Prognostic and predictive value of TOPK stratified by KRAS and BRAF gene alterations in sporadic, hereditary and metastatic colorectal cancer patients

BACKGROUND: Our aim was to investigate the prognostic and predictive value of the oncogenic MAPKK-like protein T-cell-originated protein kinase (TOPK) stratified by KRAS and BRAF mutations in patients with sporadic, hereditary and metastatic colorectal cancer (CRC) treated with anti-EGFR therapy. METHODS: Immunohistochemistry (IHC) for TOPK was performed on four study groups. Group 1 included two subgroups of 543 and 501 sporadic CRC patients used to test the reliability of TOPK expression by IHC. In Group 2, representing an additional 222 sporadic CRCs, the prognostic effect of TOPK stratified by KRAS and BRAF was assessed. The prognostic effect of TOPK was further analysed in Group 3, representing 71 hereditary Lynch syndrome-associated CRC patients. In Group 4, the predictive and prognostic value of TOPK was analysed on 45 metastatic patients treated with cetuximab or panitumumab stratified by KRAS and BRAF gene status. RESULTS: In both sporadic CRC subgroups (Group 1), associations of diffuse TOPK expression with clinicopathological features were reproducible. Molecular analysis of sporadic CRCs in Group 2 showed that diffuse TOPK expression was associated with KRAS and BRAF mutations (p<0.001) and with poor outcome in patients with either mutation in univariate and multivariate analysis (P=0.017). In hereditary patients (Group 3), diffuse TOPK was linked to advanced pT stage. In metastatic patients treated with anti-EGFR therapy (Group 4), diffuse TOPK expression was linked to dismal outcome despite objective response to treatment (P=0.01). CONCLUSIONS: TOPK expression is an unfavourable prognostic indicator in sporadic patients with KRAS or BRAF mutations and also in patients with metastatic disease experiencing a response to anti-EGFR therapies. The inhibition of TOPK, which could benefit 30-40% of CRC patients, may represent a new avenue of investigation for targeted therapy

Energy cost of running, cycling and swimming in young triathletes of both sexes

Bunc V., Horcic J., Heller J., Formánek J. Energy cost of running, cycling and swimming in young triathletes of both sexes. In: Les Cahiers de l'INSEP, n°24, 1999. 2e Congrès international de triathlon de l’INSEP – 2nd INSEP international triathlon Congress pp. 301-305

Coût énergétique de la course à pied, du cyclisme et de la natation chez une population de jeunes triathlètes des deux sexes

Bunc V., Horcic J., Heller J., Formánek J. Coût énergétique de la course à pied, du cyclisme et de la natation chez une population de jeunes triathlètes des deux sexes. In: Les Cahiers de l'INSEP, n°24, 1999. 2e Congrès international de triathlon de l’INSEP – 2nd INSEP international triathlon Congress pp. 296-300

Kinetics of HR and La concentration in blood during a triathlon race in young triathletes

Horcic J., Bunc V., Heller J., Belska M., Formánek J. Kinetics of HR and La concentration in blood during a triathlon race in young triathletes. In: Les Cahiers de l'INSEP, n°24, 1999. 2e Congrès international de triathlon de l’INSEP – 2nd INSEP international triathlon Congress pp. 356-358

Profil physiologique de jeunes triathlètes tchèques

Bunc V., Heller J., Horcic J., Novotny J. Profil physiologique de jeunes triathlètes tchèques. In: Les Cahiers de l'INSEP, n°20, 1997. Un sport, deux enchaînements, trois disciplines : le triathlon. Actes du 1er symposium international de l'entraînement en triathlon. pp. 123-127

Cinétique de FC et de (La) au cours d'un triathlon chez de jeunes triathlètes

Horcic J., Bunc V., Heller J., Belska M., Formánek J. Cinétique de FC et de (La) au cours d'un triathlon chez de jeunes triathlètes. In: Les Cahiers de l'INSEP, n°24, 1999. 2e Congrès international de triathlon de l’INSEP – 2nd INSEP international triathlon Congress pp. 353-355

SalvGlandDx - a comprehensive salivary gland neoplasm specific next generation sequencing panel to facilitate diagnosis and identify therapeutic targets

Diagnosis of salivary gland neoplasms is often challenging due to their high morphological diversity and overlaps. Several recurrent molecular alterations have been described recently, which can serve as powerful diagnostic tools and potential therapeutic targets (e.g. NTRK or RET fusions). However, current sequential molecular testing can be expensive and time consuming. In order to facilitate the diagnosis of salivary gland neoplasms, we designed an all-in-one RNA-based next generation sequencing panel suitable for the detection of mutations, fusions and gene expression levels (including NR4A3) of 27 genes involved in salivary gland neoplasms. Here we present the validation of the "SalvGlandDx" panel on FFPE histological specimen including fine needle aspiration (FNA) cell block material, against the standard methods currently used at our institution. In a second part we describe selected unique cases in which the SalvGlandDx panel allowed proper diagnosis and new insights into special molecular characteristics of selected salivary gland tumors. We characterize a unique salivary gland adenocarcinoma harboring a ZCCHC7-NTRK2 fusion, a highly uncommon spindle cell and pseudoangiomatoid adenoid-cystic carcinoma with MYBL1-NFIB fusion, and a purely oncocytic mucoepidermoid carcinoma, whereas diagnosis could be made by detection of a CRTC3-MAML2 rearrangement on the cell block specimen of the FNA. Further, a rare case of a SS18-ZBTB7A rearranged low-grade adenocarcinoma previously described as potential spectrum of microsecretory adenocarcinoma, is reported. In addition, features of six cases within the spectrum of polymorphous adenocarcinoma / cribriform adenocarcinoma of salivary gland including PRKD1 p.E710D mutations and novel fusions involving PRKAR2A-PRKD1, SNX9-PRKD1 and ATL2-PRKD3, are described