Comparison of loss of heterozygosity and microsatellite instability in adenocarcinomas of the distal esophagus and proximal stomach.

Adenocarcinoma of the gastroesophageal junction is rapidly rising in incidence. It has been proposed that these tumors be classified as three different types: distal esophageal (AEG I), cardia (AEG II), and subcardia (AEG III). Using comparative genomic hybridization (CGH) analysis, one recent study reported that the 14q chromosomal arm showed a significantly higher rate of deletion in esophageal than in cardia adenocarcinoma.

Chromosomal changes during development and progression of prostate adenocarcinomas.

Chromosomal copy number changes were investigated in 16 prostate carcinomas, 12 prostatic intraepithelial neoplasias (PIN; 4 low-grade and 8 high-grade) adjacent to the invasive tumour areas, and 5 regional lymph node metastases. For this purpose, comparative genomic hybridization (CGH) was performed and a copy number karyotype for each histomorphological entity was created. CGH on microdissected cells from non-neoplastic glands was carried out on 3 different cases to demonstrate the reliability of the overall procedure.

Quantitative gene expression analysis in microdissected archival formalin-fixed and paraffin-embedded tumor tissue.

Formalin-fixed, paraffin-embedded tissue is the most widely available material for retrospective clinical studies. In combination with the potential of genomics, these tissues represent an invaluable resource for the elucidation of disease mechanisms and validation of differentially expressed genes as novel therapeutic targets or prognostic indicators. We describe here an approach that, in combination with laser-assisted microdissection allows quantitative gene expression analysis in formalin-fixed, paraffin-embedded archival tissue.

Loss of heterozygosity and microsatellite instability as predictive markers for neoadjuvant treatment in gastric carcinoma.

We analyzed a group of gastric carcinomas treated with a cisplatin-based neoadjuvant chemotherapy regimen for microsatellite instability (MSI) and loss of heterozygosity (LOH) to determine whether there is any relation between microsatellite alterations and therapy response. Pretherapeutic endoscopic biopsies of 37 patients were studied at 11 microsatellite loci. Thirteen (35%) had a complete or partial clinical response (responders), and 24 (65%) had only a minor or no response (nonresponders).

[Current classification of gastrointestinal stromal tumors].

Gastrointestinal mesenchymal tumors traditionally have been designated as smooth muscle tumors. However, with increasingly accurate analytic tools most investigators were unable to demonstrate true myogenic differentiation. Diagnostic criteria and grading vary among different studies and the biological behavior of these gastrointestinal stromal tumors (GIST) is difficult to predict.

Endoscopic ultrasound criteria for vascular invasion in the staging of cancer of the head of the pancreas: a blind reevaluation of videotapes.

Background: It has been claimed in several prospective studies that endoscopic ultrasonography (EUS) is highly accurate in the locoregional staging of pancreatic cancer. However, the value of the EUS criteria for the diagnosis of vascular involvement is less well established. To totally exclude potential bias introduced by the availability of prior information, a completely blinded analysis of videotapes of patients with cancer of the pancreatic head was therefore conducted.

Evaluation of c-erbB-2 overexpression and Her-2/neu gene copy number heterogeneity in Barrett's adenocarcinoma.

Amplification of the Her-2/neu gene is accompanied by overexpression of its cell surface receptor product, c-erbB-2 protein. To investigate the degree of intratumoural heterogeneity we applied immunohistochemistry in primary Barrett's adenocarcinoma (BCA) (n = 6) and dysplasia adjacent to the carcinoma (n = 4). In addition, fluorescence in situ hybridisation (FISH) was performed in primary BCA (n = 5) and dysplastic areas (n = 4).

Heterogeneous chromosomal aberrations in intraductal breast lesions adjacent to invasive carcinoma.

There is evidence that breast cancer is a heterogeneous disease phenotypically as well as molecular biologically. So far, heterogeneity on the molecular biological level has not been investigated in potential precursor lesions, such as ductal hyperplasia (DH) and ductal carcinoma in situ (DCIS). In this study we applied comparative genomic hybridization (CGH) to formalin-fixed, paraffin-embedded breast tissue with DH and DCIS, adjacent to invasive ductal carcinoma (IDC), to screen these potential precursor lesions for whole genomic chromosomal imbalances.

Quality assessment in diagnostic molecular pathology: experience from a German-Austrian-Swiss multicenter trial.

In order to assess the current technical standard of diagnostic molecular pathology, we have conducted a multicenter trial with 34 participating pathology laboratories in Germany, Austria and Switzerland. Formalin-fixed, paraffin-embedded tissue blocks were selected from 15 cases, comprising 4 B-cell non-Hodgkin's lymphomas, 4 T-cell non-Hodgkin lymphomas, 4 cases with lymphadenitis, 2 cases with confirmed tuberculosis and 1 case of sarcoidosis. All participating laboratories received one 10-microm section from each of the 15 cases to detect clonality using immunoglobulin heavy chain (IgH) gene or T-cell receptor (TCR)-gamma gene rearrangement analysis in 12 and mycobacterial DNA in 3 cases.

Comparison of different histopathological methods for the examination of sentinel lymph nodes in breast cancer.

Background: Sentinel lymphonodectomy is a new method for the classification of axillary lymph nodes in breast cancer. The optimum technique for the pathological examination of sentinel lymph nodes (SLNs) is still under debate.

Materials And Methods: Different histopathological techniques were evaluated in order to study their diagnostic accuracy regarding the detection of metastases in 49 SLNs of 40 breast cancer patients.

Stromelysin-3 expression in noninvasive and invasive neoplasms of the urinary bladder.

Stromelysin-3 (ST-3) is a protease frequently expressed by fibroblasts surrounding invasive carcinomas. Based on its expression in some cases of breast carcinoma-in-situ, it has been thought to indicate a higher likelihood for subsequent invasion in preinvasive lesions. Carcinoma-in-situ (pTis) and noninvasive papillary tumor (pTa) of the urinary bladder are preinvasive lesions with an uncertain potential to become invasive.

Molecular genetic changes in metastatic primary Barrett's adenocarcinoma and related lymph node metastases: comparison with nonmetastatic Barrett's adenocarcinoma.

Lymph node metastasis is one of the strongest negative prognostic factors for patients with Barrett's adenocarcinoma (BCA). However, despite the importance of the metastatic process in BCA, the molecular basis of it remains poorly understood. To search for cytogenetic events associated with metastasis in regional or distant lymph nodes in BCA, we investigated 8 primary BCA and their lymph node metastases and compared them with 18 nonmetastatic BCA.

Kinetic profiles of intraepithelial and invasive prostatic neoplasias: the key role of down-regulated apoptosis in tumor progression.

The cell kinetic of prostatic intraepithelial neoplasia (PIN) is poorly understood. Herein we report the kinetic pattern of PIN, both not associated (primary) and associated (secondary) with coexistent invasive carcinoma (PCa). Surgical specimens collected in 20 cases of primary PIN, 20 of secondary PIN and 20 of PCa were studied by MIB-1 immunostaining, in situ end-labeling (ISEL) and DNA histogram analysis, and the cell density in each case was estimated using the formula N = (n pi/4)2.

Molecular analysis of E-cadherin and cadherin-11 in Wilms' tumours.

Different studies of Wilms' tumours have demonstrated a loss of heterozygosity (LOH) of chromosome 16q ranging from 17 to 25%. In order to search for a potential tumour suppressor gene on 16q, we chose the calcium-dependent cell adhesion molecules E-cadherin and cadherin-11 as candidate genes, which are both located on the long arm of chromosome 16. E-cadherin is known to be expressed in epithelial structures, whereas cadherin-11 is supposed to be expressed in mesenchymal structures and developing epithelium, including renal tubules.

Microdissection of tissue sections: application to the molecular genetic characterisation of premalignant lesions.

The characterisation of the early molecular genetic events of tumor development depends on the selective procurement of histopathologically defined small cell populations from premalignant tissue. In order to obtain high-quality DNA, mRNA and proteins from these small tissue samples and even from single cells, tissue microdissection is one of the most useful techniques, becoming increasingly important for molecular pathologists. Using different microdissection techniques which allow the isolation of morphologically defined cell populations under direct visualisation, it is now feasible to study molecular genetic events that drive the multistep evolution in tumours.

Tumor-derived mutated E-cadherin influences beta-catenin localization and increases susceptibility to actin cytoskeletal changes induced by pervanadate.

E-cadherin participates in homophilic cell-to-cell adhesion and is localized to intercellular junctions of the adherens type. In the present study, we investigated the localization of adherens junction components in cells expressing mutant E-cadherin derivatives which had been previously cloned from diffuse-type gastric carcinoma. The mutations are in frame deletions of exons 8 or 9 and a point mutation in exon 8 and affect the extracellular domain of E-cadherin.

Increasing chromosome 1 copy number parallels histological progression in breast carcinogenesis.

Chromosome 1 copy number in the benign breast lesions hyperplasia and atypical duct hyperplasia (ADH) was investigated using fluorescence in situ hybridization on paraffin sections. Progression of chromosome 1 changes occurring in parallel with histological progression from normal through hyperplasia and ADH to ductal carcinoma in situ (DCIS) and invasive carcinoma was also assessed, both overall and within individual patients. The mean signal number for normal cells was 1.

Tumor-associated overexpression of the soluble T1-S receptor in lymph node-negative breast cancer.

The oncogene-inducible secreted T1-S glycoprotein is overexpressed in invasive breast carcinomas in mice. As yet, nothing is known about the expression of T1-S in spontaneously occurring human cancers. A report follows on the overexpression of T1-S mRNA in 67% of primary invasive lymph node-negative breast carcinomas (31 of 46 patients) as determined by quantitative reverse transcriptase polymerase chain reaction.

Accumulation of chromosomal imbalances from intraductal proliferative lesions to adjacent in situ and invasive ductal breast cancer.

Carcinoma of the breast is thought to evolve through a sequential progression from normal to proliferative epithelium and eventually into carcinoma. Here lumpectomy specimens from five patients were studied, selected for the presence of ductal hyperplasia without atypia, atypical ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma. Laser microdissection of tissue allowed precise sampling and direct correlation of phenotypic and genotypic changes.

[Novel mutation-specific monoclonal E-cadherin antibodies make possible allele differentiation at the protein level in tumors].

Somatic deletion mutations in the cell adhesion molecule E-cadherin are present in almost 50% of diffuse type gastric cancer. We recently generated monoclonal antibodies against an in-frame deletion of exon 9. The aim of this study was to generate and characterize monoclonal antibodies against the second mutational hot spot, in-frame deletions of exon 8.

[Diffuse stomach carcinoma: from H&E diagnosis and molecular pathology to specific therapy].

E-cadherin is a homophilic cell adhesion molecule that is mutated in half of diffuse-type gastric cancer patients. Since these mutations generally affect the extracellular portion of the transmembrane molecule and do not interrupt the reading frame, altered E-cadherin protein may be an excellent tumor marker. We established a rapid PCR-based E-cadherin mutation detection technique allowing positive results within a day.

[Are there differences between ex adenoma and de novo colorectal carcinomas?].

Colorectal carcinoma is a major cause of death throughout the Western world. It is increasingly recognized that any reduction in mortality must be achieved through the detection and removal of early and precancerous lesions. The primary attention for such a preventive strategy has been the polypoid adenoma and surveillance studies have shown a significant reduction in the incidence of carcinoma through systematic polypectomy of suspicious lesions.