Respective Prognostic Value of Genomic Grade and Histological Proliferation Markers in Early Stage (pN0) Breast Carcinoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE48064 | GEO | 2014/02/18
SECONDARY ACCESSION(S): PRJNA209040
REPOSITORIES: GEO
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Project description:Phenotypic and genomic characterization of Early Stage Breast Carcinoma using Training set (n=109) Validation set (n=105) of SNP6 arrays Affymetrix SNP6.0 arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved breast tumoral samples.
2014-02-18 | E-GEOD-48064 | biostudies-arrayexpress
Project description:BackgroundGenomic grade (GG) is a 97-gene signature which improves the accuracy and prognostic value of histological grade (HG) in invasive breast carcinoma. Since most of the genes included in the GG are involved in cell proliferation, we performed a retrospective study to compare the prognostic value of GG, Mitotic Index and Ki67 score.MethodsA series of 163 consecutive breast cancers was retained (pT1-2, pN0, pM0, 10-yr follow-up). GG was computed using MapQuant Dx(R).ResultsGG was low (GG-1) in 48%, high (GG-3) in 31% and equivocal in 21% of cases. For HG-2 tumors, 50% were classified as GG-1, 18% as GG-3 whereas 31% remained equivocal. In a subgroup of 132 ER+/HER2- tumors GG was the most significant prognostic factor in multivariate Cox regression analysis adjusted for age and tumor size (HR = 5.23, p = 0.02).ConclusionsIn a reference comprehensive cancer center setting, compared to histological grade, GG added significant information on cell proliferation in breast cancers. In patients with HG-2 carcinoma, applying the GG to guide the treatment scheme could lead to a reduction in adjuvant therapy prescription. However, based on the results observed and considering (i) the relatively close prognostic values of GG and Ki67, (ii) the reclassification of about 30% of HG-2 tumors as Equivocal GG and (iii) the economical and technical requirements of the MapQuant micro-array GG test, the availability in the near future of a PCR-based Genomic Grade test with improved performances may lead to an introduction in clinical routine of this test for histological grade 2, ER positive, HER2 negative breast carcinoma.
| S-EPMC3329444 | biostudies-literature
Project description:Various histologic classification systems have been proposed as prognostic factors for gastric cancer. We assessed the prognostic value of Goseki classification as well as the TNM staging system, histological tumour grading, Lauren, WHO, Goseki and Siewert classifications in 100 patients with cardia carcinoma undergoing curative surgery. Two patients were lost at follow-up. The median time of follow-up in the remaining patients was 32.9 months after surgery (range: 0.1-142.1 months). No differences in survival rates were observed according to tumour grading, Lauren or WHO histologic or Siewert topographical classification. No differences were found according to Goseki classes, when considering either the mucin content of the carcinoma (types I and III vs II and IV) or the differentiation grade (types I and II vs III and IV). Multivariate analysis showed that the only lymph node positivity was a significant predictor of survival: 7.2% of patients with, but 41.5% of those without nodal involvement were alive after five years (P=0.0001). In conclusion, we found no prognostic role for Goseki or the traditional histological indexes, while the TNM staging system and particularly lymph node positivity were the main predictors of survival in patients with cardia adenocarcinoma.
| S-EPMC2747543 | biostudies-other
Project description:BackgroundIsocitrate dehydrogenase (IDH) wildtype (wt) grade II gliomas are a rare and heterogeneous entity. Survival and prognostic factors are poorly defined.MethodsWe searched retrospectively all patients diagnosed with diffuse World Health Organization (WHO) grades II and III gliomas at our center (1989-2020).ResultsOut of 517 grade II gliomas, 47 were "diffuse astrocytomas, IDHwt." Tumors frequently had fronto-temporo-insular location (28/47, 60%) and infiltrative behavior. We found telomerase reverse transcriptase (TERT) promoter mutations (23/45, 51%), whole chromosome 7 gains (10/37, 27%), whole chromosome 10 losses (10/41, 24%), and EGFR amplifications (4/43, 9%), but no TP53 mutations (0/22, 0%). Median overall survival (OS) was 59 months (vs 19 mo for IDHwt grade III gliomas) (P < 0.0001). Twenty-nine patients (29/43, 67%) met the definition of molecular glioblastoma according to cIMPACT-NOW update 3. Median OS in this subset was 42 months, which was shorter compared with patients with IDHwt grade II gliomas not meeting this definition (median OS: 57 mo), but substantially longer compared with IDHwt grade III gliomas meeting the definition for molecular glioblastoma (median OS: 17 mo, P < 0.0001). Most patients with IDHwt grade II gliomas met cIMPACT criteria because of isolated TERT promoter mutations (16/26, 62%), which were not predictive of poor outcome (median OS: 88 mo). Actionable targets, including 5 gene fusions involving FGFR3, were found in 7 patients (24%).ConclusionsOur findings highlight the importance of histological grading and molecular profiling for the prognostic stratification of IDHwt gliomas and suggest some caution when assimilating IDHwt grade II gliomas to molecular glioblastomas, especially those with isolated TERT promoter mutation.
| S-EPMC8168809 | biostudies-literature
Project description:BackgroundWhile molecular insights to diffuse lower-grade glioma (dLGG) have improved the basis for prognostication, most established clinical prognostic factors come from the pre-molecular era. For instance, WHO grade as a predictor for survival in dLGG with isocitrate dehydrogenase (IDH) mutation has recently been questioned. We studied the prognostic role of WHO grade in molecularly defined subgroups and evaluated earlier used prognostic factors in the current molecular setting.Material and methodsA total of 253 adults with morphological dLGG, consecutively included between 2007 and 2018, were assessed. IDH mutations, codeletion of chromosomal arms 1p/19q, and cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletions were analyzed.ResultsThere was no survival benefit for patients with WHO grade 2 over grade 3 IDH-mut dLGG after exclusion of tumors with known CDKN2A/B homozygous deletion (n=157) (log-rank p=0.97). This was true also after stratification for oncological postoperative treatment and when astrocytomas and oligodendrogliomas were analyzed separately. In IDH-mut astrocytomas, residual tumor volume after surgery was an independent prognostic factor for survival (HR 1.02; 95% CI 1.01-1.03; p=0.003), but not in oligodendrogliomas (HR 1.02; 95% CI 1.00-1.03; p=0.15). Preoperative tumor size was an independent predictor in both astrocytomas (HR 1.03; 95% CI 1.00-1.05; p=0.02) and oligodendrogliomas (HR 1.05; 95% CI 1.01-1.09; p=0.01). Age was not a significant prognostic factor in multivariable analyses (astrocytomas p=0.64, oligodendrogliomas p=0.08).ConclusionOur findings suggest that WHO grade is not a robust prognostic factor in molecularly well-defined dLGG. Preoperative tumor size remained a prognostic factor in both IDH-mut astrocytomas and oligodendrogliomas in our cohort, whereas residual tumor volume predicted prognosis in IDH-mut astrocytomas only. The age cutoffs for determining high risk in patients with IDH-mut dLGG from the pre-molecular era are not supported by our results.
| S-EPMC8785215 | biostudies-literature
Project description:The differentiation status of tumor cells, defined by histomorphological criteria, is a prognostic factor for survival of patients affected with intrahepatic cholangiocarcinoma (ICC). To strengthen the value of morphological differentiation criteria, we wished to correlate histopathological differentiation grade with expression of molecular biliary differentiation markers and of microRNAs previously shown to be dysregulated in ICC. We analysed a series of tumors that were histologically classified as well, moderately or poorly differentiated, and investigated the expression of cytokeratin 7, 19 and 903 (CK7, CK19, CK903), SRY-related HMG box transcription factors 4 and 9 (SOX4, SOX9), osteopontin (OPN), Hepatocyte Nuclear Factor-1 beta (HNF1?), Yes-associated protein (YAP), Epithelial cell adhesion molecule (EPCAM), Mucin 1 (MUC1) and N-cadherin (NCAD) by qRT-PCR and immunostaining, and of miR-31, miR-135b, miR-132, miR-200c, miR-221 and miR-222. Unexpectedly, except for subcellular location of SOX9 and OPN, no correlation was found between the expression levels of these molecular markers and histopathological differentiation grade. Therefore, our data point toward necessary caution when investigating the evolution and prognosis of ICC on the basis of cell differentiation criteria.
| S-EPMC4900546 | biostudies-literature
Project description:Canine mammary carcinoma represents a model for the study of human breast cancer, although the prognostic value of various clinical, histological and immunohistochemical parameters has shown contradictory results. A prospective study, through a 4-year follow-up, was performed in 77 patients with mammary carcinoma to analyse the association between histological diagnosis, grade of malignancy, peritumoral and vascular invasion. We have also performed immunohistochemistry for the expression of oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and cyclooxygenase-2 (COX-2) that define human biomarkers of disease progression and treatment response. An association between histological diagnosis and clinical stage was observed with a high proportion of complex carcinoma classified as stage I. There was a higher proportion of ER+ /PR+ /HER2- tumours in stage I. In contrast, triple-negative tumours (ER- /PR- /HER2- ) were found mainly in advanced clinical stages and were associated with vascular and peritumoral invasion. The tumours included in group VII (carcinosarcoma/adenosquamous carcinoma/other special types of carcinoma) had a higher expression of COX-2. The univariate analysis showed that those patients with complex carcinoma had the lowest incidence of metastases and the highest probability of survival. In contrast, a high proportion of patients with anaplastic/inflammatory carcinoma developed metastases and showed the lowest probability of survival. In addition, the estimated survival time was shorter for those patients with triple-negative tumours and those with high COX-2 expression. However, in the multivariate analysis, only the peritumoral invasion maintained its prognostic significance. In conclusion, in our study anaplastic/inflammatory carcinomas had the worst prognosis with a high proportion of triple-negative tumours in this category.
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Project description:The A disintegrin and metalloproteinase 9 (ADAM9) protein has been suggested to promote carcinoma invasion and appears to be overexpressed in various human cancers. However, its role has rarely been investigated in gliomas and, thus, in the current study we have evaluated ADAM9 expression in gliomas and examined the relevance of its expression in the prognosis of glioma patients. Clinical characteristics, RNA sequence data, and the case follow-ups were reviewed for 303 patients who had histological, confirmed gliomas. The ADAM9 expression between lower-grade glioma (LGG) and glioblastoma (GBM) patients was compared and its association with progression-free survival (PFS) and overall survival (OS) was assessed to evaluate its prognostic value. Our data suggested that GBM patients had significantly higher expression of ADAM9 in comparison to LGG patients (p < 0.001, t-test). In addition, among the LGG patients, aggressive astrocytic tumors displayed significantly higher ADAM9 expression than oligodendroglial tumors (p < 0.001, t-test). Moreover, high ADAM9 expression also correlated with poor clinical outcome (p < 0.001 and p < 0.001, log-rank test, for PFS and OS, respectively) in LGG patients. Further, multivariate analysis suggested ADAM9 expression to be an independent marker of poor survival (p = 0.002 and p = 0.003, for PFS and OS, respectively). These results suggest that ADAM9 mRNA expression is associated with tumor grade and histological type in gliomas and can serve as an independent prognostic factor, specifically in LGG patients.
| S-EPMC5037653 | biostudies-literature
Project description:Canine Mast cell tumors (MCTs) constitute approximately 21% of all canine skin tumors. Despite the use of comprehensive grading systems, biological aggressiveness is sometimes difficult to predict, therefore there is a need for better prognostic markers. Progression in various cancers involves DNA hypermethylation, hypomethylation and epigenetic enzyme dysregulation. Therefore, global levels of 5-methylcytosine, 5-hydroxymethylcytosine and associated enzymes DNMT1, and IDH1 expression may predict MCT aggressiveness. A tissue microarray (TMA) with cores from 244 different tumor samples from 189 dogs was immunolabelled and used to quantify the global DNA methylation and hydroxymethylation levels as well as the levels of the enzymes involved in DNA methylation and their relationship with canine MCT outcome. From the immunolabelled TMA, H-scores were generated using QuPath (v0.1.2) and analyzed with associated patient data. High 5MC and DNMT1, and low IDH1 levels were associated with poorer outcome when looking at all canine MCT cases. High 5MC levels showed significance for shorter disease-free interval (DFI) in subcutaneous cases and high 5MC levels showed poorer DFI and overall survival (OS) in cases with Kiupel's grading system high grade. Cases with grade II in Patnaik's grading system showed better DFI with low levels of DNMT1 and better OS with low levels of 5MC and 5HMC. High levels of DNMT1 staining were also associated with shorter DFI for dermal MCTs. For cases that received adjuvant therapy in addition to surgery, all parameters except IDH1 were significantly associated with OS. Therefore, there is potential for DNA methylation status and levels of enzymes associated with DNA methylation pathways to better predict outcome in canine MCT, and to possibly influence treatment decisions.
| S-EPMC10062589 | biostudies-literature
Project description:We used Targeted RNA-seq to generate a gene expression data set of the 72-gene panel (TARGETSEQ) including 483 targeted RNA-seq data of 225 breast cancer FFPE samples from Shanghai and 258 breast cancer FFPE samples from UNC at Chapel Hill. The identified gene panel and risk evaluation model iRDM were developed in training data set AFFY1951 (p<0.0001, n=1951) and further validated in two other published gene expression datasets including Illumina beads array data METABRIC (p<0.0001, n=1997) and whole transcriptomic mRNA-seq data TCGA (p=0.00019, n=996) and in our own targeted RNA-seq data TARGETSEQ (p<0.0001, n=303) (of 483 RNA-seq samples, 303 with survival data). In conclusion, immunity gene expression were an important parameter for prognosis and therefore can be incorporated into current multi-gene assays to improve assessment of risk of distant metastasis in breast cancer.
2018-10-01 | GSE113863 | GEO