scholarly journals The Prognostic Impact of Protein Expression of E-Cadherin-Catenin Complexes Differs between Rectal and Colon Carcinoma

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Rolf Aamodt ◽  
Johan Bondi ◽  
Solveig Norheim Andersen ◽  
Arne Bakka ◽  
Geir Bukholm ◽  
...  
Keyword(s):  
Protein Expression ◽  
Clinical Information ◽  
Distant Metastases ◽  
Prognostic Impact ◽  
Inverse Association ◽  
Expression Data ◽  
P120 Catenin ◽  
Primary Tumors ◽  
Membranous Protein ◽  
E Cadherin

The E-cadherin-catenin complex provides cell-cell adhesion. In order for a carcinoma to metastasize, cancer cells must let go of their hold of neighboring cells in the primary tumor. The presence of components of the E-cadherin-catenin complex in 246 rectal adenocarcinomas was examined by immunohistochemistry and compared to their presence in 219 colon carcinomas. The expression data were correlated to clinical information from the patients' records. There were statistically significant differences in protein expression between the rectal and the colon carcinomas regarding membranous -catenin, -catenin, p120-catenin, and E-cadherin, as well as nuclear -catenin. In the rectal carcinomas, there was a significant inverse association between the expression of p120-catenin in cell membranes of the primary tumors and the occurrence of local recurrence, while membranous protein expression of -catenin was inversely related to distant metastases.

Deleted in Colon Cancer Protein Expression in Colorectal Cancer Metastases: A Major Predictor of Survival in Patients With Unresectable Metastatic Disease Receiving Palliative Fluorouracil-Based Chemotherapy

2004 ◽  
Vol 22 (18) ◽  
pp. 3758-3765 ◽  
Author(s):  
Carlo Aschele ◽  
Domizia Debernardis ◽  
Sara Lonardi ◽  
Roberto Bandelloni ◽  
Stefania Casazza ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Protein Expression ◽  
Regional Lymph Node ◽  
Survival Rates ◽  
Distant Metastases ◽  
Patient Characteristics ◽  
Rank Test ◽  
Primary Tumors ◽  
Major Predictor

Purpose To determine whether deleted in colon cancer (DCC) protein expression in colorectal cancer (CRC) metastases could predict outcome to palliative fluorouracil (FU)-based chemotherapy and to assess whether it is similar to that observed in the corresponding primary tumors. Patients and Methods DCC protein expression was assessed immunohistochemically on archival specimens of CRC metastases from 42 patients homogeneously treated by methotrexate-modulated bolus FU alternated to 6-S-leucovorin–modulated infused FU and was retrospectively correlated with patient characteristics and clinical outcome. In a subset analysis, DCC immunoreactivity was compared between metastatic CRC and the corresponding primary tumors and regional lymph node metastases. Results Positive immunoreactivity for DCC was found in 45% of patients. Eighteen (78%) of 23 patients for whom multiple samples were available displayed a similar pattern of expression in distant metastases and primary tumors. The median survival time was 14.3 months in patients without DCC expression and 21.4 months in patients with DCC-positive tumors (log-rank test, P = .04); the 2-year survival rates were 8.5% and 42.5%, respectively. Response rates to chemotherapy were not significantly different between the two groups. By multivariate analysis, DCC protein expression maintained its prognostic value and showed to be the single best predictor of survival, with a relative risk of 2.16. Conclusion Our results indicate that expression of the DCC protein in CRC metastases is similar to that observed in the corresponding primary tumors and represents a dominant predictor of survival in patients with unresectable, advanced CRC who are undergoing palliative FU-based chemotherapy.

ErbB3 protein expression in serous ovarian carcinomas of elderly women

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16026-16026
Author(s):  
M. S. Hirsch ◽  
J. Liu ◽  
R. Drapkin ◽  
H. Lee ◽  
U. A. Matulonis
Keyword(s):  
Overall Survival ◽  
Protein Expression ◽  
Ovarian Carcinoma ◽  
Elderly Women ◽  
Growth Factor Receptor ◽  
Clinical Information ◽  
Ovarian Carcinomas ◽  
Brca Mutations ◽  
Data Set ◽  
Primary Tumors

16026 Background: Ovarian carcinoma is the leading cause of death due to gynecologic malignancies, and older age at the time of diagnosis has been suggested to correlate with poorer outcome. Recent studies suggest that expression of ErbB3, a member of the epidermal growth factor receptor family, is associated with decreased survival. The goal of this study was to examine ErbB3 protein expression with a tissue microarray (TMA) comprised of advanced papillary serous (PS) ovarian carcinomas, and to correlate results with clinical information to evaluate for expression differences in younger and older women. Methods: A high density TMA (with 4 cores per primary tumor) was constructed by retrospective review of PS ovarian carcinoma cases seen between 1999 and 2005. Patients were divided into 2 cohorts based on age (=65 and =55 at diagnosis). Only cases of stage III or IV disease were included, and patients with BRCA mutations were excluded. Clinical data were obtained by chart and database review. TMA sections were immunostained for ErbB3, and expression was correlated with age, stage, and overall survival. Results: 136 primary tumors were available: 72 in the =65 group, 64 in the =55 group. Tumors from the =65 cohort were significantly less likely to express ErbB3 (16.7%) when compared to the ≤55 cohort (51.6%) (p<0.0001). Patients whose tumors expressed ErbB3 had decreased median survival (33.6 months) compared to ErbB3 negative cases (47.3 months), but these results were not statistically significant (p=0.10). ErbB3 expression correlated in a borderline significant manner with stage (dichotomized as IIIa/IIIb vs. IIIc/IV) at the time of diagnosis (stage IIIa/b 11.8%+ vs. stage IIIc/IV 36.1%+; p=0.055). Multivariate analysis with respect to age, stage, and ErbB3 status did not reveal ErbB3 to be a statistically significant predictor of poor outcome in this data set. Conclusions: These results demonstrate that PS ovarian carcinomas in patients aged =65 at the time of diagnosis are significantly less likely to express ErbB3 than those ≤55. Correlation between ErbB3 expression and more advanced stage at the time of diagnosis bordered on significance. There was a non-significant trend towards decreased overall survival in both univariate and multivariate analyses in patients whose tumors exhibited ErbB3 expression. No significant financial relationships to disclose.

Downregulation of RIZ1 protein expression in left-sided versus right-sided primary colorectal carcinomas and their distant metastases and the association with NF-B activation

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15112-e15112
Author(s):  
E. Torlakovic ◽  
E. C. Marginean ◽  
G. Torlakovic ◽  
R. Geyer ◽  
H. Neufeld ◽  
...  
Keyword(s):  
Protein Expression ◽  
Colorectal Adenocarcinoma ◽  
Nuclear Translocation ◽  
Human Cancer ◽  
Distant Metastases ◽  
Normal Mucosa ◽  
Metastatic Carcinoma ◽  
Chi Square ◽  
Primary Tumors ◽  
Molecular Events

e15112 Background: Activation of NF- B leads to enhanced proliferation and the expression of anti-apoptotic proteins, which are cancer phenotypes. RIZ1 inactivation through various molecular events was linked to increased proliferation, migration induction and apoptosis inhibition in human cancer. RIZ1 frameshift mutations were recently reported to be confined to MSI-H colorectal tumors and proximal tumor origin, while its hypermethylation was not limited to MSI-H tumors. However, RIZ1 protein expression has not been evaluated in colorectal carcinoma. Methods: TMAs included 28 left-sided and 12 right-sided primary colorectal adenocarcinomas, their matched normal mucosa and their respective distant metastases. Left-sided tumors were compared to right-sided tumors for expression of RIZ1 protein and NF- B activation. RIZ1 immunostaining was scored semiquantitatively (0–3+). NF- B activation was determined by IHC detecting nuclear translocation of its p65 subunit in more than 30% tumor nuclei. Discrepant results were defined as score difference of 2. Results: RIZ1 was less expressed in tumors than in benign mucosa (p<0.0001, r=- 0.377, Chi-Square). The difference between primary vs. metastatic carcinoma was not significant. Low RIZ1 was associated with NF- B activation (p<0.0001, Linear-by-Linear). Left-sided primary tumors showed less RIZ1 protein expression than right-sided (p=0.03, Chi-Square). NF- B activation was more frequent in left-sided primary tumors and their respective metastases (35% in right vs. 67% in left; p=0.002, Chi-Square Test). RIZ1 expression and NF- B activation were almost identical in primary and their respective metastatic tumors with only 3 discrepant results for NF- B status and 2 discrepant results in RIZ1 expression. Conclusions: While RIZ1 downregulation in colorectal adenocarcinoma due to RIZ1 mutations appears to be associated with MSI-H and proximal origin, its protein expression appears to be downregulated more often in distal tumors. NF- B activation is strongly associated with lower RIZ1 protein expression in colorectal adenocarcinoma. No significant financial relationships to disclose.

scholarly journals A Requirement for p120-catenin in the metastasis of invasive ductal breast cancer

2020 ◽  
pp. jcs.250639
Author(s):  
Sarah J. Kurley ◽  
Verena Tischler ◽  
Brian Bierie ◽  
Sergey V. Novitskiy ◽  
Aurelia Noske ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Primary Tumor ◽  
Distant Metastases ◽  
Positive Role ◽  
P120 Catenin ◽  
Primary Tumors ◽  
Invasive Ductal Breast Cancer ◽  
Metastatic Colonization ◽  
Metastatic Sites

We have examined the effects of targeted p120 KO in a PyMT mouse model of invasive ductal (mammary) cancer (IDC). Mosaic p120 ablation had little effect on primary tumor growth but caused significant pro-metastatic alterations in the tumor microenvironment leading ultimately to a marked increase in the number and size of pulmonary metastases. Surprisingly, although early effects of p120-ablation included decreased cell-cell adhesion and increased invasiveness, cells lacking p120 were almost entirely unable to colonized distant metastatic sites in vivo. The relevance of this observation to human IDC was established by analysis of a large clinical dataset of 1126 IDCs. As reported by others, p120 downregulation in primary IDC predicted worse overall survival. However, as in the mice, distant metastases were almost invariably p120 positive, even in matched cases where the primary tumors were p120 negative. Collectively, our results demonstrate a strong positive role for p120 (and presumably E-cadherin) during metastatic colonization of distant sites. On the other hand, downregulation of p120 in the primary tumor enhanced metastatic dissemination indirectly via pro-metastatic conditioning of the tumor microenvironment.

scholarly journals Expression of the Chemokine Receptor CCR7 in the Normal Adrenal Gland and Adrenal Tumors and Its Correlation with Clinical Outcome in Adrenocortical Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5693
Author(s):  
Carmina Teresa Fuss ◽  
Katharina Other ◽  
Britta Heinze ◽  
Laura-Sophie Landwehr ◽  
Armin Wiegering ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Protein Expression ◽  
Chemokine Receptor ◽  
Adrenocortical Carcinoma ◽  
Distant Metastases ◽  
Adrenal Tumors ◽  
Mrna Levels ◽  
Primary Tumors ◽  
Adrenocortical Tumors ◽  
Adrenocortical Adenomas

Background: The chemokine receptor CCR7 is crucial for an intact immune function, but its expression is also associated with clinical outcome in several malignancies. No data exist on the expression of CCR7 in adrenocortical tumors. Methods: CCR7 expression was investigated by qRT-PCR and immunohistochemistry in 4 normal adrenal glands, 59 adrenocortical adenomas, and 181 adrenocortical carcinoma (ACC) samples. Results: CCR7 is highly expressed in the outer adrenocortical zones and medulla. Aldosterone-producing adenomas showed lower CCR7 protein levels (H-score 1.3 ± 1.0) compared to non-functioning (2.4 ± 0.5) and cortisol-producing adenomas (2.3 ± 0.6), whereas protein expression was variable in ACC (1.8 ± 0.8). In ACC, CCR7 protein expression was significantly higher in lymph node metastases (2.5 ± 0.5) compared to primary tumors (1.8±0.8) or distant metastases (2.0 ± 0.4; p < 0.01). mRNA levels of CCR7 were not significantly different between ACCs, normal adrenals, and adrenocortical adenomas. In contrast to other tumor entities, neither CCR7 protein nor mRNA expression significantly impacted patients’ survival. Conclusion: We show that CCR7 is expressed on mRNA and protein level across normal adrenals, benign adrenocortical tumors, as well as ACCs. Given that CCR7 did not influence survival in ACC, it is probably not involved in tumor progression, but it could play a role in adrenocortical homeostasis.

scholarly journals Non-Coding RNAs as Biomarkers of Tumor Progression and Metastatic Spread in Epithelial Ovarian Cancer

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1839
Author(s):  
Karolina Seborova ◽  
Radka Vaclavikova ◽  
Lukas Rob ◽  
Pavel Soucek ◽  
Pavel Vodicka
Keyword(s):  
Ovarian Cancer ◽  
Tumor Progression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Distant Metastases ◽  
Regulatory Elements ◽  
Metastatic Spread ◽  
Response To Treatment ◽  
Primary Tumors ◽  
Non Coding Rnas

Ovarian cancer is one of the most common causes of death among gynecological malignancies. Molecular changes occurring in the primary tumor lead to metastatic spread into the peritoneum and the formation of distant metastases. Identification of these changes helps to reveal the nature of metastases development and decipher early biomarkers of prognosis and disease progression. Comparing differences in gene expression profiles between primary tumors and metastases, together with disclosing their epigenetic regulation, provides interesting associations with progression and metastasizing. Regulatory elements from the non-coding RNA families such as microRNAs and long non-coding RNAs seem to participate in these processes and represent potential molecular biomarkers of patient prognosis. Progress in therapy individualization and its proper targeting also rely upon a better understanding of interactions among the above-listed factors. This review aims to summarize currently available findings of microRNAs and long non-coding RNAs linked with tumor progression and metastatic process in ovarian cancer. These biomolecules provide promising tools for monitoring the patient’s response to treatment, and further they serve as potential therapeutic targets of this deadly disease.

scholarly journals Improved risk estimation of locoregional recurrence, secondary contralateral tumors and distant metastases in early breast cancer: the INFLUENCE 2.0 model

2021 ◽  
Author(s):  
Vinzenz Völkel ◽  
Tom A. Hueting ◽  
Teresa Draeger ◽  
Marissa C. van Maaren ◽  
Linda de Munck ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Locoregional Recurrence ◽  
Clinical Decision Making ◽  
Metastatic Breast ◽  
Distant Metastases ◽  
Time Dependent ◽  
Individual Risk ◽  
Primary Tumors ◽  
Statistical Approaches

Abstract Purpose To extend the functionality of the existing INFLUENCE nomogram for locoregional recurrence (LRR) of breast cancer toward the prediction of secondary primary tumors (SP) and distant metastases (DM) using updated follow-up data and the best suitable statistical approaches. Methods Data on women diagnosed with non-metastatic invasive breast cancer were derived from the Netherlands Cancer Registry (n = 13,494). To provide flexible time-dependent individual risk predictions for LRR, SP, and DM, three statistical approaches were assessed; a Cox proportional hazard approach (COX), a parametric spline approach (PAR), and a random survival forest (RSF). These approaches were evaluated on their discrimination using the Area Under the Curve (AUC) statistic and on calibration using the Integrated Calibration Index (ICI). To correct for optimism, the performance measures were assessed by drawing 200 bootstrap samples. Results Age, tumor grade, pT, pN, multifocality, type of surgery, hormonal receptor status, HER2-status, and adjuvant therapy were included as predictors. While all three approaches showed adequate calibration, the RSF approach offers the best optimism-corrected 5-year AUC for LRR (0.75, 95%CI: 0.74–0.76) and SP (0.67, 95%CI: 0.65–0.68). For the prediction of DM, all three approaches showed equivalent discrimination (5-year AUC: 0.77–0.78), while COX seems to have an advantage concerning calibration (ICI < 0.01). Finally, an online calculator of INFLUENCE 2.0 was created. Conclusions INFLUENCE 2.0 is a flexible model to predict time-dependent individual risks of LRR, SP and DM at a 5-year scale; it can support clinical decision-making regarding personalized follow-up strategies for curatively treated non-metastatic breast cancer patients.

scholarly journals The Prognostic Impact of HER2 Genetic and Protein Expression in Pancreatic Carcinoma—HER2 Protein and Gene in Pancreatic Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 653
Author(s):  
Song-Hee Han ◽  
Ki Hyun Ryu ◽  
Ah-Young Kwon
Keyword(s):  
Protein Expression ◽  
Genetic Heterogeneity ◽  
Growth Factor Receptor ◽  
Ductal Adenocarcinoma ◽  
Prognostic Impact ◽  
Her2 Expression ◽  
Her2 Protein ◽  
Epidermal Growth ◽  
Her2 Heterogeneity

Pancreatic ductal adenocarcinoma (PDAC) is a lethal and clinically heterogeneous disease with a limited benefit from human epidermal growth factor receptor 2 (HER2)-targeted therapy. Recently, some studies have addressed the antitumoral effect of novel anti-HER2 drugs in HER2 low-expressing tumors. However, there have been few studies on the significance of low HER2 expression and genetic heterogeneity in PDAC. Using immunohistochemistry and dual-color silver-enhanced in situ hybridization based on the Trastuzumab for a gastric cancer scoring scheme, we evaluated HER2 protein expression, gene amplification, and genetic heterogeneity in three groups (HER2-neg, HER2-low, HER2-pos) of 55 patients. Among the 55 cases, 41.8% (23/55) showed HER2 expression of any intensity. HER2 amplification independent of HER2 expression was 25.5% (14/55). Patients in both these groups had a shorter overall survival than did patients in the HER2-neg group. HER2 genetic heterogeneity was identified in 37 (70.9%) of the 55 cases, mainly in HER2-neg and HER2-low groups. HER2 genetic heterogeneity significantly correlated with worse survival in the HER2-low and HER2-neg groups of PDAC. These findings support the hypothesis that low-level HER2 expression and heterogeneity have significant clinical implications in PDAC. HER2 heterogeneity might indicate the best strategies of combination therapies to prevent the development of subdominant clones with resistance potential.

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