Low frequency of molecular changes and tumor recurrence in inverted papillomas of the urinary tract.

Aim: Inverted papilloma (IP) of the urinary tract can be difficult to distinguish from noninvasive urothelial carcinoma with prominent inverted growth pattern (invNIUC). Ancillary markers may help to resolve such cases and clarify the reported malignant potential of some IPs.

Methods: Eighty-nine urothelial lesions initially diagnosed as IP were reviewed by 4 experienced urologic pathologists and studied immunohistochemically (Ki67, p53, CK20, MSH2, MLH1, and MSH6).

Marked gene transcript level alterations occur early during radical prostatectomy.

Objectives: Gene expression analyses have become an important approach to understand the biology of cancer. However, transcript level patterns and RNA quality could rapidly change in response to ischemic and mechanical stress. Studies have shown that this occurs both perioperatively and after surgical removal of organs.

Integrative genomic analysis of small-cell lung carcinoma reveals correlates of sensitivity to bcl-2 antagonists and uncovers novel chromosomal gains.

Cancer is a highly heterogeneous disease in terms of the genetic profile and the response to therapeutics. An early identification of a genomic marker in drug discovery may help select patients that would respond to treatment in clinical trials. Here we suggest coupling compound screening with comparative genomic hybridization analysis of the model systems for early discovery of genomic biomarkers.

Estrogen receptor alpha (ESR1) gene amplification is frequent in breast cancer.

Using an Affymetrix 10K SNP array to screen for gene copy number changes in breast cancer, we detected a single-gene amplification of the ESR1 gene, which encodes estrogen receptor alpha, at 6q25. A subsequent tissue microarray analysis of more than 2,000 clinical breast cancer samples showed ESR1 amplification in 20.6% of breast cancers.

Close association between HER-2 amplification and overexpression in human tumors of non-breast origin.

The relationship between HER-2 overexpression and gene amplification is well evaluated in breast cancers but remains unclear or controversial in many other tumor entities. Therefore, we tested the HER-2 status in more than 120 different tumor entities. 5751 tumor samples were analyzed on TMAs by immunohistochemistry (Hercept-Test, DAKO) and fluorescence in situ hybridization (PathVysion, Abbott-Vysis) under highly standardized conditions.

Similar patterns of loss of heterozygosity in serum of adenocarcinoma of the distal oesophagus and the cardia in early diagnosis.

Background: Loss of heterozygosity (LOH) may be a valuable tool for detection of malignant proceedings. The aim of our study was to investigate LOH in the serum of patients with adenocarcinoma of the distal oesophagus and the cardia for diagnostic and prognostic utility.

Patients And Methods: Matched tumour and serum samples from 46 surgically treated patients with oesophageal adenocarcinoma and cardia carcinoma divided in two groups were analysed.

Molecular staging of prostate cancer in the year 2007.

Numerous attempts towards improving patient management by molecular staging have been fruitless so far. No single molecular parameter is routinely analyzed in prostate cancer tissue. This may be partly due to genuine properties of prostate cancer that may make this tumor a difficult target.

Prognostic value of cell cycle and apoptosis regulatory proteins in mismatch repair-proficient colorectal cancer: a tissue microarray-based approach.

Cell cycle and apoptosis regulatory proteins are markers of tumor progression in colorectal cancer. In a series of 1,274 mismatch repair-proficient colorectal cancers, immunohistochemical analysis of p21, p27, p53, and bcl-2 expression was performed using the tissue microarray technique. In univariate analysis, p21 expression was associated with tumor location and pN0; p27 expression with tumor location, lower tumor grade, early pT, and pN; p53 expression with tumor location; and bcl-2 with early pT and pN.

Frequent homogeneous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus.

HER-2 is the target for antibody based treatment of breast cancer (Herceptin). In order to evaluate the potential role of such a treatment in esophageal cancers, HER-2 amplification and overexpression was investigated in primary and metastatic cancers of the esophagus. A tissue microarray was constructed from 255 primary esophageal cancers (110 adenocarcinomas and 145 squamous cell carcinomas), 89 nodal and 33 distant metastases.

Abundant expression of AMACR in many distinct tumour types.

Aims: Alpha-methylacyl-CoA racemase (AMACR), a mitochondrial and peroxisomal enzyme, is a valuable tool to confirm the diagnosis of prostate cancer, especially if combined with basal cell markers. To extend this diagnostic utility to other neoplasias, we comprehensively surveyed AMACR expression in human tumours.

Methods: We performed immunohistochemical analyses on tissue microarrays of AMACR expression in over 125 different human tumour types and 80 normal tissues.

DACH1 is a cell fate determination factor that inhibits cyclin D1 and breast tumor growth.

Obstacles to the expansion of cells with proliferative potential include the induction of cell death, telomere-based senescence, and the pRb and p53 tumor suppressors. Not infrequently, the molecular pathways regulating oncogenesis recapitulate aberrations of processes governing embryogenesis. The genetic network, consisting of the dachshund (dac), eyes absent (eya), eyeless, and sine oculis (so) genes, regulates cell fate determination in metazoans, with dac serving as a cointegrator through a So DNA-binding factor.

Microsatellite DNA alterations of gastrointestinal stromal tumors are predictive for outcome.

Purpose: In gastrointestinal stromal tumors (GIST), loss of heterozygosity (LOH) on chromosome 22 and its presumptive biological function has been described. The prognostic value of these and other DNA regions for patient survival remains unclear.

Experimental Design: Sixty patients who underwent surgery at our institution between 1992 and 2003 for GIST were histopathologically reclassified by immunohistochemistry and the GIST consensus group criteria 2001.

Friend leukaemia integration-1 expression in malignant and benign tumours: a multiple tumour tissue microarray analysis using polyclonal antibody.

Background: Friend leukaemia integration-1 (FLI-1) antibody is a useful marker for Ewing's sarcoma/primitive neuroectodermal tumour (EWS/PNET) and vascular tumours. However, it is also expressed in subsets of lymphoblastic lymphoma, Merkel cell carcinoma (MCC) and desmoplastic small round cell tumour (DSRCT).

Aim: To determine expression of FLI-1 in various benign and malignant neoplasms, by immunohistochemical analysis on 4323 tumours using multiple tumour microarrays, as well as on whole sections.

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.

Pax-5 immunoexpression in various types of benign and malignant tumours: a high-throughput tissue microarray analysis.

Background: Pax-5 belongs to the Pax gene family transcription factors that play an important role in organogenesis and in B cell ontogeny. It is expressed in B cell non-Hodgkin's lymphoma (B-NHL), Hodgkin's lymphoma (HL) and neuroendocrine carcinomas. However, its expression in other tumour types is not fully explored.

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.

High frequency and strong prognostic relevance of O6-methylguanine DNA methyltransferase silencing in diffuse large B-cell lymphomas from the Middle East.

Several clinically relevant molecular classifiers of diffuse large B-cell lymphoma (DLBCL) have recently been demonstrated in Western populations. However, substantial molecular differences have recently been shown between tumors derived from different ethnic groups. To investigate prevalence and interrelationship of recently suggested molecular prognostic markers in Middle East DLBCL, we analyzed coexpression of CD10/Bcl6 (by immunohistochemistry), t(14;18) translocations (by fluorescence in situ hybridization), and methylation of the gene encoding the DNA repair enzyme O(6)-methylguanine DNA methyltransferase (MGMT) in a series of 190 DLBCL patients from Saudi Arabia with clinical follow-up data.

High incidence of EMMPRIN expression in human tumors.

Extracellular matrix metalloproteinase inducer expressed by tumor cells stimulates peritumoral fibroblasts to produce matrix metalloproteinases, thus contributing to tumor invasion and metastasis. To assess its suitability as potential therapeutic target, the overall incidence of EMMPRIN expression in normal and neoplastic tissues was analyzed. EMMPRIN expression was detected immunohistochemically using monoclonal antibodies MEM-M6/1 and HIM6 and tissue microarrays with 2,348 and 608 tissue samples from 129 distinct tumor types and 76 different normal tissues, respectively.

High throughput tissue microarray analysis of FHIT expression in diffuse large cell B-cell lymphoma from Saudi Arabia.

Recent studies have suggested a potential prognostic role of alterations of the fragile histidine triad (FHIT) gene in diffuse large B-cell lymphoma. To evaluate possible mechanisms of FHIT inactivation and to further clarify its potential prognostic relevance, we analyzed a set of 114 diffuse large B-cell lymphoma with clinical follow-up information. Tissue microarrays were analyzed by immunohistochemistry for protein expression, and corresponding DNA samples were analyzed for FHIT promotor hypermethlyation.

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.

Epstein-Barr virus infection is not the sole cause of high prevalence for Hodgkin's lymphoma in Saudi Arabia.

The age-adjusted incidence of Hodgkin's lymphoma (HL) is markedly higher in Saudi Arabia than in the USA, and accounts for 10.5% of all neoplasias in children aged 15 years or older in Saudi Arabia. Epstein-Barr virus (EBV) infection has been suspected to cause high HL incidence in developing countries.

SOX4 expression in bladder carcinoma: clinical aspects and in vitro functional characterization.

The human transcription factor SOX4 was 5-fold up-regulated in bladder tumors compared with normal tissue based on whole-genome expression profiling of 166 clinical bladder tumor samples and 27 normal urothelium samples. Using a SOX4-specific antibody, we found that the cancer cells expressed the SOX4 protein and, thus, did an evaluation of SOX4 protein expression in 2,360 bladder tumors using a tissue microarray with clinical annotation. We found a correlation (P < 0.

High epidermal growth factor receptor amplification rate but low mutation frequency in Middle East lung cancer population.

Epidermal growth factor receptor (EGFR) exon 18-21 mutations were shown to be highly predictive of response to gefitinib (Iressa) therapy in lung cancer. Studies on Western and Japanese lung cancers have indicated substantial differences in the EGFR mutation frequency between these populations. To investigate the prevalence of EGFR in another distinct ethnic group, EGFR alterations were studied in 47 consecutive non small cell lung cancers from Saudi Arabia by immunohistochemistry, fluorescence in situ hybridization, and DNA sequencing.

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.

Colorectal carcinoma from Saudi Arabia. Analysis of MLH-1, MSH-2 and p53 genes by immunohistochemistry and tissue microarray analysis.

Objective: To document the incidence and role of p53 and DNA mismatch repair proteins in colorectal carcinomas, and to evaluate the relative frequency of major molecular pathways in colorectal cancers from Saudi Arabia.

Methods: We collected the formalin fixed, paraffin embedded tissues from 154 colorectal tumors (83 patients from King Faisal Specialist Hospital and Research Centre and 71 from Saudi Aramco Dhahran Health Centre) between January 1989 and December 2003. We analyzed the p53 and mismatch repair gene expression (hMSH-2, hMLH-1) by immunohistochemistry in tissue microarray format.