High Ep-CAM Expression is Associated with Poor Prognosis in Node-positive Breast Cancer

Spizzo, Gilbert; Gastl, Guenther; Obrist, Peter; Went, Philip; Dirnhofer, Stephan; Bischoff, Susanne; Mirlacher, Martina; Sauter, Guido; Simon, Ronald; Stopatschinskaya, Shanna; Haas, Philip; Bart, Rahel; Köchli, Ossi R.; Spichtin, Hanspeter; Maurer, Robert; Metzger, U; Castelberg, Brida von; Zuber, Markus; Mross, Friedrich; Dietrich, H.

doi:10.1023/b:brea.0000036787.59816.01

Cited by 210 publications

(177 citation statements)

References 17 publications

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“…Normal-like breast cancer accounted for 7.8% of all breast cancers in 344 breast cancer samples [9] thus forming a substantial breast cancer subgroup. In accordance with our preclinical findings [10], Spizzo et al, showed that 10.3% of 1715 invasive breast cancer patient samples lacked EpCAM expression [11].…”

Section: Introductionsupporting

confidence: 91%

Detection of circulating tumor cells in breast cancer may improve through enrichment with anti-CD146

Mostert

Kraan

Vries

et al. 2010

Breast Cancer Res Treat

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PurposeMost assays to detect circulating tumor cells (CTCs) rely on EpCAM expression on tumor cells.Recently, our group reported that in contrast to other molecular breast cancer subtypes, "normallike" cell lines lack EpCAM expression and are thus missed when CTCs are captured with EpCAM-based technology [1]. Here, the use of CD146 is introduced to detect EpCAM-negative CTCs, thereby improving CTC detection. Methods CD146and EpCAM expression were assessed in our panel of 41 breast cancer cell lines. Cells from 14 cell lines, 9 of which normal-like, were spiked into healthy donor blood. Using CellSearch™ technology, 7.5 mL whole blood was enriched for CTCs by adding ferrofluids loaded with antibodies against EpCAM and/or CD146 followed by staining for Cytokeratin and DAPI. Hematopoietic cells and circulating endothelial cells (CECs) were counterstained with CD45 and CD34, respectively. A similar approach was applied for blood samples of 20 advanced breast cancer patients. ResultsEight of 9 normal-like breast cancer cell lines lacked EpCAM expression but did express CD146.Five of these 8 could be adequately recovered by anti-CD146 ferrofluids. Of 20 advanced breast cancer patients whose CTCs were enumerated with anti-EpCAM and anti-CD146 ferrofluids, 9 had CD146+ CTCs. ConclusionsCells from breast cancer cell lines that lack EpCAM expression frequently express CD146 and can be recovered by anti-CD146 ferrofluids. CD146+ CTCs are present in the peripheral blood of breast cancer patients with advanced disease. Combined use of anti-CD146 and anti-EpCAM is likely to improve CTC detection in breast cancer patients.3

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Section: Introductionsupporting

confidence: 91%

Detection of circulating tumor cells in breast cancer may improve through enrichment with anti-CD146

Mostert

Kraan

Vries

et al. 2010

Breast Cancer Res Treat

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“…12 FABP5 is up-regulated by EpCAM, 37 a tumor-associated epithelial cell adhesion molecule with a negative prognostic effect in breast cancer. 38,39 FABP5 is a major target of the proto-oncogene c-Myc, 40 which is also rapidly up-regulated by de novo expression of EpCAM, 41 and implicated in breast tumor formation and progression. 42 These results suggest an EpCAM-c-Myc-FABP5 link in human breast cancers.…”

Section: Discussionmentioning

confidence: 99%

Association of FABP5 Expression With Poor Survival in Triple-Negative Breast Cancer

Liu

Graham

Glubrecht

et al. 2011

The American Journal of Pathology

138

124

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Recent studies using animal models suggest that expression of FABP5 drives the stimulation of cell growth observed in estrogen receptor (ER)-negative breast cancer cells on exposure to retinoic acid (RA). The purpose of this study was to investigate the clinicopathological significance of FABP5 in breast cancer and to evaluate FABP5 as a prognostic marker and a possible novel therapeutic target in breast cancer. Gene expression microarray analysis revealed a significant correlation between elevated FABP5 RNA levels and ER/ progesterone receptor (PR)-negative status, high tumor grade, and poor prognosis. Tissue microarray analysis demonstrated similar correlations with cytoplasmic FABP5 protein. Based on multivariate proportional regression analysis, cytoplasmic FABP5 is a significant and independent prognostic marker of overall survival and recurrence-free survival in breast cancer. The effects of FABP5 on tumor growth appear to be mediated primarily through cytoplasmic FABP, because no correlation was found between nuclear FABP5 and ER/PRnegative status, recurrence, and survival. FABP5 knockdown in breast cancer cell lines demonstrates a correlation between FABP5 levels and growth response to RA. We propose a model whereby growth-promoting FABP5 competes with growth-inhibiting CRABP2 for RA, with retention of RA in the cytoplasm by FABP5 preventing the inhibition of tumor growth. (Am J Pathol

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“…With lung, colon, prostate and gastric cancers, we have selected four of the most frequent cancers in the industrialised world. Epithelial cell adhesion molecule expression in breast cancer has been previously published for more than 1700 patient samples (Gastl et al, 2000;Spizzo et al, 2002;Spizzo et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…As Ep-CAM is involved in adhesion, differentiation and cell proliferation, an influence of Ep-CAM expression on survival of cancer patients can be expected. In breast and gall bladder cancer, patients with high Ep-CAMexpressing primary tumours indeed showed a decreased survival (Gastl et al, 2000;Spizzo et al, 2002;Spizzo et al, 2004;Varga et al, 2004). In clear cell renal cell carcinoma, Ep-CAM expression is infrequent, but patients with Ep-CAM overexpressing tumours show a trend to better survival (Kim et al, 2004;Seligson et al, 2004;Went et al, 2005).…”

mentioning

confidence: 99%

Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers

et al. 2006

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Epithelial cell adhesion molecule (Ep-CAM; CD326) is used as a target by many immunotherapeutic approaches, but little data are available about Ep-CAM expression in major human malignancies with respect to level, frequency, tumour stage, grade, histologic tumour type and impact on survival. We analysed by immunohistochemical staining tissue microarrays with 4046 primary human carcinoma samples from colon, stomach, prostate and lung cancers for both frequency and intensity of Ep-CAM expression under highly standardised conditions. A total of 3360 samples were analysable. High-level Ep-CAM expression was observed in 97.7% (n ¼ 1186) of colon, 90.7% of gastric (n ¼ 473), and 87.2% of prostate cancers (n ¼ 414), and in 63.9% of lung cancers (n ¼ 1287). No detectable Ep-CAM staining was found with only 0.4% of colon, 2.5% of gastric, 1.9% of prostate cancers, and 13.5% of lung cancers. The only significant correlation of Ep-CAM expression with tumour grading was observed in colon cancer where high-level Ep-CAM expression on grade 3 tumours was down to 92.1% (Po0.0001). Adenosquamous and squamous carcinomas of the lung had a lower percentage of high-level Ep-CAM expression compared to adenocarcinomas with 35.4 and 53.6%, respectively, and with 45.5 and 17.3% of tumours being Ep-CAM negative. With the exception of moderately differentiated colon carcinoma, where patients not expressing Ep-CAM on their tumours showed an inferior survival (P ¼ 0.0014), correlation of Ep-CAM expression with survival did not reach statistical significance for any of the other cancer indications and subgroups. In conclusion, the data strongly support the notion that Ep-CAM is a prime target for immunotherapies in major human malignancies. This is because the most common human cancers show (i) a low frequency of Ep-CAM-negative tumours, (ii) a high frequency of Ep-CAM expression on cells of a given tumour, and (iii) for most cancers, an insignificant influence of tumour staging, grading and histology on Ep-CAM expression.

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High Ep-CAM Expression is Associated with Poor Prognosis in Node-positive Breast Cancer

Cited by 210 publications

References 17 publications

Detection of circulating tumor cells in breast cancer may improve through enrichment with anti-CD146

Detection of circulating tumor cells in breast cancer may improve through enrichment with anti-CD146

Association of FABP5 Expression With Poor Survival in Triple-Negative Breast Cancer

Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers

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