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Inter-test concordance between the MammaPrint and the EndoPredict tests used to predict the risk of recurrence in breast cancer was evaluated in 94 oestrogen receptor-positive, HER2-negative breast cancers. We correlated histopathological data with clinical risk estimation as defined in the MINDACT trial. 42.6% (40/94) of cases were high-risk by MammaPrint, 44.7% (42/94) by EndoPredict (EPclin), and 45.7% (43/94) by clinical risk definition. Thirty-six percent of genomic risk predictions were discordant with a low inter-test correlation between EndoPredict and MammaPrint (p = 0.012; κ = 0.27, 95% CI [0.069, 0.46]). Clinical risk stratification did not correlate with MammaPrint (p = 0.476) but highly correlated with EndoPredict (p < 0.001). Consequently, clinically high-risk tumours (n = 43) were more frequently high-risk by EndoPredict than by MammaPrint (76.6% vs. 46.5%, p = 0.004), with 44% of cases discordantly classified and no significant association between genomic risk predictions (p = 0.294). Clinicians need to be aware that clinical pre-stratification can profoundly influence multigenomic test performance. [ABSTRACT FROM AUTHOR]

Two major reasons compel us to study tumour heterogeneity: firstly, it represents the basis of acquired therapy resistance, and secondly, it may be one of the major sources of the low level of reproducibility in clinical cancer research. The present review focuses on the heterogeneity of neoplastic disease, both within the primary tumour and between primary tumour and metastases. We discuss different levels of heterogeneity and the current understanding of the phenomenon, as well as imminent developments relevant for clinical research and diagnostic pathology. It is necessary to develop new tools to study heterogeneity and new biomarkers for heterogeneity. Established and new in situ methods will be very useful. In future studies, not only clonal heterogeneity needs to be addressed but also non-clonal phenotypic heterogeneity which might be important for therapy resistance. We also review heterogeneity established in major tumour types, in order to explore potential similarities that might help to define new strategies for targeted therapy. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. The vast majority demonstrates mutually exclusive KIT or PDGFRA gain-of-function mutations. KIT or PDGFRA mutation is an early event in GIST pathogenesis and development, and has led to the introduction of KIT and PDGFRA kinase inhibitors in GIST, which has tremendously changed survival of patients suffering from this disease. Approximately 85 % of pediatric GISTs and 10-15 % of adult GISTs are devoid of mutations in the KIT and PDGFRA genes and are referred to as wild-type GISTs (WT-GIST). Over the past years, it has been shown that WT-GISTs are profoundly different from mutant GIST with regard to their clinical behavior as well as their molecular profile, and are now considered a separate pathological entity. Based on their significant molecular and clinical heterogeneity, WT-GISTs should be considered a group of diseases rather than a single disease entity. The following short review will exclusively focus on WT-GISTs, a group of tumors traditionally divided into a syndromic and a nonsyndromic (sporadic) subgroup. In addition, immunohistochemical expression of succinate dehydrogenase B (SDHB) has recently been introduced to subtype WT-GISTs into an SDHB-positive (proficient) from SDHB-negative (deficient) group. [ABSTRACT FROM AUTHOR]