HMGB1 Deficiency Occurs in a Broad Range of Human Cancers and Is Often Associated with Unfavorable Tumor Phenotype.

: Aberrant expression of high-mobility group protein B1 (HMGB1) has been linked to cancer development and progression. : To better comprehend the role of HMGB1 expression in cancer, a tissue microarray containing 14,966 samples from 134 different tumor entities and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. : Strong HMGB1 staining occurred in almost all normal cell types and in most cancers.

MTAP deficiency is highly homogeneous in advanced, muscle-invasive urothelial carcinoma of the urinary bladder.

Complete expression loss of S-methyl-5'-thioadenosine phosphorylase (MTAP) is caused by homozygous 9p21 deletion and results in a critical vulnerability of cancer cells towards drugs targeting multiple different pathways. MTAP deficiency is common in urothelial cancer, but data on its intratumoral heterogeneity-a potential obstacle for targeted therapies-are lacking. To study the heterogeneity of MTAP expression loss and 9p21 deletions in advanced primary urothelial cancers of the urinary bladder, a tissue microarray (TMA) composed of five different tissue spots from different tissue blocks of 105 pT2-4 urothelial carcinomas was analyzed by immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH).

High mobility group protein 2 (HMGA2) is highly expressed in a broad range of benign and malignant tumors.

High mobility group protein 2 (HMGA2) is an essential component of the enhanceosome that regulates gene transcription during organ development, and its re-expression in adult tissues is often linked to tumor formation and progression. To investigate HMGA2's role in cancer, a tissue microarray of 18,582 samples from 154 tumor types and 608 samples from 76 normal tissues was analyzed. HMGA2 expression was generally higher in cancer than in normal tissues.

Deficiency of MTAP Is Frequent and Mostly Homogeneous in Pancreatic Ductal Adenocarcinomas.

Background: The complete loss of S-methyl-5'-thioadenosine phosphorylase (MTAP) expression, often due to homozygous 9p21 deletion, creates a druggable vulnerability in cancer cells.

Methods: A total of 769 primary pancreatic ductal adenocarcinomas were analyzed on tissue microarrays with MTAP immunohistochemistry (IHC) and 9p21 fluorescence in situ hybridization (FISH). Intratumoral heterogeneity was assessed on a "heterogeneity" TMA containing up to nine samples from different areas of 236 primary tumor and nodal metastases, and whole sections of all tumor blocks from 19 cancers.

Reduced occludin expression is related to unfavorable tumor phenotype and poor prognosis in many different tumor types: A tissue microarray study on 16,870 tumors.

Occludin is a key component of tight junctions. Reduced occludin expression has been linked to cancer progression in individual tumor types, but a comprehensive and standardized analysis across human tumor types is lacking. To study the prevalence and clinical relevance of occludin expression in cancer, a tissue microarray containing 16,870 samples from 148 different tumor types and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry.

Estrogen receptor expression in human tumors: A tissue microarray study evaluating more than 18,000 tumors from 149 different entities.

Estrogen receptor (ER) is a ligand-activated transcription factor with a critical role in development and function of multiple organ systems and a well-established drug target for breast cancer. To comprehensively evaluate ER expression in normal and tumor tissues, a tissue microarray containing 18,560 samples from 149 different tumor types and subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry (IHC). ER positivity was found in 55 different tumor types including 26 entities with at least one strongly positive tumor.

Brachyury expression is highly specific for chordoma: A tissue microarray study involving 14,976 cancers from 135 different tumor types and subtypes.

Brachyury protein plays a role in defining the midline of bilaterian organisms. Commonly expressed in chordomas, brachyury immunohistochemistry is used to distinguish chordomas from their differential diagnoses. However, brachyury expression has also been described to frequently occur in other cancer entities.

Prevalence and clinical significance of Claudin-3 expression in cancer: a tissue microarray study on 14,966 tumor samples.

Background: Claudin-3 (CLDN3) participates in the formation of the tight-junctions (TJs) that regulate intercellular permeability. Altered CLDN3 expression has been linked to tumor progression in multiple tumor types. Despite its widespread expression in normal epithelial cells, CLDN3 is considered an attractive drug target candidate, since it may be more accessible in cancer cells than in normal cells due to their less orchestrated cell growth.

Cadherin-17 (CDH17) expression in human cancer: A tissue microarray study on 18,131 tumors.

Cadherin-17 (CDH17) is a membranous cell adhesion protein predominantly expressed in intestinal epithelial cells. CDH17 is therefore considered a possible diagnostic and therapeutic target. This study was to comprehensively determine the expression of CDH17 in cancer and to further assess the diagnostic utility of CDH17 immunohistochemistry (IHC).

Prostein expression in human tumors: a tissue microarray study on 19,202 tumors from 152 different Tumor entities.

Background: Prostein (P501S), also termed solute carrier family 45 member 3 (SLC45A3) is an androgen regulated protein which is preferentially expressed in prostate epithelial cells. Because of its frequent expression in prostate cancer, prostein was suggested a diagnostic prostate cancer marker.

Methods: In order to comprehensively assess the diagnostic utility of prostein immunohistochemistry, a tissue microarray containing 19,202 samples from 152 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry.

Epithelial splicing regulatory protein 1 and 2 (ESRP1 and ESRP2) upregulation predicts poor prognosis in prostate cancer.

Background: Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2) regulate alternative splicing events of various pre-mRNAs. Some of these targets play a role in cancer-associated processes, including cytoskeleton reorganization and DNA-repair processes. This study was undertaken to estimate the impact of ESRP1 and ESRP2 alterations on prostate cancer patient prognosis.

High expression of class III β-tubulin in upper gastrointestinal cancer types.

Class III β-tubulin (TUBB3) is a component of microtubules of neuronal cells that is upregulated in various cancer entities. To better understand the role of TUBB3 in upper gastrointestinal tract cancer types, the present study assessed TUBB3 expression in tissue microarrays including 189 gastric and 428 esophageal cancer. TUBB3 expression was detected in 62.

CAIX furthers tumour progression in the hypoxic tumour microenvironment of esophageal carcinoma and is a possible therapeutic target.

The hypoxic tumour microenvironment of solid tumours represents an important starting point for modulating progression and metastatic spread. Carbonic anhydrase IX (CAIX) is a known HIF-1α-dependent key player in maintaining cell pH conditions under hypoxia. We show that CAIX is strongly expressed in esophageal carcinoma tissues.

Influence of hypoxia-dependent factors on the progression of neuroblastoma.

Purpose: Several oxygen-dependent factors, e.g., CAIX (carbonic anhydrase IX) or phosphoglycerate kinase 1 (PGK1) interacting with the CXCR4/SDF1 axis (chemokine receptor 4/stromal cell derived factor 1) have been shown to be involved in processes of tumour pathology including tumourigenicity, tumour cell dissemination and poor survival in several solid tumour entities.

Carbonic anhydrase IX correlates with survival and is a potential therapeutic target for neuroblastoma.

Carbonic anhydrase IX (CAIX) is involved in pathological processes including tumorgenicity, metastases and poor survival in solid tumors. Twenty-two neuroblastoma samples of patients who were surgically treated at the University Medical Center Hamburg-Eppendorf were evaluated immunohistochemically for expression of CAIX. Results were correlated with clinical parameters and outcome.