Overexpression of Epithelial Cell Adhesion Molecule Antigen in Gallbladder Carcinoma Is an Independent Marker for Poor Survival

Varga, Meri; Obrist, Peter; Schneeberger, S.; Mühlmann, Gilbert; Felgel-Farnholz, Christina; Fong, Dominic; Zitt, Matthias; Brunhuber, Thomas; Schäfer, Georg; Gastl, Guenther; Spizzo, Gilbert

doi:10.1158/1078-0432.ccr-03-0528

Cited by 131 publications

(111 citation statements)

References 21 publications

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“…Efforts for standardising the immunohistochemical staining and evaluation procedure were explained highlighting an advanced scoring system that reflected both frequency, and intensity of staining. A similar negative correlation between EpCAM expression and survival as previously observed by the group for breast and gall bladder cancer (Varga et al, 2004) was also now observed with ampullary carcinoma of the pancreas (Fong et al, 2006) and for squamous cell cancer of head and neck. N Stoecklein (Duesseldorf, Germany) reported a negative correlation between EpCAM expression and overall survival in patients with squamous cell carcinoma of the oesophagus, a very deadly disease with no established systemic treatment option.…”

Section: Epcam Expression and Survival Prognosis Of Cancer Patientssupporting

confidence: 86%

EpCAM (CD326) finding its role in cancer

Baeuerle¹,

2007

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Although epithelial cell adhesion/activating molecule (EpCAM/CD326) is one of the first tumour-associated antigens identified, it has never received the same level of attention as other target proteins for therapy of cancer. It is also striking that ever since its discovery in the late 1970s the actual contribution of EpCAM to carcinogenesis remained unexplored until very recently. With a First International Symposium on EpCAM Biology and Clinical Application this is now changing. Key topics discussed at the meeting were the frequency and level of EpCAM expression on various cancers and its prognostic potential, the role of EpCAM as an oncogenic signalling molecule for cancer cells, recent progress on EpCAM-directed immunotherapeutic approaches in clinical development and the interaction of EpCAM with other proteins, which may provide a basis for a therapeutic window and repression of its growthpromoting signalling in carcinoma. Future research on EpCAM may benefit from a unified nomenclature and more frequent exchange among those who have been working on this cancer target during the past 30 years and will do so in the future.

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Section: Epcam Expression and Survival Prognosis Of Cancer Patientssupporting

confidence: 86%

EpCAM (CD326) finding its role in cancer

Baeuerle¹,

2007

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“…The emerging functional importance of Ep-CAM for tumour cells would be more consistent with the phenotype of breast and gall bladder cancers, where Ep-CAM overexpression is an independent predictor of poor survival Varga et al, 2004). Overexpressed Ep-CAM was shown to provide a potent growth stimulus to tumour cells enabling proliferation , and led to an increased invasiveness and migration of tumour cells presumably due to Ecadherin antagonism (Litvinov et al, 1997;Osta et al, 2004).…”

Section: Discussionmentioning

confidence: 74%

“…Previous studies investigated the influence of Ep-CAM expression on survival in a number of other carcinoma. Epithelial cell adhesion molecule upregulation was an independent marker for poor survival in lymph node positive breast cancers , and gall bladder cancers (Varga et al, 2004). In contrast, improved survival was found associated with Ep-CAM upregulation in clear cell renal cell carcinoma (Kim et al, 2004;Seligson et al, 2004;Went et al, 2005), and gastric cancers (Songun et al, 2005).…”

Section: Discussionmentioning

confidence: 93%

“…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).…”

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confidence: 99%

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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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“…We recently showed that EpCAM (TROP1, GA733-2) overexpression predicts poor survival in different cancer entities. [14][15][16] Interestingly, expression of TROP2 did not correlate with EpCAM expression. 17 Anti-EpCAM antibodies can cause significant reduction in mortality and relapse rates of resected colon cancer patients following treatment with the EpCAM-specific monoclonal antibody edrecolomab.…”

Section: Discussionmentioning

confidence: 96%

TROP2: a novel prognostic marker in squamous cell carcinoma of the oral cavity

et al. 2008

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Squamous cell carcinoma is by far the most common type of cancer of the oral cavity, representing more than 90% of all oral cancers. Despite refinement of surgical techniques and adjuvant therapies, the prognosis for patients with oral squamous cell carcinoma remains poor. Identification of prognostic factors related to tumor biology might improve this assessment. Recently, the human trophoblast cell-surface antigen TROP2 was found to be highly expressed in colorectal cancer, correlating with aggressiveness and poor prognosis. Thus, the aim of this study was to investigate TROP2 expression and its prognostic impact in oral squamous cell carcinoma patients. TROP2 expression was examined by immunohistochemistry in a series of 90 patients on a tissue microarray of paraffin-embedded specimens. Survival was calculated using Kaplan-Meier estimates. Parameters found to be of prognostic significance in univariate analysis were verified in a multivariate Cox regression model. TROP2 overexpression was observed in 52 (58%) of the tumor samples. Kaplan-Meier curves showed that TROP2 overexpression was significantly associated with decreased overall survival (Po0.01). Overall survival gradually worsened with increasing TROP2 scores. By univariate analyses, no correlation with conventional clinicopathological features was found. Multivariate Cox regression analysis revealed TROP2 overexpression to be an independent factor predictive of poor disease outcome (Po0.01). These results demonstrate that TROP2 overexpression is an independent prognostic marker in patients with oral squamous cell carcinoma. TROP2 overexpression was detectable in 58% of the tumor samples, indicating it to be a potential novel therapeutic target in squamous cell carcinoma of the oral cavity.

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Overexpression of Epithelial Cell Adhesion Molecule Antigen in Gallbladder Carcinoma Is an Independent Marker for Poor Survival

Cited by 131 publications

References 21 publications

EpCAM (CD326) finding its role in cancer

EpCAM (CD326) finding its role in cancer

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

TROP2: a novel prognostic marker in squamous cell carcinoma of the oral cavity

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