Oncology Biomarkers

Together with our research partners in the Human Protein Atlas project, we are in a unique position to perform antibody-based biomarker discovery. Learn about our oncology biomarkers T-PIT / TBX19, SATB2, PODXL, and  RBM3.  

T-PIT - a tool for classification of pituitary neuroendocrine tumors

Non-functioning pituitary neuroendocrine tumors (NF-PitNETs) is a heterogeneous group of hypophyseal neoplasms characterized by the lack of hormone hypersecretion. Absence of endocrine symptoms makes the diagnosis and adequate treatment of these tumors difficult. The use of pituitary-specific transcription factors has therefore been proposed for more precise classification of NF-PitNETs (Lloyd et al., 2017, Manojlovic-Gacic et al., 2018).

Three major transcription factors determining cell lineages are present in the adenohypophysis, including Pit-1 (POU1F1), SF-1 (NR5A1) and T-Pit (TBX19). Importantly, the expression of these transcription factors is preserved in both primary tumors and metastases.

T-Pit (TBX19) regulates development and differentiation of corticotroph ACTH- producing cells in the adenohypophysis (Lamolet et al., 2001). In a study on a patient cohort with different types of pituitary adenomas (Sjöstedt et al., 2017), distinct T-Pit immunoreactivity was demonstrated using the Anti-TBX19 antibody (HPA072686). T-Pit immunoreactivity was detected in the ACTH- expressing corticotroph cells in the normal pituitary and in all the corticotroph tumors, both silent and functioning. T-Pit expression was further detected in 8 of 15 tumors previously classified as null-cell adenomas, increasing the diagnostic accuracy.

IHC staining of ACTH-positive corticotrophic tumor
IHC staining of ACTH-positive corticotrophic tumor (Case 1, left) and gonadotrophic tumors (Case 2, middle and 3 left) using Anti-T-Pit / TBX19 monoclonal antibody (AMAb91409). Note the strong nuclear positivity in the majority of cells in corticotrophic tumor and absence of immunoreactivity in gonadotroph tumors. Insets in Case 2 and 3 images show nuclear positivity in normal adenohypophysis. Identical staining pattern is observed with both monoclonal and polyclonal antibody (see images below).
IHC staining of ACTH-positive corticotrophic tumor
IHC staining of ACTH-positive corticotrophic tumor (Case 1, left) and gonadotrophic tumors (Case 2, middle and 3 left) using Anti-T-Pit / TBX19 polyclonal antibody (HPA072686). Note the strong nuclear positivity in the majority of cells in corticotrophic tumor and absence of immunoreactivity in gonadotroph tumors. Insets in Case 2 and 3 images show nuclear positivity in normal adenohypophysis. Identical staining pattern is observed with both polyclonal antibody and monoclonal (see images above) antibody.

Monitoring of T-Pit allows for a more precise classification and better identification of NF-PitNETs and may contribute to adequate and timely treatment of patients.

Antibodies Targeting TBX19 / T-PIT

The antibodies listed below are of different clonality and target the same immunogen sequence.

Anti-TBX19 monoclonal antibody (AMAb91409)      

  • validated for IHC
  • isotype: mouse IgG1
  • sequence identity mouse/rat: 82%/32%

Anti-TBX19 polyclonal antibody (HPA072686)          

  • validated for IHC
  • isotype: rabbit IgG
  • sequence identity mouse/rat: 82%/32%

Product Citation

  • Sjöstedt E et al. A specific antibody to detect transcription factor T-Pit: a reliable marker of corticotroph cell differentiation and a tool to improve the classification of pituitary neuroendocrine tumors. Acta Neuropathol, 2017 Oct; 134(4):675- 677.

SATB2 – a diagnostic biomarker for tumors of colorectal origin

Cell- and cancer-type specific proteins are rare. The special AT-rich sequence-binding protein SATB2 has been identified as having a very selective expression pattern. In cells of epithelial lineages, SATB2 is expressed in glandular cells lining the lower gastrointestinal tract and expression is retained in a large majority of primary and metastatic colorectal cancers. Thus, SATB2 is a promising diagnostic biomarker for tumors of colorectal origin.

In a previously published study by Magnusson et al, it was shown, by analyzing more than 1800 tumor samples, that SATB2 expression is largely preserved in cells of colorectal cancer origin. More than 85% of all colorectal cancers showed distinct SATB2 immunostaining and when used in combination with Cytokeratin 20 analysis, SATB2 identified more than 95% of all tumors with a colorectal origin.

These promising data suggested that the combination of SATB2 and CK20 should be tested in an unbiased clinical study to further validate the initial findings. In a recent publication by Dragomir et al, the expression of SATB2 was analyzed in over 800 consecutive clinical cases for which CK20 immunostaining was considered necessary to obtain a final diagnosis. In this study, SATB2 showed 93% sensitivity and 77% specificity to determine a cancer of colorectal origin and in combination with CK7 and CK20, the specificity increased to 100%. SATB2 thus provides a new and advantageous supplement to current standards for clinical differential diagnosis.

 IHC staining using SATB2 Antibodies
Left: IHC staining of human colorectal cancer using SATB2 Antibody (AMAb90679) shows strong nuclear immunoreactivity in tumor cells. Middle: IHC analysis in human colon and esophagus tissues using Anti-SATB2 antibody (HPA029543). Right: IHC analysis in human rectum and liver tissues using SATB2 Antibody (AMAb90679) antibody. Corresponding SATB2 RNA-seq data are presented for the same tissues.

Antibodies targeting SATB2

The antibodies listed below are of different clonality and target the same immunogen sequence.

Anti-SATB2 monoclonal antibody (AMAb90679)

  • validated for IHC, WB
  • isotype: mouse IgG1
  • sequence identity mouse/rat: 100%/100%

Anti-SATB2 polyclonal antibody (HPA029543)          

  • validated for IHC, WB, ICC-IF
  • isotype: rabbit IgG
  • sequence identity mouse/rat: 100%/100%

Selected Product Citations

  • Magnusson K et al. SATB2 in combination with cytokeratin 20 identifies over 95% of all colorectal carcinomas. Am J Surg Pathol. 2011 Jul;35(7):937-48
  • Dragomir A et al. The role of SATB2 as a diagnostic marker for tumors of colorectal origin: results from a pathology-based clinical prospective study. Am J Clin Pathol. 2013 In Press. 

PODXL - an independent factor for poor prognosis and treatment stratification

Podocalyxin-like 1 (PODXL) is a cell-adhesion glycoprotein and stem cell marker that has been associated with aggressive tumor phenotype and adverse outcome in several cancer types.

In a number of published papers, Larsson et al have demonstrated that membraneous expression of PODXL is associated with unfavorable clinicopathological characteristics and independently predicts a poor prognosis in colorectal cancer (CRC). This has been demonstrated in three independent patient cohorts in total comprising more than 1000 patients. The results clearly demonstrate the potential utility of PODXL as a biomarker for more precise prognostication and treatment stratification in CRC. 

Boman et al have investigated the prognostic impact of membraneous PODXL expression in almost 500 cases of urothelial bladder cancer. They concluded that PODXL is indeed an independent risk factor for progressive disease and death in patients with urothelial bladder cancer and that this warrant further studies to fully evaluate the use of PODXL as a biomarker for improved treatment stratification of bladder cancer patients.

Orthogonal validation of PODXL antibodies.
Orthogonal validation of PODXL antibodies. Left: IHC analysis in human kidney and liver tissues using Anti-PODXL antibody (AMAb90667). Right: IHC analysis in human kidney and liver tissues using Anti-PODXL antibody (HPA002110). Corresponding PODXL RNA-seq data are presented for the same tissues.

Antibodies Targeting PODXL

The antibodies listed below are of different clonality and target the same immunogen sequence.

Anti-PODXL monoclonal antibody (AMAb90667)

  • validated for IHC, WB
  • isotype: mouse IgG1
  • sequence identity mouse/rat: 43%/41%

Anti-PODXL polyclonal antibody (HPA002110)​         

  • validated for IHC, WB, ICC-IF
  • isotype: rabbit IgG
  • sequence identity mouse/rat: 43%/41%

Selected Product Citations 

RBM3 - a prognostic and treatment predictive biomarker

The RNA-binding protein RBM3 has been identified via the Human Protein Atlas as an oncology biomarker through the differential expression pattern in several investigated cancers.

In general, the levels of RBM3 expression has been found to have a significant correlation to patient survival in breast, colon, ovarian, testicular, prostate and urothelial cancer as well as in malignant melanoma. The monoclonal anti-RBM3 antibody AMAb90655 has shown excellent specificity in Western blot analysis and is routinely used for staining of formalin-fixed paraffin-embedded tissues in IHC.

A major clinical challenge in urothelial cancer is the identification of high-risk patients among those diagnosed with non-invasive disease. Our data suggest that RBM3 expression analysis could be used as a prognostic factor for better stratification of patients, leading to more individualized treatment of patients with urothelial cancer. The prognostic significance of RBM3 in urothelial cancer has been confirmed in several independent cohorts.

These findings indicate that patient whose tumors express high levels of RBM3 could benefit from platinum-based treatment, whereas alternative treatments may be considered for patients having no or low RBM3 expression. In vitro cell-line experiments have also demonstrated the role of RBM3 in respect to treatment with platinum-based drugs like cisplatin. This has been further validated in a colorectal cancer cohort where patients with tumors expressing high levels of RBM3 showed a markedly increased survival upon platinum adjuvant treatment compared to patients receiving no- or non-platinum based adjuvant treatment.

Knockdown validation of Anti-RBM3 antibody (AMAb90655)
Knockdown validation. Left: ICC-IF staining of U-2 OS cells transfected with control siRNA using the anti-RBM3 antibody (AMAb90655), showing specific staining in the nucleoplasm in green. Middle: ICC-IF staining of U-2 OS cells transfected with siRNA probe 1 using the anti-RBM3 antibody (AMAb90655), showing remaining specific staining in the nucleoplasm in green.Right: ICC-IF staining of U-2 OS cells transfected with siRNA probe 2, using the anti-RBM3 antibody (AMAb90655), showing remaining specific staining in the nucleoplasm in green.

Antibodies targeting RBM3

The antibodies in the table below are of different clonality and target the same immunogen sequence.

Anti-RBM3 monoclonal antibody (AMAb90655)

  • validated for IHC, WB, ICC-IF
  • isotype: mouse IgG1
  • sequence identity mouse/rat: 94%/96%

Anti-RBM3 polyclonal antibody (HPA003624)​          

  • validated for IHC, WB, ICC-IF
  • isotype: rabbit IgG
  • sequence identity mouse/rat: 94%/96%

Biomarkers for licensing

Atlas Antibodies currently have several proprietary oncology biomarkers available for licensing. More information is available here