Given its central involvement in ERK/MAPK signalling, we hypothesised that TOPK overexpression is significantly related to KRAS and BRAF mutations, thereby implicating this gene in the poorer non-small-cell lung carcinoma outcome of patients, both in terms of prognosis and response to anti-EGFR therapies. The aim of our study was, first, to determine using two randomised subgroups (n=543 and n=501) whether TOPK expression leads to reproducible associations with clinicopathological features by immunohistochemistry (IHC) and, second, to determine according to KRAS and BRAF gene status the prognostic effect of TOPK on 222 sporadic and 71 Lynch syndrome-associated CRC patients, as well as the prognostic and predictive value of TOPK in 45 metastatic CRC patients treated with anti-EGFR agents, cetuximab and panitumumab.
Methods Patients Sporadic CRC patients (Groups 1 and 2) A total of 1420 primary pre-operatively untreated, unselected sporadic CRC patients treated at the University Hospital of Basel between 1987 and 1996 were included in this study. Haematoxylin and eosin-stained slides were retrospectively collected from the Institute of Pathology, University Hospital of Basel, the Institute of Clinical Pathology, Basel, Switzerland and from the Institute of Pathology, Stadtspital Triemli, Z��rich, Switzerland. Histopathological criteria were reviewed by an experienced gastrointestinal pathologist (LT) and included tumour diameter, pT and pN classification, grade of differentiation, histological subtype, presence of vessel invasion, tumour border configuration (pushing/expanding or infiltrating) and presence of peritumoural lymphocytic inflammation at the invasive tumour front (Jass et al, 1986).
Clinical data including patient age at diagnosis, tumour location and follow-up, local recurrence, distant metastasis and post-operative therapy were retrieved from the patient records, where available. Censored observations included patients who were alive at the last follow-up, those who died for reasons other than CRC or were lost to follow-up. Median survival time was 76 (95% CI 47�C137) months; median follow-up was 60.3 months. Lynch syndrome-associated CRC patients (Group 3) In all, 94 patients with genetically confirmed Lynch syndrome-associated CRC identified from the Swiss Cancer Registry were included in this study. Histopathological criteria were reviewed and included pT, pN, pM classifications and grade of differentiation.
Clinical data including patient age at diagnosis, tumour location and follow-up were retrieved from patient records. Censored observations included patients who were alive at last follow-up, those who died for reasons other than CRC or were lost to follow-up. Follow-up period ranged from 0 to 74 years Dacomitinib and median follow-up time was 7.1 years (95% CI 5.4�C8.7).
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