Human Protein Atlas

| October 24, 2007

The human protein atlas displays expression and localization of proteins in a large variety of normal human tissues and cancer cells. The data is publically available and presented as high resolution images of immunohistochemically stained tissues and cell lines. Available proteins can be reached through searches for specific genes or by browsing individual chromosomes.

The human protein atlas is periodically upgraded and new data is added to the database annually.

The Swedish Human Protein Atlas (HPA) program, funded by the Knut and Alice Wallenberg Foundation, has been set up to allow for a systematic exploration of the human proteome using Antibody-Based Proteomics. This is accomplished by combining high-throughput generation of affinity-purified (mono-specific) antibodies with protein profiling in a multitude of tissues/celltypes assembled in tissue microarrays. The program is run by Proteome Resource (HPR) Center located in Stockholm and Uppsala, Sweden.

The protein atlas contains histological images of sections from human tissues. The images represent a view similar to what is seen in a microscope when examining sections of tissue on glass slides. Each antibody in the database has been used for immunohistochemical staining of both normal and cancer tissue. The specific binding of an antibody to its corresponding antigen results in a brown-black staining. The tissue section is counterstained with hematoxylin to enable visualization of microscopical features. Hematoxylin staining is unspecific and results in a blue coloring of both cells and extracellular material.

Tissue microarrays provides the possibility to immunohistochemically stain a large number and variety of normal and cancer tissues. The used tissue microarrays include samples from 48 different normal tissue types and 20 different types of cancer. For each antibody, protein expression patterns in normal tissue can be viewed as triplicate samples and in cancer tissue as duplicate samples. Normal tissues are sampled from 144 (48 x 3) different individuals and cancer tissues are derived from 216 (216 x 2) unique tumors. Normally, a fraction (<5%) of the 576 images are missing for each antibody due to technical issues. Samples of normal and cancer tissue have been collected from anonymized paraffin embedded material of surgical specimens, in accordance with approval from the local ethics
committee.

Since specimens are derived from surgical material, normal is here defined as non-neoplastic and morphologically normal. It is not always possible to obtain fully normal tissues and thus several of the tissues denoted as normal will include alterations due to inflammation, degeneration and tissue remodeling. In rare tissues, hyperplasia or benign proliferations are included as exceptions. It should also be noted that within normal morphology there exists inter-individual differences and variations due to primary diseases, age, sex etc. Such differences may also effect protein expression and thereby immunohistochemical staining patterns.

Samples from cancer are also derived from surgical material. The inclusion of tumors has been based on availability and representativity. Due to subgroups and heterogeneity of tumors within each cancer type, included cases represent a typical mix of specimens from surgical pathology. However, an effort has been made to include high and low grade malignancies where such is applicable. In certain tumor groups, subtypes have been included, e.g. breast cancer includes both ductal and lobular cancer, lung cancer includes both squamous cell carcinoma and adenocarcinoma and liver cancer includes both hepatocellular and cholangiocellular carcinoma etc. Tumor heterogenity and inter-individual differences is also reflected in diverse expression of proteins resulting in variable immunohistochemical staining patterns.

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