Oncology Biomarkers - Assessing Cancer Development Oncology Biomarkers Need for Novel Cancer Biomarkers With a limited repertoire of protein biomar- Biomarkers for Licensing The microscopic evaluation of stained tis- ers available today there is a clear and un- Several proprietary oncology biomarkers sue sections from a tumor remains the met clinical need to identify novel sets of are available for licencing from Atlas Anti- gold standard for cancer diagnosis. How- biomarkers. The aim is to provide a more bodies, both Triple A Polyclonals and Pre- ever, in order to optimize patient treatment accurate diagnosis and a better assess- cisA Monoclonals. A selection of available and provide guidance for therapeutic in- ment of patient prognosis, ultimately lead- antibodies is presented below. tervention of the underlying disease there ing to a more individualized treatment. is often a need for additional tumor stratifi- Additional information on licensing of spe- cation methods. Atlas Antibodies recognize this need for cific biomarkers and information about At- new biomarkers. Together with our re- las Antibodies’ customized solutions and The analysis of protein expression in cells search partners in the Human Protein validation capabilities is available on re- from a tumor tissue often provides impor- Atlas project we are in a unique position quest by sending an email to: tant additional information to the patholo- to perform antibody-based biomarker dis- [email protected] or visit our gist. Immunohistochemistry (IHC) using covery. Research Collaborations page (atlasanti- protein specific antibodies provides a tool bodies.com/research/collaborations). to detect the presence, abundance and localization of specific proteins. T-PIT - A tool for classification of ACTH positive Gonadotrophic tumors, pituitary neuroendocrine tumors corticotrophic tumor normal pituitary as positive control Non-functioning pituitary neuroendo- crine tumors (NF-PitNETs) is a he- Case 1 Case 2 Case 3 terogeneous group of hypophyseal neoplasms characterized by the lack of hormone hypersecretion. Absence of endocrine symptoms makes the diag- nosis and adequate treatment of these tumors difficult. The use of pituitary-spe- cific transcription factors has therefore AMAb91409 been proposed for more precise classi- fication of NF-PitNETs2,3. Three major transcription factors de- termining cell lineages are present in the adenohypophysis, including Pit-1 (POU1F1), SF-1 (NR5A1) and T-Pit (TBX19). Importantly, expression of these transcription factors is preserved HPA072686 in both primary tumors and metastases. Immunohistochemical staining of ACTH-positive corticotrophic tumor (Case 1) and gonadotrophic tumors (Case 2 and 3) using Anti-T-Pit monoclonal (AMAb91409, upper panels) and polyclonal (HPA072686, lower T-Pit (TBX19) regulates develop- panels) antibodies. Note strong nuclear positivity in the majority of cells in corticotrophic tumor and absence ment and differentiation of corticotroph of immunoreactivity in gonadotroph tumors. Insets in Case 2 and 3 images show nuclear positivity in normal ACTH-producing cells in the adenohy- adenohypophysis. Identical staining pattern is observed with both monoclonal and polyclonal antibody. pophysis1. In a recent study on a patient Moreover, T-Pit expression was detect- References 1. Lamolet B et al. A pituitary cell-restricted T box factor, Tpit, cohort with different types of pituitary ed in 8 of 15 tumors previously classified activates POMC transcription in cooperation with Pitx home- adenomas4, distinct T-Pit immunoreac- as null-cell adenomas, thus increasing oproteins. Cell. 2001 Mar 23;104(6):849-59. tivity was demonstrated using the Anti- the diagnostic accuracy. 2. Lloyd SKW et al. Hearing optimisation in neurofibromatosis type 2: A systematic review. T-Pit antibody HPA072686. T-Pit im- Clin Otolaryngol. 2017 Dec;42(6):1329-1337 Monitoring of T-Pit thus allows for a munoreactivity was detected in the 3. Manojlovic-Gacic E et al. Histopathological classification of ACTH-expressing corticotroph cells in more precise classification and better non-functioning pituitary neuroendocrine tumors. Pituitary. 2018 Apr;21(2):119-129. the normal pituitary and in all the cor- identification of NF-PitNETs and may contribute to adequate and timely treat- 4. Sjöstedt E et al. A specific antibody to detect transcription ticotroph tumors, both silent and func- factor T-Pit: a reliable marker of corticotroph cell differentiation tioning. ment of patients. and a tool to improve the classification of pituitary neuroendo- crine tumours. Acta Neuropathol, 2017 Oct; 134(4):675-677. Page 2 (4) SATB2 – A diagnostic biomarker study to further validate the initial find- for tumors of colorectal origin ings. In a recent publication by Drago- Cell- and cancer-type specific proteins mir et al, the expression of SATB2 was are rare. The special AT-rich sequence- analyzed in over 800 consecutive clini- binding protein SATB2 has been iden- cal cases for which CK20 immunostain- tified as having a very selective ex- ing was considered necessary to obtain pression pattern. In cells of epithelial a final diagnosis. In this study, SATB2 lineages, SATB2 is expressed in glan- showed 93% sensitivity and 77% speci- dular cells lining the lower gastrointesti- ficity to determine a cancer of colorec- nal tract and expression is retained in a tal origin, and in combination with CK7 large majority of primary and metastatic and CK20, the specificity increased to colorectal cancers. Thus, SATB2 is a 100%. SATB2 thus provides a new and advantageous supplement to current promising diagnostic biomarker for tu- Immunohistochemical staining of human colorectal mors of colorectal origin. standards for clinical differential diag- tumor with Anti-SATB2 antibody (HPA029543) nosis. shows strong nuclear staining in tumor cells. In a previously published study by Mag- Related Publications Dragomir A et al. The role of SATB2 as a diagnostic mar- nusson et al. it was shown, by analyzing ker for tumors of colorectal origin: Results of a patholo- more than 1,800 tumor samples, that gy-based clinical prospective study. Am J Clin Pathol. 2014 May;141(5):630-8. SATB2 expression is largely preserved Elebro J et al. Prognostic and treatment predictive signifi- in cells of colorectal cancer origin. More cance of SATB1 and SATB2 expression in pancreatic and than 85% of all colorectal cancers showed periampullary adenocarcinoma. J Transl Med , 2014 Oct 17; 12:289. distinct SATB2 immunostaining and when Hedner C et al. SATB1 is an independent prognostic factor in used in combination with Cytokeratin 20 radically resected upper gastrointestinal tract adenocarcino- analysis, SATB2 identified more than ma. Virchows Arch , 2014 Dec; 465(6):649-659. 95% of all tumors with colorectal origin. Magnusson K et al. SATB2 in combination with cytokeratin 20 identifies over 95% of all colorectal carcinomas. Orthogonal validation: Am J Surg Pathol. 2011 Jul;35(7):937-48. These promising data suggested that Immunohistochemistry analysis in human rectum and liver tissues using AMAb90679 antibody. Cor- Nodin B et al. Molecular correlates and prognostic significan- the combination of SATB2 and CK20 responding SATB2 RNA-seq data are presented for ce of SATB1 expression in colorectal cancer. Diagn Pathol, 2012 Aug 30; 7:115. should be tested in an unbiased clinical the same tissues. PODXL - An independent factor death in patients with urothelial cancer for poor prognosis and treatment and that this warrant further studies to fully evaluate the use of PODXL as a stratification biomarker for improved treatment strati- Podocalyxin-like 1 (PODXL) is a cell- fication of bladder cancer patients. adhesion glycoprotein and stem cell marker that has been associated with aggressive tumor phenotype and ad- verse outcome in several cancer types. In a number of papers, Larsson et al. Orthogonal validation: have demonstrated that membraneous Immunohistochemistry analysis in human kidney expression of PODXL is associated with and liver tissues using AMAb90667 antibody. Corre- unfavourable clinicopathological char- sponding PODXL RNA-seq data are presented for the same tissues. acteristics and independently predicts a poor prognosis in colorectal cancer (CRC). This has been demonstrated in Related Publications Boman K et al. Podocalyxin-like and RNA-binding motif pro- three independent patient cohorts in to- tein 3 are prognostic biomarkers in urothelial bladder cancer: tal comprising more than 1,000 patients. a validatory study. Biomark Res , 2017 Mar 14; 5:10. Kaplan–Meier estimates of 5-year Overall Survival The results clearly demonstrate the po- (OS) according to PODXL expression in a urothelial Boman K et al. Membraneous expression of podocalyx- cancer patient cohort of 110 individuals. in-like protein is an independent factor of poor prognosis in tential utility of PODXL as a biomarker urothelial bladder cancer. Br J Cancer. 2013 Jun 11;108(11), for more precise prognostication and 2321-2328. treatment stratification in CRC. Borg D et al. Expression of podocalyxin-like protein is an independent prognostic biomarker in resected esophageal and gastric adenocarcinoma. BMC Clin Pathol , 2016 Jul Boman et al. have investigated the 29; 16:13. prognostic impact of membraneous Kusumoto H et al. Podocalyxin influences malignant potential by controlling epithelial–mesenchymal transition in lung ade- PODXL expression in almost 500 cases nocarcinoma Cancer Sci , 2017 Apr 3; 108(3):528-535. of urothelial cancer.