Ep-CAM overexpression in breast cancer as a predictor of survival

Gastl, Günther; Spizzo, Gilbert; Obrist, Peter; Dünser, Martina; Mikuz, Gregor

doi:10.1016/s0140-6736(00)03312-2

Cited by 229 publications

(207 citation statements)

References 5 publications

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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).…”

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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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Section: Discussionmentioning

confidence: 99%

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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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“…35 By contrast, Ep-CAM expression on certain tumors such as prostate and gastric carcinoma reaches 100% as examined by immunohistochemistry. 16,36 Moreover, Ep-CAM was found to be significantly upregulated with disease progression in several cancers including breast cancer, [17][18][19]37 suggesting that Ep-CAM expression on tumor cells confers a growth, invasion and/or survival benefit. A recent study showed that Ep-CAM can interact with the negative regulatory receptor LAIR-1 present on most immune cells.…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo activity of MT201, a fully human monoclonal antibody for pancarcinoma treatment

Naundorf

Preithner

Mayer

et al. 2002

Intl Journal of Cancer

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In our study, a novel, fully human, recombinant monoclonal antibody of the IgG1 isotype, called MT201, was characterized for its binding properties, complement-dependent (CDC) and antibody-dependent cellular cytotoxicity (ADCC), as well as for its in vivo antitumor activity in a nude mouse model. MT201 was found to bind its target, the epithelial cell adhesion molecule (Ep-CAM; also called 17-1A antigen, KSA, EGP-2, GA733-2), with low affinity in a range similar to that of the clinically validated, murine monoclonal IgG2a antibody edrecolomab (Panorexா). MT201 exhibited Ep-CAM-specific CDC with a potency similar to that of edrecolomab. However, the efficacy of ADCC of MT201, as mediated by human immune effector cells, was by 2 orders of magnitude higher than that of edrecolomab. Addition of human serum reduced the ADCC of MT201 while it essentially abolished ADCC of edrecolomab within the concentration range tested. In a nude mouse xenograft model, growth of tumors derived from the human colon carcinoma line HT-29 was significantly and comparably suppressed by MT201 and edrecolomab. The fully human nature and the improved ADCC of MT201 with human effector cells will make MT201 a promising candidate for the clinical development of a novel pan-carcinoma antibody that is superior to edrecolomab.

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“…Therefore, TROP2 'overexpression' was arbitrarily defined as a total score Z4 as described previously. 13 To assess the validity of the tissue microarray technique, we also analyzed full tissue sections using the same staining methods in a subset of 30 cases and matched them with the corresponding core sample. In 93% of the samples, analysis of a single punched core matched the staining pattern of a whole section.…”

Section: Evaluation Of Slidesmentioning

confidence: 99%

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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Ep-CAM overexpression in breast cancer as a predictor of survival

Cited by 229 publications

References 5 publications

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

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

In vitro and in vivo activity of MT201, a fully human monoclonal antibody for pancarcinoma treatment

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

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