scholarly journals Protein Analysis of Glioblastoma Primary and Posttreatment Pairs Suggests a Mesenchymal Shift at Recurrence

2016 ◽  
Vol 75 (10) ◽  
pp. 925-935 ◽  
Author(s):  
Matthew D Wood ◽  
Gerald F Reis ◽  
David E Reuss ◽  
Joanna J Phillips
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Gene Expression Pattern ◽  
Tissue Microarrays ◽  
Poor Correlation ◽  
Ki 67 ◽  
Mesenchymal Phenotype ◽  
Idh1 R132h ◽  
Recurrent Tumors ◽  
Phosphorylated Stat3

Abstract Glioblastomas (GBM) are aggressive brain tumors that inevitably recur despite surgical resection, chemotherapy, and radiation. The degree to which recurrent GBM retains its initial immunophenotype is incompletely understood. We generated tissue microarrays of paired initial and posttreatment GBM (3 pairs positive and 17 negative for IDH1 R132H ) from the same patients and made comparisons in the IDH1 R132H -negative group for immunohistochemical and gene expression differences between primary and recurrent tumors. In initial tumors, immunopositivity for Ki-67 in > 20% of tumor cells was associated with shorter progression-free and overall survival. Recurrent tumors showed decreased staining for CD34 suggesting lower vessel density. A subset of tumors showed increased staining for markers associated with the mesenchymal gene expression pattern, including CD44, phosphorylated STAT3, and YKL40. Recurrent tumors with the greatest increase in mesenchymal marker expression had rapid clinical progression, but no difference in overall survival after second surgery. Comparison of protein and gene expression data from the same samples revealed a poor correlation. A subset of tumors (15%) showed loss of neurofibromin protein in both initial and recurrent tumors. These data support the notion that GBM progression is associated with a shift toward a mesenchymal phenotype in a subset of tumors and this may portend a more aggressive behavior.

Visual Counting and Automated Image-analytic Assessment of Ki-67 and their Prognostic Value in Synovial Sarcoma

2022 ◽  
Vol 2 (1) ◽  
pp. 7-14
Author(s):  
RIIKKA E. LAURILA ◽  
TOM O. BÖHLING ◽  
CARL P. BLOMQVIST ◽  
CHRISTINA KARLSSON ◽  
ERKKI J. TUKIAINEN ◽  
...  
Keyword(s):  
Overall Survival ◽  
Synovial Sarcoma ◽  
Cox Regression ◽  
Visual Assessment ◽  
Tissue Microarrays ◽  
Assessment Method ◽  
Ki 67 ◽  
Manual Counting ◽  
Analytic Scoring ◽  
Good Agreement

Background: Ki-67 is a widely used proliferation marker reflecting prognosis in various tumors. However, visual assessment and scoring of Ki-67 suffers from marked inter-observer and intra-observer variability. We aimed to assess the concordance of manual counting and automated image-analytic scoring methods for Ki-67 in synovial sarcoma. Patients and Methods: Tissue microarrays from 34 patients with synovial sarcoma were immunostained for Ki-67 and scored both visually and with 3DHistech QuantCenter. Results: The automated assessment of Ki-67 expression was in good agreement with the visually counted Ki-67 (rPearson=0.96, p<0.001). In a Cox regression model automated [hazard ratio (HR)=1.047, p=0.024], but not visual (HR=1.063, p=0.053) assessment method associated high Ki-67 scores with worse overall survival. Conclusion: The automated Ki-67 assessment method appears to be comparable to the visual method in synovial sarcoma and had a significant association to overall survival.

scholarly journals GATA3 as an Adjunct Prognostic Factor in Breast Cancer Patients with Less Aggressive Disease: A Study with a Review of the Literature

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 604
Author(s):  
Patrizia Querzoli ◽  
Massimo Pedriali ◽  
Rosa Rinaldi ◽  
Paola Secchiero ◽  
Paolo Giorgi Rossi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Value ◽  
Tissue Microarrays ◽  
Routine Practice ◽  
Lower Grade ◽  
Breast Cancer Patients ◽  
Wild Type ◽  
Ki 67 ◽  
Luminal B

Background: GATA binding protein 3 (GATA3) expression is positively correlated with estrogen receptor (ER) expression, but its prognostic value as an independent factor remains unclear. Thus, we undertook the current study to evaluate the expression of GATA3 and its prognostic value in a large series of breast carcinomas (BCs) with long-term follow-up. Methods: A total of 702 consecutive primary invasive BCs resected between 1989 and 1993 in our institution were arranged in tissue microarrays, immunostained for ER, progesterone receptor (PR), ki-67, HER2, p53, and GATA3, and scored. Clinico-pathological data were retrospectively collected. Results: GATA3 was evaluable in 608 (87%) of the 702 cases; it was positive in 413 (68%) cases and negative in 195 (32%) cases. GATA3 positivity was significantly associated with lower grade (p < 0.0001), size (p = 0.0463), stage (p = 0.0049), ER+ (p < 0.0001), PR+ (p < 0.0001), HER2− (p = 0.0175), and p53 wild-type pattern (p < 0.0001). The median follow-up was 183 months, GATA3 positivity was associated with better overall survival (HR 0.70, p = 0.001), and its prognostic value was retained in a multivariate analysis. The association with better overall survival was stronger in patients with grade 1–2, pT1–2, pN0, stage I–II, ER+, PR+, ki-67 < 20%, HER2−, a wild-type p53 immunohistochemical pattern, and in luminal B BC. Conclusions: Our findings indicate that GATA3 is a positive prognostic marker in BC patients, especially in patients with biologically less aggressive BC. Incorporating GATA3 immunohistochemistry into routine practice could help further stratify BC patients for their risk.

scholarly journals Gene expression and immunohistochemical analyses identify SOX2 as major risk factor for overall survival and relapse in Ewing sarcoma patients

EBioMedicine ◽  
2019 ◽  
Vol 47 ◽  
pp. 156-162 ◽  
Author(s):  
Giuseppina Sannino ◽  
Aruna Marchetto ◽  
Andreas Ranft ◽  
Susanne Jabar ◽  
Constanze Zacherl ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Risk Factor ◽  
Ewing Sarcoma ◽  
Major Risk Factor ◽  
Immunohistochemical Analyses

scholarly journals Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Francesco Schettini ◽  
Nuria Chic ◽  
Fara Brasó-Maristany ◽  
Laia Paré ◽  
Tomás Pascual ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Overall Survival ◽  
High Activity ◽  
Triple Negative ◽  
Her2 Expression ◽  
Drug Conjugates ◽  
Molecular Features ◽  
Biological Heterogeneity ◽  
Antibody Drug

AbstractNovel antibody-drug conjugates against HER2 are showing high activity in HER2-negative breast cancer (BC) with low HER2 expression (i.e., 1+ or 2+ and lack of ERBB2 amplification). However, the clinical and molecular features of HER2-low BC are yet to be elucidated. Here, we collected retrospective clinicopathological and PAM50 data from 3,689 patients with HER2-negative disease and made the following observations. First, the proportion of HER2-low was higher in HR-positive disease (65.4%) than triple-negative BC (TNBC, 36.6%). Second, within HR-positive disease, ERBB2 and luminal-related genes were more expressed in HER2-low than HER2 0. In contrast, no gene was found differentially expressed in TNBC according to HER2 expression. Third, within HER2-low, ERBB2 levels were higher in HR-positive disease than TNBC. Fourth, HER2-low was not associated with overall survival in HR-positive disease and TNBC. Finally, the reproducibility of HER2-low among pathologists was suboptimal. This study emphasizes the large biological heterogeneity of HER2-low BC, and the need to implement reproducible and sensitive assays to measure low HER2 expression.

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