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- De Lara, Shahin, 1966, et al.
(författare)
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The prognostic relevance of FOXA1 and Nestin expression in breast cancer metastases: a retrospective study of 164 cases during a 10-year period (2004-2014)
- 2019
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Ingår i: Bmc Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCurrent prognostic markers cannot adequately predict the clinical outcome of breast cancer patients. Therefore, additional biomarkers need to be included in routine immune panels. FOXA1 was a significant predictor of favorable outcome in primary breast cancer, while Nestin expression is preferentially found in triple-negative tumors with increased rate of nodal metastases, and reduced survival. No studies have investigated the prognostic value of FOXA1 and Nestin expression in breast cancer metastases.MethodsBreast cancer metastases (n=164) from various anatomical sites were retrospectively analyzed by immunohistochemistry for FOXA1, Nestin and GATA3 expression. Cox regression analysis assessed the prognostic value of FOXA1 and Nestin expression.ResultsIn breast cancer metastases, FOXA1 expression was associated with Nestin-negativity, GATA3-positivity, ER-positivity, HER2-positivity and non-triple-negative status (P<0.05). In contrast, Nestin expression was associated with FOXA1-negative, GATA3-negative, ER-negative, and triple-negative metastases (P<0.05). Univariate Cox regression analysis showed FOXA1 expression was predictive of overall survival (OS, P=0.00048) and metastasis-free survival (DMFS, P=0.0011), as well as, distant metastasis-free survival in ER-positive patients (P=0.036) and overall survival in ER-negative patients (P=0.024). Multivariate analysis confirmed the significance of FOXA1 for both survival endpoints in metastatic breast cancer patients (OS, P=0.0033; DMFS, P=0.015).ConclusionsIn our study, FOXA1 was expressed mostly in ER-positive breast cancer metastases. Expression of Nestin was related to triple-negative metastases, where brain was the most frequent metastatic site. These findings highlight the clinical utility of FOXA1 and Nestin expression and warrant their inclusion in routine immunohistochemical panels for breast carcinoma.
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| 2. |
- Engqvist, Hanna, 1985, et al.
(författare)
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Immunohistochemical validation of COL3A1, GPR158 and PITHD1 as prognostic biomarkers in early-stage ovarian carcinomasn
- 2019
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ovarian cancer is the main cause of gynecological cancer-associated death. However, 5- Methods: Here, we evaluated the prognostic role of 29 genes for early-stage (I and II) ovarian Results: We provide evidence of aberrant protein expression patterns for Collagen type III alpha 1 Conclusions: The novel biomarkers identified here may improve prognostication at the time of
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| 4. |
- Parris, Toshima Z, 1978, et al.
(författare)
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Additive effect of the AZGP1, PIP, S100A8, and UBE2C molecular biomarkers improves outcome prediction in breast carcinoma
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 134:7, s. 1617-1629
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Tidskriftsartikel (refereegranskat)abstract
- The deregulation of key cellular pathways is fundamental for the survival and expansion of neoplastic cells, which in turn can have a detrimental effect on patient outcome. To develop effective individualized cancer therapies, we need to have a better understanding of which cellular pathways are perturbed in a genetically defined subgroup of patients. Here, we validate the prognostic value of a 13-marker signature in independent gene expression microarray datasets (n = 1,141) and immunohistochemistry with full-faced FFPE samples (n = 71). The predictive performance of individual markers and panels containing multiple markers was assessed using Cox regression analysis. In the external gene expression dataset, six of the 13 genes (AZGP1, NME5, S100A8, SCUBE2, STC2, and UBE2C) retained their prognostic potential and were significantly associated with disease-free survival (P < 0.001). Protein analyses refined the signature to a four-marker panel (AZGP1, PIP, S100A8, and UBE2C) significantly correlated with cycling, high grade tumors and lower disease-specific survival rates. AZGP1 and PIP were found in significantly lower levels in invasive breast tissue compared with adjacent normal tissue, whereas elevated levels of S100A8 and UBE2C were observed. A predictive model containing the four-marker panel in conjunction with established clinical variables outperformed a model containing the clinical variables alone. Our findings suggest that deregulated AZGP1, PIP, S100A8, and UBE2C are critical for the aggressive breast cancer phenotype, which may be useful as novel therapeutic targets for drug development to complement established clinical variables. © 2013 Wiley Periodicals, Inc.
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| 5. |
- Parris, Toshima Z, 1978, et al.
(författare)
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Clinical relevance of breast cancer-related genes as potential biomarkers for oral squamous cell carcinoma
- 2014
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Squamous cell carcinoma of the oral cavity (OSCC) is a common cancer form with relatively low 5-year survival rates, due partially to late detection and lack of complementary molecular markers as targets for treatment. Molecular profiling of head and neck cancer has revealed biological similarities with basal-like breast and lung carcinoma. Recently, we showed that 16 genes were consistently altered in invasive breast tumors displaying varying degrees of aggressiveness. Methods: To extend our findings from breast cancer to another cancer type with similar characteristics, we performed an integrative analysis of transcriptomic and proteomic data to evaluate the prognostic significance of the 16 putative breast cancer-related biomarkers in OSCC using independent microarray datasets and immunohistochemistry. Predictive models for disease-specific (DSS) and/or overall survival (OS) were calculated for each marker using Cox proportional hazards models. Results: We found that CBX2, SCUBE2, and STK32B protein expression were associated with important clinicopathological features for OSCC (peritumoral inflammatory infiltration, metastatic spread to the cervical lymph nodes, and tumor size). Consequently, SCUBE2 and STK32B are involved in the hedgehog signaling pathway which plays a pivotal role in metastasis and angiogenesis in cancer. In addition, CNTNAP2 and S100A8 protein expression were correlated with DSS and OS, respectively. Conclusions: Taken together, these candidates and the hedgehog signaling pathway may be putative targets for drug development and clinical management of OSCC patients.
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| 6. |
- Parris, Toshima Z, 1978, et al.
(författare)
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Frequent MYC coamplification and DNA hypomethylation of multiple genes on 8q in 8p11-p12-amplified breast carcinomas
- 2014
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Ingår i: Oncogenesis. - : Springer Science and Business Media LLC. - 2157-9024. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Genetic and epigenetic (DNA methylation, histone modifications, microRNA expression) crosstalk promotes inactivation of tumor suppressor genes or activation of oncogenes by gene loss/hypermethylation or duplications/hypomethylation, respectively. The 8p11-p12 chromosomal region is a hotspot for genomic aberrations (chromosomal rearrangements, amplifications and deletions) in several cancer forms, including breast carcinoma where amplification has been associated with increased proliferation rates and reduced patient survival. Here, an integrative genomics screen (DNA copy number, transcriptional and DNA methylation profiling) performed in 229 primary invasive breast carcinomas identified substantial coamplification of the 8p11-p12 genomic region and the MYC oncogene (8q24.21), as well as aberrant methylation and transcriptional patterns for several genes spanning the 8q12.1-q24.22 genomic region (ENPP2, FABP5, IMPAD1, NDRG1, PLEKHF2, RRM2B, SQLE, TAF2, TATDN1, TRPS1, VPS13B). Taken together, our findings suggest that MYC activity and aberrant DNA methylation may also have a pivotal role in the aggressive tumor phenotype frequently observed in breast carcinomas harboring 8p11-p12 regional amplification.
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| 9. |
- Adamovic, Tatjana, 1974, et al.
(författare)
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Nonrandom pattern of chromosome aberrations in 17beta-estradiol-induced rat mammary tumors: indications of distinct pathways for tumor development.
- 2007
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Ingår i: Genes, chromosomes & cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 46:5, s. 459-69
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Tidskriftsartikel (refereegranskat)abstract
- Estrogens play an important role in breast cancer etiology and the ACI rat provides a novel animal model for defining the mechanisms through which estrogens contribute to mammary cancer development. In crossing experiments between the susceptible ACI strain and two resistant strains, COP (Copenhagen) and BN (Brown Norway), several quantitative trait loci (QTL) that affect development of 17beta-estradiol (E2)-induced mammary tumors have been defined. Using comparative genomic hybridization (CGH), we have analyzed cytogenetic aberrations in E2-induced mammary cancers and have found clear patterns of nonrandom chromosomal involvement. Approximately two thirds of the tumors exhibited copy number changes. Losses of rat chromosome 5 (RNO5) and RNO20 were particularly common, and it was found that these two aberrations often occurred together. A third recurrent aberration involving proximal gain and distal loss in RNO6 probably defined a distinct subgroup of tumors, since it never occurred in combination with RNO5 loss. Interestingly, QTL with powerful effects on mammary cancer development have been mapped to RNO5 and RNO6. These findings suggest that there were at least two genetic pathways to tumor formation in this rat model of E2-induced mammary cancer. By performing CGH on mammary tumors from ACI rats, F1 rats from crosses between the ACI and COP or BN strains and ACI.BN-Emca8 congenic rats, which carry the BN allele of the Emca8 QTL on RNO5 on the ACI genetic background, we were able to determine that the constitution of the germ line influences the pattern of chromosomal aberrations.
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| 10. |
- Adamovic, Tatjana, 1974, et al.
(författare)
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Oncogene amplification in the proximal part of chromosome 6 in rat endometrial adenocarcinoma as revealed by combined BAC/PAC FISH, chromosome painting, zoo-FISH, and allelotyping.
- 2005
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Ingår i: Genes, chromosomes & cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 44:2, s. 139-53
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Tidskriftsartikel (refereegranskat)abstract
- The inbred BDII rat is a valuable experimental model for the genetic analysis of endometrial adenocarcinoma (EAC). One common aberration detected by comparative genomic hybridization in rat EAC was gain/amplification affecting the proximal part of rat chromosome 6 (RNO6). We applied rat and mouse chromosome painting probes onto tumor cell metaphase preparations in order to detect and characterize gross RNO6 aberrations. In addition, the RNO6q11-q16 segment was analyzed by fluorescence in situ hybridization with probes representing 12 cancer-related genes in the region. The analysis revealed that seven tumors contained large RNO6-derived homogeneously staining regions (HSRs) in addition to several normal or near-normal RNO6 chromosomes. Five tumors (two of which also had HSRs) exhibited a selective increase of the RNO6q11-q16 segment, sometimes in conjunction with moderate amplification of one or a few genes. Most commonly, the amplification affected the region centered around band 6q16 and included the Mycn, Ddx1, and Rrm2 genes. A second region, centering around Slc8a1 and Xdh, also was affected by gene amplification but to a lesser extent. The aberrations in the proximal part of RNO6 were further analyzed using allelotyping of microsatellite markers in all tumors from animals that were heterozygous in the proximal RNO6 region. We could detect allelic imbalance (AI) in 12 of 20 informative tumors, 6 of which were in addition to those already analyzed by molecular cytogenetic methods as described. Our findings suggest that increase/amplification of genes in this chromosome region contribute to the development of this hormone-dependent tumor.
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