Biomedical subjects

Marcel Bundi

Publications and source records attributed to Marcel Bundi.

4 recordsLinked to original sources

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

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↗

PubMed2004

The homeobox intestinal differentiation factor CDX2 is selectively expressed in gastrointestinal adenocarcinomas.

CDX2 is a homeobox domain-containing transcription factor that is important in the development and differentiation of the intestines. Based on recent studies, CDX2 expression is immunohistochemically detectable in normal colonic enterocytes and is retained in most, but not all, colorectal adenocarcinomas. CDX2 expression has also been documented in a subset of adenocarcinomas arising in the stomach, esophagus and ovary. In this study, we examined CDX2 expression in a series of large tissue microarrays representing 4652 samples of normal and neoplastic tissues. Strong nuclear staining for CDX2 was observed in 97.9% of 140 colonic adenomas, 85.7% of 1109 colonic adenocarcinomas overall and 81.8% of 55 mucinous variants. There was no significant difference in the staining of well-differentiated (96%) and moderately differentiated tumors (90.8%, P=0.18), but poorly differentiated tumors showed reduced overall expression (56.0%, P<0.000001). Correspondingly, there was an inverse correlation between CDX2 expression and tumor stage, with a significant decrease in staining between pT2 and pT3 tumors (95.8 vs 89.0%, P<0.012), and between pT3 and pT4 tumors (89.0 vs 79.8%, P<0.016). Analysis of 140 locally advanced, CDX2-positive colorectal adenocarcinomas coarrayed with their matching lymph node metastases revealed that expression of this marker was retained in 82.1% of the metastases. Consistent with previous reports, CDX2 staining was observed in gastric adenocarcinomas (n=71), more commonly in the intestinal-type than the diffuse-type (28.9 vs 11.5%, P<0.05). Occasional ovarian carcinomas were positive for CDX2, including mucinous (10.5%), endometrioid (9.3%) and serous variants (2%), but expression was either very rare or absent in primary carcinomas of the lung, breast, thyroid, pancreas, liver, gallbladder, kidney, endometrium and urinary bladder. A low frequency of CDX2 expression in pancreatic and biliary carcinomas observed on the microarrays was pursued further by comparing these tumors with ampullary adenocarcinomas on conventional sections. Ampullary adenocarcinomas were more commonly positive for CDX2 (19/24, 79%) than cholangiocarcinomas (1/11, 9%) and pancreatic carcinomas (3/20, 15%). In summary, CDX2 is a sensitive and specific marker for colorectal adenocarcinoma, although its expression is decreased among higher grade and stage tumors, and it is not invariably present in metastases from positive primaries. CDX2 may also be helpful in distinguishing adenocarcinomas of the ampulla from those arising in the pancreas and biliary tree.

Adenocarcinoma↗

PubMed2004

Hepatocyte paraffin 1 expression in human normal and neoplastic tissues: tissue microarray analysis on 3,940 tissue samples.

Hepatocyte paraffin 1 (Hep Par 1) is a monoclonal antibody developed from hepatic tissue from a failed liver allograft. Several studies have shown that Hep Par 1 is a useful marker to differentiate hepatocellular carcinoma (HCC) from other types of adenocarcinoma metastatic to the liver. The aim of our study was the systematic investigation of the epidemiology of Hep Par 1 expression in 3,940 tissue samples using the tissue microarray technique. Strong Hep Par 1 expression was found most frequently in 35 (73%) of 48 HCCs. In nonhepatic tumors, strong Hep Par 1 expression was detected in adenocarcinoma of the lung (2/50), gallbladder (3/31), pancreas (2/48), stomach (3/74), small intestine (1/11), adenoma of the colon with high-grade dysplasia (1/49), adrenal gland carcinoma (1/6), paraganglioma (1/9), and malignant melanoma (2/48). Our data suggest that Hep Par 1 is a highly specific marker for HCC, although several nonhepatic tumors occasionally can show some Hep Par 1 positivity.

Adenocarcinoma↗