Prognostic significance of Ep‐CAM AND Her‐2/neu overexpression in invasive breast cancer

Spizzo, Gilbert; Obrist, Peter; Ensinger, Christian; Theurl, Igor; Dünser, Martina; Ramoni, A; Gunsilius, Eberhard; Eibl, Günther; Mikuz, Gregor; Gastl, Günther

doi:10.1002/ijc.10270

Cited by 92 publications

(80 citation statements)

References 31 publications

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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: 94%

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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Section: Discussionmentioning

confidence: 94%

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

et al. 2008

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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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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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“…In a retrospective study of 205 lymph node-positive breast cancer patients, Gastl and co-workers (Spizzo et al, 2002) compared the prognostic impact of HER-2 and Ep-CAM overexpression on patient survival. A highly significant negative correlation was found between the expression level of Ep-CAM and disease-free and overall survival.…”

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confidence: 99%

“…Trastuzumab is believed to mediate killing of HER-2 overexpressing tumour cells via ADCC, CDC as well as interference with HER-2 signalling (Sliwkowski et al, 1999). However, as only approximately 15% of breast cancer patients highly overexpress HER-2, and thus benefit from trastuzumab treatment (Spizzo et al, 2002), the majority of breast cancer patients are still in need of IgG1 antibody-based therapies targeting other more widespread antigens.…”

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confidence: 99%

Cellular and complement-dependent cytotoxicity of Ep-CAM-specific monoclonal antibody MT201 against breast cancer cell lines

Prang¹,

Preithner²,

Brischwein³

et al. 2005

Br J Cancer

130

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MT201 is a fully human monoclonal IgG1 antibody with moderate affinity for epithelial cell adhesion molecule (Ep-CAM) being clinically developed for the treatment of carcinomas. Like many other clinically validated IgG1 monoclonal antibodies, MT201 primarily acts by antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Here, we analysed ADCC and CDC induced by MT201 and, as reference, trastuzumab against a panel of nine human breast cancer cell lines expressing distinct surface levels of Ep-CAM and human epithelial growth factor receptor type 2 antigen. Maximal cell lysis by ADCC by MT201 and trastuzumab in the presence of peripheral mononuclear cells did not significantly differ when averaged over the nine cell lines, but showed marked differences with respect to individual cell lines. The extent of cell lysis at intermediate surface target density was highly variable, suggesting a dominant influence of other susceptibility factors. Only one breast cancer cell line was eliminated via CDC, but only by MT201. Resistance to CDC appeared to correlate with high expression levels of complement resistance factors. Our present data as well as recent data on the prevalence and prognostic relevance of Ep-CAM expression in metastatic breast cancer suggest that Ep-CAM-specific monoclonal IgG1 antibodies may have a significant therapeutic potential in the treatment of breast cancer.

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Prognostic significance of Ep‐CAM AND Her‐2/neu overexpression in invasive breast cancer

Cited by 92 publications

References 31 publications

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

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

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

Cellular and complement-dependent cytotoxicity of Ep-CAM-specific monoclonal antibody MT201 against breast cancer cell lines

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