Biomedical subjects

Martina Mirlacher

Publications and source records attributed to Martina Mirlacher.

At least 19 recordsLinked to original sources

PubMed2006

HER2, TOP2A, CCND1, EGFR and C-MYC oncogene amplification in colorectal cancer.

AIM: Recent studies had suggested substantial molecular differences between tumours from different ethnic groups. In this study, the molecular differences between the incidences of colorectal carcinoma in Saudi and Swiss populations are investigated. METHOD: 518 cases of colon cancer tumours (114 from Saudi Arabia and 404 from Switzerland) were analysed in a tissue microarray format. Fluorescence in situ hybridisation (FISH) was used to estimate frequencies of copy number changes of known oncogenes, including HER2, TOPO2A, CCND1, EGFR and C-MYC. RESULTS: Using FISH, amplifications were mostly low level (gene-to-centromere ratio 2 to 4), which is in contrast with other tumour types with more frequent gene amplifications. The amplifications were particularly frequent for MYC (Saudi 9% and Swiss 14.2%) but unrelated to clinical outcome and pathological information. Remarkably, there were four tumours exhibiting classic high-level gene amplification for HER2 (Swiss 1.3%), a pattern often accompanied by response to trastuzumab (Herceptin) in breast cancer. Occasional high-level amplifications were also observed for CCND1 (Saudi 1/106, 0.9%; Swiss 2/373, 0.5%) and EGFR (Swiss 2/355; 0.6%). CONCLUSIONS: Rare high-level amplifications of therapeutic target genes were found in patients with colon cancer. Although no molecular differences were found between incidences of colon cancer cases in Swiss and Saudi populations, these observations emphasise the urgent need for clinical studies investigating the effect of targeted therapies.

Adult↗

PubMed2006

Nuclear and cytoplasmic Maspin expression in primary non-small cell lung cancer.

AIM: To investigate whether nuclear and cytoplasmic Maspin expression is associated with distinct clinicopathological parameters and TP53 expression in a representative series of primary non-small cell lung cancer (NSCLC). METHODS: Tissue microarrays (n=487) were used to immunohistochemically analyse expression of Maspin and TP53. Cytoplasmic and nuclear expression of Maspin was scored on the basis of the percentage of positive tumour cells. Univariate analysis of clinicopathological variables potentially affecting tumour-specific survival was performed. RESULTS: Immunohistochemical Maspin expression (nuclear and cytoplasmic) was informative in 72.3% (352/487) of cases. Cytoplasmic and nuclear Maspin immunoreactivity in >or=10% of tumour cells was detected in 37.8% (133/352) and 65.3% (230/352) of informative cases, respectively. Nuclear and cytoplasmic Maspin staining was observed more frequently in primary squamous cell carcinomas than in other lung cancer types. Only nuclear Maspin immunoreactivity was significantly associated with positive TP53 staining. Cytoplasmic or nuclear Maspin expression was not associated with tumour-specific survival. CONCLUSION: Maspin expression was found both in the nucleus and the cytoplasm of NSCLC, more frequently in squamous cell carcinomas. However, no association with tumour-specific survival could be demonstrated.

Biomarkers, Tumor↗

PubMed2006

Tissue microarrays for comparing molecular features with proliferation activity in breast cancer.

Tissue microarrays (TMAs) are potentially suited to find associations between molecular features and clinical outcome. Enhanced cell proliferation, as measured by Ki67 immunohistochemistry, is related to poor patient prognosis in many different tumor types. Ki67 expression shows considerable intratumoral heterogeneity. It is unclear if the TMA format is suitable for the analysis of potentially heterogeneous markers because of the small size of TMA spots. We have analyzed a breast cancer TMA containing 2,517 breast tissues, including 2,222 neoplastic and 295 normal or premalignant samples, for Ki67 labeling index (Ki67 LI) and additional markers with a known relationship to Ki67 LI by immunohistochemistry (ER, PR, Bcl-2, Egfr, p16, p53) and Fluorescence in situ hybridization (HER2, MDM2, CCND1, MYC). A high Ki67 LI was linked to tumor phenotype including grade (p < 0.0001), stage (p < 0.0001), nodal stage (p = 0.0018), and patient prognosis (p < 0.0001), elevated protein levels of p53, p16 and Egfr, reduced levels of Bcl2, ER, and PR (p < 0.0001 each), as well as amplifications of HER2, MYC, CCND1 and MDM2 (p < 0.0001 each). In summary, all expected associations between Ki67 and the analyzed molecular markers could be reproduced with high statistical significance using a TMA containing only one tissue sample per tumor, measuring 0.6 mm in diameter. We conclude that associations with cell proliferation can be reliably analyzed in a TMA format.

Adult↗

PubMed2006

Epithelial growth factor receptor status in primary and recurrent ovarian cancer.

Success of epidermal growth factor receptor (EGFR) targeting agents in different cancer types is related to EGFR gene mutations and/or copy number gains. We investigated the EGFR gene status and protein expression by DNA mutational analysis, fluorescence in situ hybridization (FISH), and immunohistochemistry in tumor tissues from 80 patients with primary and corresponding recurrent ovarian serous carcinomas. The patients were classified into six groups with ascending EGFR gene copy numbers. EGFR amplification and high polysomy (FISH+) was present in a significant fraction of the primary (20%) and recurrent (22%) ovarian carcinomas. On mutational analysis, only one tumor with a silent EGFR mutation was observed, and this was the only carcinoma with high-level amplification. EGFR protein immunoexpression was seen in 28% of primary and 33% of recurrent carcinomas and correlated to amplification in the primary tumors (P = 0.003). In recurrent carcinoma, moderate and strong EGFR expression was associated with amplification (P = 0.034). These molecular events potentially have impact on the responsiveness to EGFR targeting agents in ovarian cancer.

Adult↗

PubMed2006

Comprehensive analysis of the expression of the metastasis-associated gene 1 in human neoplastic tissue.

CONTEXT: The metastasis-associated gene 1 (MTA1) is overexpressed in several human cancers. Recent reports suggest that MTA1 may play a role in cancer progression either through transcription repression and/or hormone receptor interactions. OBJECTIVE: To analyze MTA1 expression levels in a wide variety of human tumors. DESIGN: We used Oncomine, an Internet-based compendium of expression array data, to query more than 90 expression array studies, and we evaluated tissue microarrays composed of more than 3200 samples representing 138 different localized neoplasms. RESULTS: Both analyses show that MTA1 is ubiquitously expressed in benign and malignant tumors. The highest levels of MTA1 expression were observed in diffuse B-cell lymphoma (mean staining intensity, 3.9/4), basal cell carcinomas (3.7/4), and consistently in tumors of neuroendocrine descent such as paraganglioma (3.7/4) and carcinoid tumor (3.1/4). CONCLUSIONS: This study characterizes MTA1 expression for the first time across a broad spectrum of primary tumors, demonstrating expression in both benign and malignant neoplasms in addition to showing an association with neuroendocrine differentiation. We also found evidence that MTA1 expression is associated with tissue invasion but may not be sufficient for the progression to metastatic stages.

Biomarkers, Tumor↗

PubMed2005

Increased apolipoprotein deposits in early atherosclerotic lesions distinguish symptomatic from asymptomatic patients.

OBJECTIVE: Apolipoprotein E (apoE) and apolipoprotein B100 (apoB) are both involved in receptor-mediated uptake of atherogenic lipoproteins by the liver. Inefficient hepatic clearance of these lipoproteins leads to symptomatic atherosclerosis. Using arterial tissue microarrays, we tested the hypothesis that apoE and apoB accumulation in the arterial wall discriminates between patients with symptomatic atherosclerosis and patients who never experienced cardiovascular events. METHODS AND RESULTS: In a postmortem study involving 49 patients (22 patients with symptomatic atherosclerosis), we quantified apolipoprotein deposits in arterial rings obtained from the left main coronary, the common carotid, the common iliac, and the renal artery applying tissue microarray technology and semiquantitative immunohistochemistry. In early atherosclerotic lesions, even before atheroma appeared, symptomatic patients had significantly more arterial apoE and apoB deposits than patients without cardiovascular events (P<0.001). Among the symptomatic patients, those without diabetes had more intense apolipoprotein deposits than diabetics. Large amounts of apoE and apoB were found in advanced atherosclerotic lesions, regardless of the activity of the disease. CONCLUSIONS: Increased apolipoprotein deposits are an early sign of symptomatic atherosclerosis. They may reflect either enhanced retention of atherogenic lipoproteins or impaired local apolipoprotein degradation. The arterial lipoprotein turnover may be different in diabetic patients.

Aged↗

PubMed2005

EphB2 expression across 138 human tumor types in a tissue microarray: high levels of expression in gastrointestinal cancers.

PURPOSE: To comprehensively evaluate ephrin receptor B2 (EphB2) expression in normal and neoplastic tissues. EphB2 is a tyrosine kinase recently implicated in the deregulation of cell-to-cell communication in many tumors. EXPERIMENTAL DESIGN: EphB2 protein expression was analyzed by immunohistochemistry on tissue microarrays that included 76 different normal tissues, >4,000 samples from 138 different cancer types, and 1,476 samples of colon cancer with clinical follow-up data. RESULTS: We found most prominent EphB2 expression in the intestinal epithelium (colonic crypts) with cancer of the colorectum displaying the highest EphB2 positivity of all tumors. Positivity was found in 100% of 118 colon adenomas but in 33.3% of 45 colon carcinomas. EphB2 expression was also observed in 75 tumor categories, including serous carcinoma of the endometrium (34.8%), adenocarcinoma of the esophagus (33.3%), intestinal adenocarcinoma of the stomach (30.2%), and adenocarcinoma of the small intestine (70%). The occasional finding of strong EphB2 positivity in tumors without EphB2 positivity in the corresponding normal cells [adenocarcinoma of the lung (4%) and pancreas (2.2%)] suggests that deregulation of EphB2 signaling may involve up-regulation of the protein expression. In colon carcinoma, loss of EphB2 expression was associated with advanced stage (P < 0.0001) and was an indicator of poor overall survival (P = 0.0098). CONCLUSIONS: Our results provide an overview on the EphB2 protein expression in normal and neoplastic tissues. Deregulated EphB2 expression may play a role in several cancer types with loss of EphB2 expression serving as an indicator of the possible pathogenetic role of EphB2 signaling in the maintenance of tissue architecture of colon epithelium.

Colorectal Neoplasms↗

PubMed2005

Diagnostic evaluation of HER-2 as a molecular target: an assessment of accuracy and reproducibility of laboratory testing in large, prospective, randomized clinical trials.

PURPOSE: To critically assess the accuracy and reproducibility of human epidermal growth factor receptor type 2 (HER-2) testing in outside/local community-based hospitals versus two centralized reference laboratories and its effect on selection of women for trastuzumab (Herceptin)-based clinical trials. EXPERIMENTAL DESIGN: Breast cancer specimens from 2,600 women were prospectively evaluated by fluorescence in situ hybridization (FISH) for entry into Breast Cancer International Research Group (BCIRG) clinical trials for HER-2-directed therapies. RESULTS: HER-2 gene amplification by FISH was observed in 657 of the 2,502 (26%) breast cancers successfully analyzed. Among 2,243 breast cancers with central laboratory immunohistochemistry (10H8-IHC) analysis, 504 (22.54%) showed overexpression (2+ or 3+). Outside/local laboratories assessed HER-2 status by immunohistochemistry in 1,536 of these cases and by FISH in 131 cases. Overall, the HER-2 alteration status determined by outside/local immunohistochemistry showed a 79% agreement rate [kappa statistic, 0.56; 95% confidence interval (95% CI), 0.52-0.60], with FISH done by the central laboratories. The agreement rate comparing BCIRG central laboratory 10H8-IHC and outside/local laboratory immunohistochemistry was 77.5% (kappa statistic, 0.51; 95% CI, 0.46-0.55). Finally, HER-2 status, determined by unspecified FISH assay methods at outside/local laboratories, showed a 92% agreement rate (kappa statistic, 0.83; 95% CI, 0.73-0.93), with FISH done at the BCIRG central laboratories. CONCLUSIONS: Compared with the HER-2 status determined at centralized BCIRG reference laboratories, these results indicate superiority of FISH to accurately and reproducibly assess tumors for the HER-2 alteration at outside/local laboratories for entry to clinical trials.

Biomarkers, Tumor↗

PubMed2005

Expression patterns of potential therapeutic targets in prostate cancer.

Androgen withdrawal is the only effective therapy for patients with advanced prostate cancer, but progression to androgen independence ultimately occurs in almost all patients. Novel therapeutic strategies targeting molecular mechanisms that mediate resistance to hormonal and chemotherapeutic treatment are highly warranted. Here, we aimed to evaluate the expression of potential therapeutic targets in advanced prostate cancer. A tissue microarray (TMA) containing samples from 535 tissue blocks was constructed, including benign prostatic hyperplasia as controls (n = 65), prostatic intraepithelial neoplasia (PIN; n = 78), clinically localized prostate cancers (n = 181), as well as hormone-refractory local recurrences (n = 120) and distant metastases (n = 91). The expression of 13 different proteins was analyzed using immunohistochemistry (Bcl-2, p53, ILK, Syndecan-1, MUC-1, EGFR, HER2/neu, HSP-90, Ep-CAM, MMP-2, CD-10, CD-117 and Ki67). Significant overexpression in hormone-refractory prostate cancer and metastatic tissue compared to localized prostate cancer was found for Ki67 (64% vs. 9%), Bcl-2 (11% vs. 1%), p53 (35% vs. 4%), Syndecan-1 (38% vs. 3%), EGFR (16% vs. 1%) and HER2/neu (16% vs. 0%). Overexpression of CD-117 was restricted to 1 single metastasis. All other markers did not show relevant differences in expression between subgroups. Taken together, p53, Bcl-2, Syndecan-1, EGFR and HER2/neu are preferentially expressed in hormone-refractory and metastatic prostate cancer. Selected inhibition of these targets might offer a strategy to treat advanced tumors and prevent further progression. Treatment decisions should not be based on findings in primary tumors but rather on tissues from recurrent or metastatic lesions.

Adenocarcinoma↗

PubMed2005

Predominance of high-grade pathway in breast cancer development of Middle East women.

Recent data have suggested considerable molecular differences in cancers from various ethnical groups. As molecular features are increasingly used for predicting cancer prognosis and response to therapy, better knowledge of ethnic molecular features is important. To identify potential molecular differences between breast cancers in Europe and the Middle East, we analyzed consecutive breast cancer series from Switzerland (n=2197) and Saudi Arabia (n=204). Tissue microarrays were analyzed by fluorescence in situ hybridization for HER2, CCND1, MYC, and EGFR amplification. The data revealed marked differences between Saudi and Swiss patients. Saudi breast cancers had a markedly higher frequency of HER2 (31 vs 17%; P<0.0001) and MYC (16 vs 5%; P<0.0001) amplifications than Swiss breast cancers. Remarkably, this was partly due to a much higher incidence of grade 3 cancers in the Saudi than in the Swiss population (65 vs 32%; P<0.0001). However, differences in amplification frequency hold also true within grade 3 cancers (HER2: 40 vs 30%, P<0.05; MYC: 22 vs 11%, P=0.002). Interestingly, in combination with known age standardized incidence rates of breast cancer in Saudi Arabia (21.6/100 000) and Switzerland (70.1/100 000), these data suggest that the incidence of high-grade breast cancer is comparable for Saudi and Swiss women, while the incidence of low-grade breast cancers is about 14 times lower in Saudi than for Swiss women. These observations suggest that a difference in genetic susceptibility and/or lifestyle between Saudi and Swiss women has a substantial and much higher than expected impact on the risk of low-grade breast cancer.

Adult↗

PubMed2005

Tissue microarrays.

New high-throughput screening technologies have led to the identification of hundreds of genes with potential roles in cancer or other diseases. For evaluation of promising candidate genes, however, in-situ analysis of high numbers of clinical tissue samples is mandatory. The tissue microarray (TMA) technology greatly facilitates such analysis. In this method minute tissue samples (0.6 mm in diameter) from up to 1000 different tissues can be analyzed on one microscope glass slide. All in-situ methods suitable for histological studies can be applied to TMAs without major changes in protocols, including immunohistochemistry, fluorescence in-situ hybridization, or RNA in-situ hybridization. Because all tissues are analyzed simultaneously with the same batch of reagents, TMA studies provide an unprecedented degree of standardization, speed, and cost efficiency.

Humans↗

PubMed2004

Prognostic relevance of gene amplifications and coamplifications in breast cancer.

Multiple different oncogenes have been described previously to be amplified in breast cancer including HER2, EGFR, MYC, CCND1, and MDM2. Gene amplification results in oncogene overexpression but may also serve as an indicator of genomic instability. As such, presence of one or several gene amplifications may have prognostic significance. To assess the prognostic importance of amplifications and coamplifications of HER2, EGFR, MYC, CCND1, and MDM2 in breast cancer, we analyzed a breast cancer tissue microarray containing samples from 2197 cancers with follow-up information. Fluorescence in situ hybridizations revealed amplifications of CCND1 in 20.1%, HER2 in 17.3%, MDM2 in 5.7%, MYC in 5.3%, and EGFR in 0.8% of the tumors. All gene amplifications were significantly associated with high grade. HER2 (P < 0.001) and MYC amplification (P < 0.001) were also linked to shortened survival. In case of HER2, this was independent of grade, pT, and pN categories. MYC amplification was almost 3 times more frequent in medullary cancer (15.9%), than in the histologic subtype with the second highest frequency (ductal; 5.6%; P = 0.0046). HER2 and MYC amplification were associated with estrogen receptor/progesterone receptor negativity (P < 0.001) whereas CCND1 amplification was linked to estrogen receptor/progesterone receptor positivity (P < 0.001). Coamplifications were more prevalent than expected based on the individual frequencies. Coamplifications of one or several other oncogenes occurred in 29.6% of CCND1, 43% of HER2, 55.7% of MDM2, 65% of MYC, and 72.8% of EGFR-amplified cancers. HER2/MYC-coamplified cancers had a worse prognosis than tumors with only one of these amplifications. Furthermore, a gradual decrease of survival was observed with increasing number of amplifications. In conclusion, these data support a major prognostic impact of genomic instability as determined by a broad gene amplification survey in breast cancer.

Breast Neoplasms↗

PubMed2004

Prevalence of KIT expression in human tumors.

PURPOSE: KIT is a target for imatinib mesylate (Gleevec; Novartis Pharma, Basel, Switzerland). Gastrointestinal stromal tumors (GISTs) express KIT and respond favorably to imatinib therapy. To determine other tumors in which such a molecular targeted therapy might be indicated, we investigated KIT expression in different human tumor types. Because recent studies in GISTs suggest that KIT-activating mutations predict response to imatinib therapy, we also sequenced a subset of positive tumors. MATERIALS AND METHODS: More than 3,000 tumors from more than 120 different tumor categories were analyzed by immunohistochemistry in a tissue microarray format. Seven commercially available anti-KIT antibodies were initially evaluated. The antibody A4502 (DAKO) was selected for analysis because of a high frequency of positivity in GIST and low staining background in other tissues. To determine the frequency of KIT mutations in various tumor types, the exons 2, 8, 9, 11, 13, and 17 (where mutations previously were reported) were sequenced in 36 tumors with strong KIT expression. RESULTS: KIT positivity was detected in 28 of 28 GISTs (100%), 42 of 50 seminomas (84%), 34 of 52 adenoid-cystic carcinomas (65%), 14 of 39 malignant melanomas (35%), and eight of 47 large-cell carcinomas of the lung (17%), as well as in 47 additional tumor types. KIT mutations were found in six of 12 analyzed GISTs, but only in one of 24 other tumors. CONCLUSION: The results suggest that KIT expression occurs infrequently in most tumor types and that, with the exception of GISTs, KIT gene mutations are rare in immunohistochemically KIT-positive tumors.

Antineoplastic Agents↗

PubMed2004

Expression and amplification of therapeutic target genes in retinoblastoma.

PURPOSE: We set out to evaluate alterations of the therapeutic target genes KIT (CD 117), EGFR, and HER-2 in human retinoblastoma. METHODS: Ninety-five formalin-fixed, paraffin-embedded retinoblastomas were brought into a tissue microarray (TMA) format. Immunohistochemistry was performed to analyze the expression of CD117, EGFR, and HER-2. Fluorescence in situ hybridization (FISH) was utilized for detection of EGFR amplifications. Three tumors with strong CD117 positivity were sequenced for KIT exon 11 mutations. RESULTS: Detectable CD117 expression was seen in 19% of all interpretable cases. Sequence analysis of the three tumors with the strongest CD117 expression revealed no mutations. EGFR was positive in 14% of all cases. No EGFR amplification was observed by FISH, however. All tumors were negative for HER-2 expression. CONCLUSIONS: Our data suggest that selected cases of retinoblastoma may be candidates for anti-EGFR and imatinib mesylate (STI571) therapy.

Adolescent↗

PubMed2004

Arterial neovascularization and inflammation in vulnerable patients: early and late signs of symptomatic atherosclerosis.

BACKGROUND: Atherosclerosis is complicated by cardiovascular events such as myocardial infarction, stroke, or peripheral arterial occlusive disease. Inflammation and pathological neovascularization are thought to precipitate plaque rupture or erosion, both causes of arterial thrombosis and cardiovascular events. We tested the hypothesis that arterial inflammation and angiogenic events are increased throughout the arterial tree in vulnerable patients, ie, in patients who suffered from cardiovascular events, compared with patients who never suffered from complications of atherosclerosis. METHODS AND RESULTS: In a postmortem study, we quantified the inflammatory infiltrate and microvascular network in the arterial wall of iliac, carotid, and renal arteries. Tissue microarray technology was adapted to investigate full-thickness arterial sectors. We compared 22 patients with symptomatic atherosclerosis with 27 patients who never had suffered from any cardiovascular event. The absolute intimal macrophage content was 2- to 4-fold higher in vulnerable patients at all 3 arterial sites analyzed (P<0.05). Patients with symptomatic atherosclerosis had a denser network of vasa vasorum than patients with asymptomatic disease (33+/-2 versus 25+/-2 adventitial microvessels per 1 mm2; P=0.008). Hyperplasia of vasa vasorum was an early and macrophage infiltration was a late sign of symptomatic atherosclerosis. CONCLUSIONS: High intimal macrophage content and a hyperplastic network of vasa vasorum characterize vulnerable patients suffering from symptomatic atherosclerosis. These changes are uniformly present in different arterial beds and support the concept of symptomatic atherosclerosis as a panarterial disease.

Aged↗

PubMed2004

Impaired expression of the cell cycle regulator BTG2 is common in clear cell renal cell carcinoma.

The prognosis of patients with renal cell carcinoma (RCC) is poor. A full understanding of the molecular genetics and signaling pathways involved in renal cancer development and in the metastatic process is of central importance for developing innovative and novel treatment options. In this study, BD Atlas Human Cancer 1.2 cDNA microarrays were used to identify genes involved in renal tumorigenesis. By analyzing gene expression patterns of four clear cell RCC (cRCC) cell lines and normal renal tissue, 25 genes were found differentially expressed. To determine the relevance of these genes, RNA in situ hybridization was performed on a tissue microarray generated from 61 snap-frozen primary renal cell carcinomas and 12 normal renal cortex biopsies. B-cell translocation gene 2 (BTG2), a negative cell cycle regulator, which was expressed in normal renal tissue but down-regulated in cRCC cell lines and primary cRCCs, was selected for additional experiments. Quantitative BTG2 mRNA expression analysis in 42 primary cRCCs and 18 normal renal cortex biopsies revealed up to 44-fold reduced expression in the tumor tissues. Decrease of BTG2 expression was not associated with tumor stage, grade, and survival. Cell culture experiments demonstrated that BTG2 expression was weakly inducible by the phorbolester 12-O-tetradecanoylphorbol-13-acetate in one of four cRCC cell lines. In contrast, increasing cell density led to elevated BTG2 mRNA expression in three of four cRCC cell lines. In both experiments, BTG2 mRNA levels did not reach values observed in normal renal tissue. These data suggest that down-regulation of BTG2 is an important step in renal cancer development.

Adenocarcinoma, Clear Cell↗

PubMed2004

KIT (CD117)-positive breast cancers are infrequent and lack KIT gene mutations.

PURPOSE: KIT (CD117) is a transmembrane tyrosine kinase representing a target for STI571 (Glivec) therapy. Some KIT-overexpressing solid tumors have responded favorably to STI571, potentially because of the presence of KIT-activating mutations. EXPERIMENTAL DESIGN: To investigate the epidemiology of KIT overexpression and mutations, we investigated a series of 1654 breast cancers. All tumors were analyzed by immunohistochemistry in a tissue microarray format. RESULTS: KIT expression was always present in normal breast epithelium. However, cancer analysis revealed the only 43 of 1654 (2.6%) tumors were KIT-positive. KIT expression was more frequent in medullary cancer (9 of 47 positive; 19.1%) than in any other histological tumor subtype (P < 0.001). KIT expression was significantly associated with high tumor grade (P < 0.0001) but unrelated to pT and pN categories or patient survival. Mutation analysis of exons 2, 8, 9, 11, 13, and 17 was negative in 10 KIT-positive tumors. CONCLUSIONS: Overall, our data show that a high level of KIT expression occurs infrequently in breast cancer. KIT-positive breast cancers may not reflect "KIT up-regulation" because KIT is also expressed in normal breast epithelium. The lack of KIT mutations also argues against the therapeutic efficacy of STI571 in breast cancer.

Adult↗

PubMed2004

Frequent EpCam protein expression in human carcinomas.

Expression of the transmembrane glycoprotein EpCam (epithelial cellular adhesion molecule) occurs in normal epithelium of different organs and was described in carcinomas of various sites. Specific anti-EpCam therapies are now being used in clinical trials. Thus, it is of interest to know which tumor types express or overexpress this protein, and in what frequency. We therefore analyzed EpCam expression by immunohistochemistry on a tissue microarray containing 3900 tissue samples of 134 different histological tumor types and subtypes. EpCam expression was detected in 98 of 131 tumor categories. At least a weak EpCam expression in >10% of tumors was observed in 87 of 131 different tumor categories. Adenocarcinomas of the colon (81%) and pancreas (78%), as well as hormone-refractory adenocarcinomas of the prostate (71%), were identified as particularly promising therapy targets with a high fraction of strongly positive tumors. Most soft-tissue tumors and all lymphomas were EpCam negative. It is concluded that anti-EpCam therapies, if proven to be successful, will have broad applications in a wide variety of carcinomas.

Adenocarcinoma↗