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HomeDiagnostic ImmunohistochemistryTissue Markers for Cancer Diagnostics

Tissue Markers for Cancer Diagnostics

Gabriela Gremel1, Julia Bergman Larsson1, Per-Henrik Edqvist1, Sanjay Navani2, Mathias Uhlén3, Fredrik Pontén1

1Uppsala University, Uppsala, Sweden, 2Lab Surgpath, Mumbai, India, 3Royal Institute of Technology, Stockholm, Sweden

Poster - The Human Protein Atlas

 

Background

Immunohistochemistry (IHC) represents an indispensable tool in cancer diagnostics. It adds information on protein expression on top of tissue morphology and can be used to verify or reject a tentative diagnosis. While most cancer patients present with malignancies that can be ascribed to a defined primary site, in 2-8% of all cases, no primary tumor can be detected despite exhaustive diagnostic examination. Since choice of therapy and prediction of survival in general are based on the primary tumor type, these patients represent a major diagnostic and therapeutic challenge.

Tissue Microarray Cohort

In a quest to identify novel, cancer type specific markers, a unique tissue microarray (TMA) cohort, containing material originating from 22 different primary tumor sites, was assembled (Table 1). To create a basis for all further analyses, the cohort was stained immunohistochemically for 24 well-established tumor markers (Figure 1 and Table 2).

PrimaryFemaleMaleAverage AgeMetastasisPrimaryRecurrenceTotal
Prostate-60672631360
Colrectal2337665010060
Breast591645010060
Stomach2139634713060
Lung4663-50590109
- Adenocarcinoma2835662931063
- Squamous cell1225641323037
- Lung NOS63642109
Ovary60-605010060
Endometrial60-671840260
Cervical60-552236260
Hepatocellular92164029130
Neroendocrine18126130 030
Sarcoma3525583226260
Urothelilal9116320 020
Renal cell carcinoma1129632020040
Lymphonama61464020020
Melanoma8126220 020
Testis-1932811019
Esophagus61665616022
Thyroid13535108018
Head and neck81258136120
Pancreas2733671941060
Cholangocarcinoma242063836044
Gall bladder53673508
Total5084326250242711940

Table 1. Summary of material included in the TMA cohort.

Results and Future Work

Representation of TMA cohort

Figure 1. Representation of TMA cohort. All cases were arrayed as duplicate cores onto 16 TMA slides and immunohistochemically stained according to a standard protocol. DAB (brown) was used as a chromogen and hematoxylin (blue) as counterstain. Exemplary IHC staining results for Prostate Specific Antigen (PSA) are shown.

True cell type specific markers are rare and most developed for hematopoietic tumors. For solid tumors, few specific markers exist, e.g. MelanA as a specific marker for melanoma (Table 2). For adenocarcinoma and squamous cell carcinoma such markers are exceedingly rare, mainly PSA (prostate cancer) and thyroglobulin (thyroid cancer) (Table 2). The application of marker panels or decision trees may increase the diagnostic accuracy. However, there remains an unmet need for identifying novel, better cancer markers.

IHC results from established diagnostic markers.

Table 2.Table IHC results from established diagnostic markers.

The Human Protein Atlas platform represents a unique resource for the identification of novel, cancer type-specific proteins1,2 (Figure 2). A thorough database search in combination with a strategy to mine publicly available and in-house generated transcriptome data has generated a list of candidate proteins, shortly to be analyzed on the presented TMA cohort.

Example of antibody staining data in a range of cancer types

Figure 2.Example of antibody staining data in a range of cancer types as found under www.proteinatlas.org.

References

1.
Uhlén et. al., Nat. Biotech., 2010;28(2). [Internet].
2.
Asplund A, Edqvist PD, Schwenk JM, Pontén F. 2012. Antibodies for profiling the human proteome-The Human Protein Atlas as a resource for cancer research. Proteomics. 12(13):2067-2077. https://doi.org/10.1002/pmic.201100504

The HPR project is funded by the Knut & Alice Wallenberg foundation. The atlas is part of the HUPO Human Antibody Initiative (HAI).

 

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