Monika Jurkowska

Clinical utility of the new American Joint Committee on Cancer staging system for gastrointestinal stromal tumors: current overall survival after primary tumor resection.

The objectives of the current study were to assess the reliability of the new revision of the American Joint Committee on Cancer (AJCC) staging system for gastrointestinal stromal tumors (GISTs) based on the National Comprehensive Cancer Network‐Armed Forces Institute of Pathology risk classification and to analyze the factors that influence after resection for primary GISTs in 2 AJCC groups: patients with GISTs originating from the stomach and omentum (G‐GISTs) and patients with other primary GISTs located mainly in the small bowel (nongastric GISTs [NG‐GISTs]).

Molecular alterations in clinical stage III cutaneous melanoma: Correlation with clinicopathological features and patient outcome

The aim of the present study was to evaluate the frequency and type of oncogenic v-raf murine sarcoma viral oncogene homolog B1 (BRAF)/neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) mutations in cutaneous melanoma with clinically detected nodal metastases (stage IIIB and C) in relation to clinicopathological features and outcome. The clinicopathological data of 250 patients following therapeutic lymphadenectomy (LND) between 1995 and 2010, as well as BRAF/NRAS mutational status in corresponding nodal metastases, were analyzed. The median follow-up time was 53 months. BRAF mutations were detected in 154 (62%) cases (141 p.V600E, nine p.V600K and four others) and mutually exclusive NRAS mutations were detected in 42 (17%) cases. The presence of a BRAF mutation was found to correlate with patients of a younger age. The five-year overall survival (OS) rate was 33 and 43% for LND and primary tumor excision, respectively, and the five-year disease-free survival (DFS) rate for LND was 25%. No correlation was identified between BRAF/NRAS mutational status and RFS or OS (calculated from the date of the LND and primary tumor excision); for BRAF- and NRAS-mutated melanoma, the prognosis was the same for patients with wild-type (WT) melanoma. The important factors which had a negative impact on OS and DFS were as follows: Male gender, >1 metastatic lymph node and extracapsular extension of nodal metastases. The interval between the diagnosis of the initial melanoma to regional nodal metastasis (median, 10 months) was not significantly different between BRAF-mutant and -WT patients. Our largest comprehensive molecular analysis of clinical stage III melanoma revealed that BRAF and NRAS mutational status is not a prognostic marker in stage III melanoma patients with macroscopic nodal involvement, but may have implications for potential adjuvant therapy.

Downstream and Intermediate Interactions of Synovial Sarcoma-Associated Fusion Oncoproteins and Their Implication for Targeted Therapy

Synovial sarcoma (SS), an aggressive type of soft tissue tumor, occurs mostly in adolescents and young adults. The origin and molecular mechanism of the development of SS remain only partially known. Over 90% of SS cases are characterized by the t(X;18)(p11.2;q11.2) translocation, which results mainly in the formation of SS18-SSX1 or SS18-SSX2 fusion genes. In recent years, several reports describing direct and indirect interactions of SS18-SSX1/SSX2 oncoproteins have been published. These reports suggest that the fusion proteins particularly affect the cell growth, cell proliferation, TP53 pathway, and chromatin remodeling mechanisms, contributing to SS oncogenesis. Additional research efforts are required to fully explore the protein-protein interactions of SS18-SSX oncoproteins and the pathways that are regulated by these partnerships for the development of effective targeted therapy.

Predictive Factors of Efficacy of Sunitinib Therapy in Gastrointestinal Stromal Tumours

Until the introduction of tyrosine kinase inhibitors, only limited treatment options were available for advanced/inoperable gastrointestinal stromal tumours (GISTs), the most common mesenchymal tumours of the gastrointestinal tract. Initially, it was imatinib mesylate that revolutionised patient outcomes in advanced cases, followed by sunitinib malate when the activity of imatinib turned out to be time-limited. There is substantial heterogeneity between GISTs in terms of response to targeted therapy. As was the case for imatinib, the efficacy of sunitinib depends on the primary tumour’s KIT/PDGFRA (platelet-derived growth factor receptor-alpha) genotype and on secondary mutations emerging during treatment. Interestingly, sunitinib-related adverse effects, such as arterial hypertension, may serve as biomarkers of the antitumour efficacy of the drug. Here we discuss possible mechanisms underlying these phenomena as well as data from our recently published study – the first to investigate the clinicopathologic and genetic characteristics associated with the results of sunitinib therapy in a large group of patients treated in routine clinical practice.