Utility of BER‐EP4 in the diagnosis of adenocarcinoma in effusions: An immunocytochemical study of 232 cases

Diaz-Arias, Alberto A.; Loy, Timothy S.; Bickel, John T.; Chapman, Robert K.

doi:10.1002/dc.2840090509

Cited by 58 publications

(42 citation statements)

References 21 publications

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“…Another anti-FoxM1 therapeutic strategy that originated from findings in cancer cell lines was that the transcription activity of FoxM1 can be inhibited by the tumour suppressor p14ARF (p19ARF in mice), through a region mapped to residues 26-46 of the protein (43). In addition, administration of a cell-penetrating ARF [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] peptide to mice diminished FoxM1 function in vivo, causing selective apoptosis and reduced proliferation and angiogenesis in hepatocellular carcinomas (HCC) (44). Our data point to the intriguing possibility that the concomitant targeting of FoxM1 and HER2 may provide additional levels of cell death, delay or circumvent the development of resistance, whilst retaining tumour-selectivity.…”

Section: Discussionmentioning

confidence: 99%

“…Cells were then cytospun for 5 min, air dried and stored at -20˚C. This method has previously been characterised, and tumour cells isolated using this protocol commonly exhibit a high degree of purity (>95%) (33,34). As with the immunohistochemical stained samples, HER2 status of the purified epithelial cells from primary tumours were determined by fluorescent in situ hybridisation (FISH).…”

Section: Purification Of Malignant Epithelial Cells From Primary Tumomentioning

confidence: 99%

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FoxM1 is a downstream target and marker of HER2 overexpression in breast cancer

Francis

Myatt²,

Krol³

et al. 2009

Int J Oncol

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Abstract. The tyrosine kinase receptor, HER2 is a crucial prognostic marker and therapeutic target for breast cancer; however, the downstream targets and biological effectors of HER2 remain unclear. We investigated the relationship between HER2 and the transcription factor FoxM1 in breast cancer. HER2 and FoxM1 expression levels were compared in breast carcinoma cell lines, paraffin-embedded breast cancer patient samples and at the mRNA level in purified breast epithelial cells. To further examine the relationship between HER2 and FoxM1 expression, we either overexpressed or siRNA-mediated depleted endogenous HER2 in breast cancer cell lines. Additionally, a mammary epithelium-targeted HER2 (neu) transgenic mouse model was also used to assess the effect of HER2 on FoxM1 levels. Furthermore, the effect of the HER2-tyrosine kinase inhibitor lapatinib on FoxM1 in HER2 positive breast cancer cells was investigated. HER2 protein levels directly correlated with FoxM1 expression in both breast carcinoma cell lines and paraffin-embedded breast cancer patient samples. Moreover, in purified breast epithelial cells, overexpression of HER2 was associated with high levels of FoxM1 mRNA, suggesting that the upregulation of FoxM1 expression is at least partially mediated transcriptionally. Furthermore, overexpression or ablation of endogenous HER2 resulted in parallel changes in FoxM1 expression. Critically, mammary epithelium-targeted HER2 mouse tumours also resulted in increased FoxM1 expression, suggesting that HER2 directed FoxM1 expression occurs in vivo and may be a critical downstream effector of HER2-targeting therapies. Indeed, treatment of breast cancer cells with lapatinib reduced FoxM1 expression at protein, mRNA and gene promoter levels. Moreover, analysis of normal and breast cancer patient samples revealed that elevated FoxM1 expression at protein and mRNA levels correlated with breast cancer development, but not significantly with cancer progression and survival. Our results indicate that the HER2 receptor regulates the expression of the FoxM1 transcription factor, which has a role in breast cancer development.

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Section: Discussionmentioning

confidence: 99%

Section: Purification Of Malignant Epithelial Cells From Primary Tumomentioning

confidence: 99%

FoxM1 is a downstream target and marker of HER2 overexpression in breast cancer

Francis

Myatt²,

Krol³

et al. 2009

Int J Oncol

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“…Although in >90% of ovarian cancer patients EpCAM is overexpressed on tumor cells in the ascites fluid (9), the EpCAM antigen is also expressed on normal epithelial tissues (10). However, within the peritoneal cavity, EpCAM expression is tumor-specific because normal cells in the peritoneal compartment are of mesothelial origin and do not express EpCAM on their surface.…”

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confidence: 99%

Effective Relief of Malignant Ascites in Patients with Advanced Ovarian Cancer by a Trifunctional Anti-EpCAM × Anti-CD3 Antibody: A Phase I/II Study

Burges

Wimberger

Kümper

et al. 2007

Clinical Cancer Research

226

160

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Purpose: Malignant ascites in ovarian carcinoma patients is associated with poor prognosis and reduced quality of life. The trifunctional antibody catumaxomab (anti-EpCAM × anti-CD3) enhances the antitumor activity by redirecting T cells and Fcγ receptor I/III–positive accessory cells to the tumor. This multicenter phase I/II dose-escalating study investigated tolerability and efficacy of i.p. catumaxomab application in ovarian cancer patients with malignant ascites containing epithelial cell adhesion molecule (EpCAM)–positive tumor cells. Experimental Design: Twenty-three women with recurrent ascites due to pretreated refractory ovarian cancer were treated with four to five i.p. infusions of catumaxomab in doses of 5 to 200 μg within 9 to 13 days. Results: The maximum tolerated dose was defined at 10, 20, 50, 200, and 200 μg for the first through fifth doses. Side effects included transient fever (83%), nausea (61%), and vomiting (57%), mostly CTCAE (Common Terminology Criteria for Adverse Events) grade 1 or 2. A total of 39 grade 3 and 2 grade 4 treatment-related adverse events (AE), 9 of them after the highest dose level (200 μg), were observed in 16 patients. Most AEs were reversible without sequelae. Treatment with catumaxomab resulted in significant and sustained reduction of ascites flow rate. A total of 22/23 patients did not require paracentesis between the last infusion and the end of study at day 37. Tumor cell monitoring revealed a reduction of EpCAM-positive malignant cells in ascites by up to 5 log. Conclusion: I.p. immunotherapy with catumaxomab prevented the accumulation of ascites and efficiently eliminated tumor cells with an acceptable safety profile. This suggests that catumaxomab is a promising treatment option in ovarian cancer patients with malignant ascites.

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“…Moreover, the epitope recognized by this antibody is not yet characterized. 4,[8][9][10][11] Although it seems that LeuM1 (anti-CD15) may be specific, it is less sensitive than the other antibodies. 12,13 Results on CEA sensitivity and specificity are very controversial in the literature due to the use of various monoclonal or polyclonal antibodies.…”

mentioning

confidence: 99%

Diagnostic value of MUC4 immunostaining in distinguishing epithelial mesothelioma and lung adenocarcinoma

et al. 2004

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The distinction between pleural malignant mesothelioma and pleural infiltration by adenocarcinomas has complex therapeutic and medicolegal implications. Although the panel of adenocarcinoma-associated antibodies and one or two mesothelioma markers is useful in this purpose, most of these antibodies are not totally specific. We determined the diagnostic value of MUC4 immunostaining in this issue. MUC4 gene expression was also studied by in situ hybridization and RT-PCR. MUC4 is a membrane-bound mucin that has been suggested to be implicated in malignant progression in humans and rats. The MUC4 gene is expressed in various normal epithelial tissues of endodermic origin and carcinomas. In the respiratory tract, MUC4 transcripts have been detected in normal respiratory epithelium and lung carcinomas. MUC4 protein was expressed in 32 of 35 (91.4%) lung adenocarcinomas on paraffin-embedded tissue. None of the 41 malignant mesotheliomas nor the 32 cases of benign mesothelial cells expressed MUC4 at the protein and mRNA levels. We conclude that MUC4 is a very specific (100%) and sensitive (91.4%) marker of lung adenocarcinomas on paraffin-embedded tissue that could be useful in diagnostic practice in the distinction between malignant mesothelioma and adenocarcinoma.

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Utility of BER‐EP4 in the diagnosis of adenocarcinoma in effusions: An immunocytochemical study of 232 cases

Cited by 58 publications

References 21 publications

FoxM1 is a downstream target and marker of HER2 overexpression in breast cancer

FoxM1 is a downstream target and marker of HER2 overexpression in breast cancer

Effective Relief of Malignant Ascites in Patients with Advanced Ovarian Cancer by a Trifunctional Anti-EpCAM × Anti-CD3 Antibody: A Phase I/II Study

Diagnostic value of MUC4 immunostaining in distinguishing epithelial mesothelioma and lung adenocarcinoma

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