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

Bronchogene Zyste : eine seltene Diagnose bei retroperitonealer Raumforderung

BACKGROUND: Bronchogenic cysts are developmental abnormalities of the primitive foregut which typically occur in the lung. Subdiaphragmatic and, especially, retroperitoneal locations are rare. The histopathological definition consists of the presence of ciliated epithelium together with cartilage or bronchial mucous glands. CASE PRESENTATION: We report on a 49-year-old patient with the incidental finding of a large cystic mass between the diaphragm and the stomach. Imaging studies suggested an adrenal tumour. Surgical resection and postoperative follow-up were uneventful. Histological examination revealed the surprising diagnosis of a bronchogenic cyst. CONCLUSION: Bronchogenic cysts must be considered in the differential diagnosis of retroperitoneal cystic lesions. Regardless of being asymptomatic most of the time, surgical resection is recommended to obtain definitive histological diagnosis and avoid future complications

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

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

Heterogeneity of ERG expression in core needle biopsies of patients with early prostate cancer

Prostate cancer is a heterogeneous, frequently multifocal disease with a broad spectrum of clinical, pathologic, and molecular characteristics. The TMPRSS2-ERG gene rearrangement is highly specific for prostate cancer. We used immunohistochemistry as a surrogate marker of the TMPRSS2-ERG fusion to study the heterogeneity of ERG expression in 280 prostate core needle biopsy series from 256 patients with early prostate cancer defined as 3 or less positive cores with no more than 50% of cancer per biopsy and a Gleason score of 7 or lower (3 + 4). Among the 163 patients with 2 or 3 cancer-positive biopsies, we found a subset of 19 patients (11.7%) with heterogeneous ERG expression. Thirteen (68.4%) of these patients showed biopsies with distinct positive and negative ERG staining in separate cores. The remaining 6 patients showed a mixture of both positive and negative staining within 1 biopsy core. This was either caused by different cancer foci (n = 3) or by one single, ERG-heterogeneous cancer focus (n = 3) in 1 core. Furthermore, we observed a heterogeneous ERG staining pattern over time in 6 (2.3%) of the 256 patients, in biopsies taken at various time points. An interobserver study of 21 cases with 2 separate cancer foci revealed that heterogeneity of ERG status in different cancer foci can be suspected based on morphologic differences (κ = 0.44). We conclude that heterogeneity of ERG expression is detectable in 10% to 15% of core biopsies of early prostate cancer. Further studies are needed to explore the clinical impact of heterogeneous ERG status in this patient group. © 2013 Elsevier Inc. All rights reserved

Tumor infiltration by FcIγRIII (CD16)+ myeloid cells is associated with improved survival in patients with colorectal carcinoma

The prognostic significance of macrophage and natural killer (NK) cell infiltration in colorectal carcinoma (CRC) microenvironment is unclear. We investigated the CRC innate inflammatory infiltrate in over 1,600 CRC using two independent tissue microarrays and immunohistochemistry. Survival time was assessed using the Kaplan-Meier method and Cox proportional hazards regression analysis in a multivariable setting. Spearman&apos;s rank correlation tested the association between macrophage and lymphocyte infiltration. The Basel study included over 1,400 CRCs. The level of CD16+ cell infiltration correlated with that of CD3+ and CD8+ lymphocytes but not with NK cell infiltration. Patients with high CD16+ cell infiltration (score 2) survived longer than patients with low (score 1) infiltration (p = 0.008), while no survival difference between patients with score 1 or 2 for CD56+ (p = 0.264) or CD57+ cell (p = 0.583) infiltration was detected. CD16+ infiltrate was associated with improved survival even after adjusting for known prognostic factors including pT, pN, grade, vascular invasion, tumor growth and age [(p = 0.001: HR (95% CI) = 0.71 (0.6-0.9)]. These effects were independent from CD8+ lymphocyte infiltration [(p = 0.036: HR (95% CI) = 0.81 (0.7-0.9)] and presence of metastases [(p = 0.002: HR (95% CI) = 0.43 (0.3-0.7)]. Phenotypic studies identified CD16+ as CD45+CD33+CD11b+CD11c+ but CD64- HLA-DR-myeloid cells. Beneficial effects of CD16+ cell infiltration were independently validated by a study carried out at the University of Athens confirming that patients with CD16 score 2 survived longer than patients with score 1 CRCs (p = 0.011). Thus, CD16+ cell infiltration represents a novel favorable prognostic factor in CRC. © 2010 UICC

Intratumoural budding (ITB) in preoperative biopsies predicts the presence of lymph node and distant metastases in colon and rectal cancer patients

Background:In colorectal cancer (CRC), tumour budding at the invasion front is associated with lymph node (LN) and distant metastasis. Interestingly, tumour budding can also be detected in biopsies (intratumoural budding; ITB) and may have similar clinical importance. Here we investigate whether ITB in preoperative CRC biopsies can be translated into daily diagnostic practice.Methods:Preoperative biopsies from 133 CRC patients (no neoadjuvant therapy) underwent immunohistochemistry for pan-cytokeratin marker AE1/AE3. Across all biopsies for each patient, the densest region of buds at × 40 (high-power field; HPF) was identified and buds were counted.Results:A greater number of tumour buds in the biopsy was associated with pT stage (P=0.0143), LN metastasis (P=0.0007), lymphatic (P=0.0065) and venous vessel invasion (P=0.0318) and distant metastasis (cM1) (P=0.0013). Using logistic regression, a 'scale' was developed to estimate the probability of LN and distant metastasis using the number of tumour buds (e.g. 10 buds per HPF: 64% chance of LN metastasis; 30 buds per HPF: 86% chance). Inter-observer agreement for ITB was excellent (intraclass correlation coefficient: 0.813).Conclusion:Tumour budding can be assessed in the preoperative biopsy of CRC patients. It is practical, reproducible and predictive of LN and distant metastasis. Intratumoural budding qualifies for further investigation in the prospective setting