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- Bertucci, F., et al.
(författare)
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The genomic grade index predicts postoperative clinical outcome in patients with soft-tissue sarcoma
- 2018
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 29:2, s. 459-465
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Tidskriftsartikel (refereegranskat)abstract
- Background: Soft-tissue sarcomas (STSs) are a group of rare, heterogeneous, and aggressive tumors, with high metastatic risk and relatively few efficient systemic therapies. We hypothesized that the Genomic Grade Index (GGI), a 108-gene signature previously developed in early-stage breast cancer, might improve the prognostic assessment of patients with early-stage STS. Patients and methods: We collected gene expression and clinicopathological data of 678 operated STS, and searched for correlations between the GGI-based classification and clinicopathological variables, including the metastasis-free survival (MFS). Results: Based on GGI, 275 samples (41%) were classified as 'GGI-low' and 403 (59%) as 'GGI-high'. The 'GGI-high' class was more associated with poor-prognosis features than the 'GGI-low' class: pathological grade 3 (P=9.50E-11), undifferentiated sarcomas and leiomyosarcomas (P<1.00E-06), location in extremities (P<1.00E-06), and complex genetic profile (P=2.1E-20). The 5-year MFS was 53% (95%CI 47-59) in the 'GGI-high' class versus 78% (95%CI 72-85) in the 'GGI-low' class (P=3.02E-11), with a corresponding hazard ratio for metastatic relapse equal to 2.92 (95%CI 2.10-4.07; P=2.23E-10). In multivariate analysis, the GGI-based classification remained significant, whereas the pathological grade did not. In fact, the GGI-based classification stratified the patients with pathological grades 1 and 2 and those with pathological grade 3 in two classes with different 5-year MFS. Comparison of the GGI and CINSARC multigene signatures revealed similar correlations with clinicopathological variables, which were, however, stronger with GGI than with CINSARC, a strong concordance (71%) in terms of low-risk or high-risk classifications, and independent prognostic value for MFS in multivariate analysis, suggesting complementary prognostic information. Conclusion: GGI refines the prediction of MFS in operated STS and might improve the tailoring of adjuvant chemotherapy. Further clinical validation is warranted in larger retrospective, then prospective series, as well as the functional validation of relevant genes that could provide new therapeutic targets.
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- Martin de la Fuente, L., et al.
(författare)
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Claudin-4 expression is associated with progression free survival in ovarian cancer, but not with chemotherapy response
- 2017
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Ingår i: International Journal of Gynecological Pathology. - 0277-1691. ; 37:2, s. 101-109
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Tidskriftsartikel (refereegranskat)abstract
- The tight junction protein claudin-4 has been reported to be overexpressed in advanced ovarian cancer. We investigated the prognostic significance of claudin-4 overexpression and whether claudin-4 expression could predict platinum response in primary ovarian carcinoma (OC). Claudin-4 expression was evaluated by immunohistochemistry in a tissue microarray of 140 OCs. Multivariable Cox-regression models were used to assess the effect of claudin-4 overexpression on progression-free survival and overall survival (OS). Kaplan-Meier survival analyses and the logrank test were performed comparing claudin-4 high and low groups. The association between claudin-4 expression and platinum resistance was assessed using risk ratios and the Pearson χ 2 test. A dataset of >1500 epithelial ovarian cancers was used to study the association between CLDN4 mRNA and survival. Of 140 evaluable cases, 71 (51%) displayed high claudin-4 expression. Claudin-4 overexpression predicted shorter 5-yr progression-free survival and OS in univariable analyses [hazard ratio (HR)=1.6 (1.1-2.5), P=0.020 and HR=1.6 (1.0-2.4), P=0.041, respectively]. Hazard of relapse was similar [HR=1.5 (1.0-2.4)] after adjustment for age, stage, type, and BRCA1/2 status in a multivariable analysis, but the evidence was slightly weaker (P=0.076). Validation in an external cohort confirmed the association between high expression of CLDN4 and poor 10-yr OS [HR=1.3 (1.1-1.5), P<0.001]. However, no confident association between claudin-4 and platinum sensitivity was found in our cohort [risk ratio=1.2 (0.7-2.0), P=0.3]. These findings suggest that high expression of claudin-4 may have a prognostic value in OC. The role of claudin-4 in the development of platinum resistance remains unclear.
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- Wild, CP, et al.
(författare)
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Cancer Prevention Europe
- 2019
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Ingår i: Molecular oncology. - : Wiley. - 1878-0261 .- 1574-7891. ; 13:3, s. 528-534
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Tidskriftsartikel (refereegranskat)
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- Lindberg, L. J., et al.
(författare)
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Risk of Synchronous and Metachronous Colorectal Cancer : Population-Based Estimates in Denmark with Focus on Non-Hereditary Cases Diagnosed After Age 50
- 2019
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Ingår i: Scandinavian Journal of Surgery. - : SAGE Publications. - 1457-4969 .- 1799-7267. ; 108:2, s. 152-158
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: The risk of synchronous and metachronous colorectal cancer is influenced by heritable and environmental factors. As a basis for comparative studies, we provide population-based estimates of synchronous and metachronous colorectal cancer with a focus on non-heritable cases. Material and Methods: Based on data from national Danish cancer registers, we estimated the proportion of synchronous colorectal cancer and the incidence rates and risks for metachronous colorectal cancer in 28,504 individuals, who developed 577 metachronous colorectal cancer above age 50. Results: Synchronous colorectal cancer was diagnosed in 1.3% of the cases. The risk of metachronous colorectal cancer was associated with sex, tumor location, and age with the strongest influence from the latter. The incidence rate ratios for metachronous colorectal cancer ranged from above 6 in patients below age 65 to <1–3.2 in patients above age 65. The absolute risk of metachronous colorectal cancer was ⩾10% in patients below age 65 and 1.0%–8.0% in patients above age 65. Conclusion: Individuals who develop sporadic, non-inherited colorectal cancer above age 50 are at a significantly increased risk of metachronous colorectal cancer with risk estimates that are strongly affected by age. This observation underscores the need for development of targeted surveillance in the most common clinical subset of colorectal cancer.
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- Nyström, H., et al.
(författare)
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Hypoxia-inducible factor 1a predicts recurrence in high-grade soft tissue sarcoma of extremities and trunk wall
- 2017
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Ingår i: Journal of Clinical Pathology. - : BMJ. - 0021-9746 .- 1472-4146. ; 70:10, s. 879-885
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Tidskriftsartikel (refereegranskat)abstract
- Background and aim Sarcomas are of mesenchymal origin and typically show abundant tumour stroma and presence of necrosis. In search for novel biomarkers for personalised therapy, we determined the prognostic impact of stromal markers, hypoxia and neovascularity in high-grade soft tissue leiomyosarcoma and pleomorphic undifferentiated sarcoma. Method We evaluated CD163, colony-stimulating factor (CSF)-1, CD16 and hypoxia-inducible factor 1 (HIF-1)a using immunohistochemical staining and assessed microvessel density using CD31 in 73 highgrade leiomyosarcomas and undifferentiated pleomorphic sarcomas of the extremities and the trunk wall. The results were correlated to metastasis-free and overall survival. Results Expression of HIF-1a was associated with the presence of necrosis and independently predicted shorter metastasis-free survival (HR 3.2, CI 1.4 to 7.0, p=0.004), whereas neither expression of the stromal markers CD163, CD16 and CSF-1 nor microvessel density was prognostically relevant in this series. Conclusions There is increasing evidence for the prognostic role of hypoxia in high-grade soft tissue sarcoma, and these data suggest that HIF-1a expression represents a candidate prognostic biomarker for clinical application in high-grade leiomyosarcoma and undifferentiated pleomorphic sarcoma.
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