their impact on the progression-free survival (PFS) and overall survival (OS) in HGSOC. METHODS: Protein expression was examined by immunohistochemistry (IHC) using three different clones of anti-ALK antibody. The presence of translocations was analysed using fluorescent in situ hybridization. Next-generation sequencing was used for studying the copy number variation, as well as point mutation and translocations involving other commonly rearranged genes. RESULTS: ALK overexpression was demonstrated in up to 52% of tumours, whereas ALK copy gains in 8.2%, with no clear impact on survival. ALK point mutations were identified in 13 tumours (8.9%), with 3 belonging to the class IV showing significantly better OS. A trend suggesting better PFS was also noticed in these cases. Additionally, three gene fusions were found: ERBB2-GRB7, PRKCA-BRCA1 and SND1-BRAF, none of which has been previously described in HGSOC. CONCLUSIONS: HGSOC harbouring activating ALK mutations might be associated with a better survival, while ALK overexpression and ALK amplification does not impact the prognosis.

Expression of Female Sex Hormone Receptors, Connective Tissue Growth Factor and HER2 in Gallbladder Cancer.

Gallbladder cancer (GBC) is a highly malignant tumor with poorly understood etiology. An insight into phenotypic features of this malignancy may add to the knowledge of its carcinogenesis and pave the way to new therapeutic approaches. We assessed the expression of female sex hormone receptors (ERα, ERß, PR), connective tissue growth factor (CTGF) and HER2 in GBC, and adjacent normal tissue (NT), and determined their prognostic impact. Immunohistochemical (IHC) expression of all biomarkers was performed in formalin-fixed, paraffin-embedded specimens in 60 Caucasian GBC patients (51 women and 9 men). ERß, cytoPR and CTGF expression were found in 89%, 27%, 91% of GBC, and in 63%, 87%, 100% of NT, respectively. No ERα expression was found in GBC and NT. Strong (3+) HER2 expression by IHC or HER2 amplification was seen in five GBC (10.4%). A positive correlation was found between HER2 and CTGF and ERß expression in GBC and matched NT. In the multivariate analysis, patient age >70 years, tumor size and ERß expression in GBC was highly predictive for OS (p = 0.003). The correlation between HER2, CTGF and ERß expression in GBC and NT may indicate the interaction of these pathways in physiological processes and gallbladder pathology.

Severe acute toxicity following gemcitabine administration: A report of four cases with cytidine deaminase polymorphisms evaluation.

Gemcitabine (GCB) is a pyrimidine antimetabolite widely used in various solid tumors as a single agent or as a component of multidrug regimens. In the majority of patients, GCB is well tolerated, however life-threatening complications occasionally occur. The current report presents four cases of severe acute toxicity, which included two that were fatal, following administration of GCB alone or in combination with cisplatin. Of the four cases, in one, a Naranjo Adverse Drug Reaction Probability Score was definite, in two, probable and in one possible. To determine the potential causes of these toxicities, polymorphic variants of cytidine deaminase, the primary enzyme involved in the hepatic metabolism of GCB, were assessed. The homogeneous c.435TT variant was detected in one patient and a heterozygotic c.435CT variant in two, one of whom additionally harbored a heterozygotic c.79AC variant.

Problems of diagnostic assessment in advanced pancreatic neuroendocrine neoplasm and treatment implications: a case report and literature review.

We are reporting a case of a 55-year-old woman who was diagnosed as having a non-functioning pancreatic neuroendocrine neoplasm (NF-PNEN), the World Health Organization (WHO) low grade (G1) with liver metastases. In the staging process the positron emission tomography - computed tomography with Fluorine-18-Fluorodeoxyglucose (F-FDG PET-CT) and spiral CT then the gallium-DOTA-octreotate positron emission tomography - computer tomography (68Ga-DOTATATE PET-CT) shown difference in burden of disease. In first line therapy, everolimus (Afinitor®, Novartis Pharma GmbH, Germany) at the oral dose of 10 mg once daily and octreotide long-acting release (Sandostatin LAR®) 30 mg i.m. every 4 weeks were administered. Then, due to disease progression - radioisotope therapy with b-emitter Yttrium-90 (9°Y). Based on this experience and on the review of the literature, we recommend that the discrepancy between the imaging studies could be due to heterogeneity of proliferation rate and somatostatin receptors (SSTR) expression within a primary PNEN and metastases. Therefore in such cases of advanced PNEN WHO G1 in the lack of response to everolimus and octreotide LAR administration isotope therapy without a prior chemotherapy should be considered as a palliative treatment according to ESMO Clinical Practice Guidelines and Polish Network of Neuroendocrine Tumors.