scholarly journals Evaluation of soluble carbonic anhydrase IX as predictive marker for efficacy of bevacizumab: A biomarker analysis from the geparquinto phase III neoadjuvant breast cancer trial

2019 ◽  
Vol 145 (3) ◽  
pp. 857-868 ◽  
Author(s):  
Melanie Janning ◽  
Volkmar Müller ◽  
Eik Vettorazzi ◽  
Miguel Cubas-Cordova ◽  
Victoria Gensch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Carbonic Anhydrase ◽  
Predictive Marker ◽  
Carbonic Anhydrase Ix ◽  
Phase Iii ◽  
Cancer Trial ◽  
Biomarker Analysis ◽  
Soluble Carbonic Anhydrase

Serum carbonic anhydrase IX as predictive marker for efficacy of bevacizumab: A biomarker analysis from the GeparQuinto phase III neoadjuvant breast cancer trial.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 11505-11505 ◽  
Author(s):  
Janning Melanie ◽  
Volkmar Müller ◽  
Eik Vettorazzi ◽  
Miguel Cubas-Cordova ◽  
Christine Eulenburg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Carbonic Anhydrase ◽  
Predictive Marker ◽  
Carbonic Anhydrase Ix ◽  
Phase Iii ◽  
Cancer Trial ◽  
Biomarker Analysis

scholarly journals Granulocyte Colony Stimulating Factor Expression in Breast Cancer and Its Association with Carbonic Anhydrase IX and Immune Checkpoints

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1022
Author(s):  
Shawn C. Chafe ◽  
Nazia Riaz ◽  
Samantha Burugu ◽  
Dongxia Gao ◽  
Samuel C. Y. Leung ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Carbonic Anhydrase ◽  
Immune Checkpoint ◽  
Positive Association ◽  
Carcinoma Cells ◽  
Carbonic Anhydrase Ix ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Significant Positive Association ◽  
Stimulating Factor

Purpose: Granulocyte colony-stimulating factor (G-CSF) and hypoxia modulate the tumour immune microenvironment. In model systems, hypoxia-induced carbonic anhydrase IX (CAIX) has been associated with G-CSF and immune responses, including M2 polarization of macrophages. We investigated whether these associations exist in human breast cancer specimens, their relation to breast cancer subtypes, and clinical outcome. Methods: Using validated protocols and prespecified scoring methodology, G-CSF expression on carcinoma cells and CD163 expression on tumour-associated macrophages were assayed by immunohistochemistry and applied to a tissue microarray series of 2960 primary excision specimens linked to clinicopathologic, biomarker, and outcome data. Results: G-CSFhigh expression showed a significant positive association with ER negativity, HER2 positivity, presence of CD163+ M2 macrophages, and CAIX expression. In univariate analysis, G-CSFhigh phenotype was associated with improved survival in non-luminal cases, although the CAIX+ subset had a significantly adverse prognosis. A significant positive association was observed between immune checkpoint biomarkers on tumour-infiltrating lymphocytes and both G-CSF- and CAIX-expressing carcinoma cells. Immune checkpoint biomarkers correlated significantly with favourable prognosis in G-CSFhigh/non-luminal cases independent of standard clinicopathological features. Conclusions: The prognostic associations linking G-CSF to immune biomarkers and CAIX strongly support their immunomodulatory roles in the tumour microenvironment.

scholarly journals A non-catalytic function of carbonic anhydrase IX contributes to the glycolytic phenotype and pH regulation in human breast cancer cells

2019 ◽  
Vol 476 (10) ◽  
pp. 1497-1513 ◽  
Author(s):  
Mam Y. Mboge ◽  
Zhijuan Chen ◽  
Daniel Khokhar ◽  
Alyssa Wolff ◽  
Lingbao Ai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Carbonic Anhydrase ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Expression Patterns ◽  
Extracellular Ph ◽  
Carbonic Anhydrase Ix ◽  
Monocarboxylate Transporter ◽  
Proton Efflux ◽  
Ca Ix

AbstractThe most aggressive and invasive tumor cells often reside in hypoxic microenvironments and rely heavily on rapid anaerobic glycolysis for energy production. This switch from oxidative phosphorylation to glycolysis, along with up-regulation of the glucose transport system, significantly increases the release of lactic acid from cells into the tumor microenvironment. Excess lactate and proton excretion exacerbate extracellular acidification to which cancer cells, but not normal cells, adapt. We have hypothesized that carbonic anhydrases (CAs) play a role in stabilizing both intracellular and extracellular pH to favor cancer progression and metastasis. Here, we show that proton efflux (acidification) using the glycolytic rate assay is dependent on both extracellular pH (pHe) and CA IX expression. Yet, isoform-selective sulfonamide-based inhibitors of CA IX did not alter proton flux, which suggests that the catalytic activity of CA IX is not necessary for this regulation. Other investigators have suggested the CA IX co-operates with the MCT transport family to excrete protons. To test this possibility, we examined the expression patterns of selected ion transporters and show that members of this family are differentially expressed within the molecular subtypes of breast cancer. The most aggressive form of breast cancer, triple-negative breast cancer, appears to co-ordinately express the monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CA IX). This supports a possible mechanism that utilizes the intramolecular H+ shuttle system in CA IX to facilitate proton efflux through MCT4.

Prognostic Significance of a Novel Hypoxia-Regulated Marker, Carbonic Anhydrase IX, in Invasive Breast Carcinoma

2001 ◽  
Vol 19 (16) ◽  
pp. 3660-3668 ◽  
Author(s):  
Stephen K. Chia ◽  
Charles C. Wykoff ◽  
Peter H. Watson ◽  
Cheng Han ◽  
Russell D. Leek ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Breast Carcinoma ◽  
Carbonic Anhydrase ◽  
Invasive Breast Cancer ◽  
Estrogen Receptor Status ◽  
Prognostic Significance ◽  
Invasive Breast Carcinoma ◽  
Carbonic Anhydrase Ix ◽  
Ca Ix

PURPOSE: To assess the frequency of expression and the prognostic significance of a hypoxia-regulated marker, carbonic anhydrase IX (CA IX), in a cohort of patients with invasive breast cancer. PATIENTS AND METHODS: CA IX expression was evaluated by immunohistochemistry with a murine monoclonal antibody, M75, in a series of 103 women treated surgically for invasive breast cancer. The majority of patients were treated with adjuvant hormonal or chemotherapy. The frequency of CA IX expression, its association with recognized prognostic factors, and the relationship with outcome was evaluated by univariate and multivariate statistical analyses. RESULTS: CA IX expression was present in 49 (48%) of 103 cases. The level of CA IX expression was found to be significantly associated with tumor necrosis (P < .001), higher grade (P = .02), and negative estrogen receptor status (P < .001). Furthermore, CA IX expression was associated with a higher relapse rate (P = .004) and a worse overall survival (P = .001). By multivariate analysis, CA IX was also shown to be an independent predictive factor for overall survival (hazard ratio, 2.61; 95% confidence interval, 1.01 to 6.75, P = .05). CONCLUSION: CA IX expression was associated with worse relapse-free survival and overall survival in an unselected cohort of patients with invasive breast carcinoma. The potential role of CA IX as a marker of hypoxia within breast carcinomas was also indicated by a significant association with necrosis. Further work assessing its prognostic significance in breast cancer is warranted, particularly interactions with radiotherapy and chemotherapy resistance.

scholarly journals Depletion of carbonic anhydrase IX abrogates hypoxia-induced overexpression of stanniocalcin-1 in triple negative breast cancer cells

2017 ◽  
Vol 18 (8) ◽  
pp. 596-605 ◽  
Author(s):  
Elīna Zandberga ◽  
Pawel Zayakin ◽  
Artūrs Ābols ◽  
Dārta Pūpola ◽  
Pēteris Trapencieris ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Carbonic Anhydrase ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Carbonic Anhydrase Ix
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