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
• Tissue Microarray Cohort
• Results and Future Work
• References

 

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).

Primary	Female	Male	Average Age	Metastasis	Primary	Recurrence	Total
Prostate	-	60	67	26	31	3	60
Colrectal	23	37	66	50	10	0	60
Breast	59	1	64	50	10	0	60
Stomach	21	39	63	47	13	0	60
Lung	46	63	-	50	59	0	109
- Adenocarcinoma	28	35	66	29	31	0	63
- Squamous cell	12	25	64	13	23	0	37
- Lung NOS	6	3	64	2	1	0	9
Ovary	60	-	60	50	10	0	60
Endometrial	60	-	67	18	40	2	60
Cervical	60	-	55	22	36	2	60
Hepatocellular	9	21	64	0	29	1	30
Neroendocrine	18	12	61	30		0	30
Sarcoma	35	25	58	32	26	2	60
Urothelilal	9	11	63	20		0	20
Renal cell carcinoma	11	29	63	20	20	0	40
Lymphonama	6	14	64	0	20	0	20
Melanoma	8	12	62	20		0	20
Testis	-	19	32	8	11	0	19
Esophagus	6	16	65	6	16	0	22
Thyroid	13	5	35	10	8	0	18
Head and neck	8	12	58	13	6	1	20
Pancreas	27	33	67	19	41	0	60
Cholangocarcinoma	24	20	63	8	36	0	44
Gall bladder	5	3	67	3	5	0	8
Total	508	432	62	502	427	11	940

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

Results and Future Work

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.

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 proteins^1,2 (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.

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).