Abstract
Background
Colorectal cancer is a major cause of morbidity and mortality throughout the world. Although the diagnosis of colorectal cancer is straightforward in primary site, yet it may represent a diagnostic problem in metastatic tumor of unknown primary origin. Hence, immunohistochemical analysis in combination with morphologic assessment and correlation with clinical data becomes crucial, because it is important to specify the primary site of metastasis since some specific tumor types may respond well to targeted molecular therapies. Therefore, establishment of reliable diagnostic markers that confirm or rule out colorectal origin is mandatory.
Aim
To study the expression of cadherin 17 and CDX2 in colorectal carcinoma and to evaluate their diagnostic roles in identifying metastatic colonic from non-colonic adenocarcinomas in cancer of unknown primary site.
Design and Methods
This retrospective study included 65 cases of adenocarcinomas: 35 cases of colorectal adenocarcinoma (primary or metastatic) and 30 cases of non-colorectal adenocarcinoma. They were retrieved from the archives of Pathology Department of Ain Shams University and Ain Shams University Specialized Hospitals during the period from 2010 to 2015. Immunohistochemical study was performed using cadherin 17 and CDX2 antibodies.
Results
The sensitivity and specificity of CDX2 and cadherin 17 are 97.1% and 53.3% and 100% and 50% in detecting colonic adenocarcinoma respectively. The PPV, NPV, and overall accuracy of CDX2 versus cadherin 17 were 70.8%, 94.1%, and 76.9% versus 70%, 100%, and 76.9% respectively.
Conclusion
Cadherin 17 is a more sensitive marker than CDX2 in diagnosis of carcinoma of unknown primary site especially when colorectal carcinoma is suspected.
Similar content being viewed by others
Data Availability
All data generated or analyzed during this study are included in this published article.
Abbreviations
- CDH 17:
-
cadherin 17
- CDX2:
-
caudal-related homeobox gene 2
- CK 7:
-
cytokeratin 7
- CK20:
-
cytokeratin 20
- IHC:
-
immunohistochemistry
- PPV:
-
positive predictive value
- NPV:
-
negative predictive value
References
Gado A, Ebeid B, Abdelmohsen A, Axon A. Colorectal cancer in Egypt is commoner in young people: is this cause for alarm? Alexandria J Med. 2014;50:197–201. https://doi.org/10.1016/j.ajme.2013.03.003.
Metwally IH, Shetiwy M, Elalfy AF, Abouzid A, Saleh S, Hamdy M. Epidemiology and survival of colon cancer among Egyptians: a retrospective study. J Coloproctol (Rio J). 2018;38(1):24–9. https://doi.org/10.1016/j.jcol.2017.09.418.
Bayrak R, Haltas H, Yenidunya S. The value of CDX2 and cytokeratins 7 and 20 expression in differentiating colorectal adenocarcinomas from extraintestinal gastrointestinal adenocarcinomas: cytokeratin 7-/20+ phenotype is more specific than CDX2 antibody. Diagn Pathol. 2012;7(9):1–11. https://doi.org/10.1186/1746-1596-7-9.
Panarelli N, Yantiss R, Yeh M, Liu Y, Chen YT. Tissue-specific cadherin CDH17 is a useful marker of gastrointestinal adenocarcinomas with higher sensitivity than CDX2. Am J Clin Pathol. 2012;138:211–22. https://doi.org/10.1309/AJCPKSHXI3XEHW1J.
Su MC, Yuan RH, Lin CY, Jeng YM. Cadherin-17 is a useful diagnostic marker for adenocarcinomas of the digestive system. Mod Pathol. 2008;21:1379–86. https://doi.org/10.1038/modpathol.2008.107.
Chu PG, Weiss LM. Keratin expression in human tissues and neoplasms. Histopathology. 2002;40:403–39. https://doi.org/10.1046/j.1365-2559.2002.01387.x.
McGregor DK, Wu TT, Rashid A, Luthra R, Hamilton SR. Reduced expression of cytokeratin 20 in colorectal carcinomas with high levels of microsatellite instability. Am J Surg Pathol. 2004;28:712–8. https://doi.org/10.1097/01.pas.0000126757.58474.12.
Bayrak R, Yenidunya S, Haltas H. Cytokeratin 7 and cytokeratin 20 expression in colorectal adenocarcinomas. Pathol Res Pract. 2011;207(3):156–60. https://doi.org/10.1016/j.prp.2010.12.005.
Ordonez N. Cadherin 17 is a novel diagnostic marker for adenocarcinomas of the digestive System. Adv Anat Pathol. 2014;21(2):131–7. https://doi.org/10.1097/PAP.0000000000000008.
Altree-Tacha D, Tyrrell J, Haas T. CDH17 is a more sensitive marker for gastric adenocarcinoma than CK20 and CDX2. Arch Pathol Lab Med. 2017;141(3):150–7. https://doi.org/10.5858/arpa.2015-0404-OA.
Bosman FT, Carneiro F, Hruban RH, Theise ND. WHO classification tumours of the digestive system. 4th ed. IARC: Lyon; 2010.
Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG. WHO classification of tumours of the lung, pleura, thymus and heart. 7th ed. Lyon: International Agency for Research on Cancer; 2015.
Kurman RJ, Carcangiu ML, Herrington CS, Young RH. WHO classification of tumours of female reproductive organs. 4th ed. Lyon: IARC; 2014.
Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al. Meyer LR. AJCC cancer staging manual. 8th ed. Springer International Publishing: American Joint Commission on. Cancer. 2017.
Lin F, Shi J, Zhu S, Chen Z, Li A, Chen T, et al. Cadherin-17 and SATB2 are sensitive and specific immunomarkers for medullary carcinoma of the large intestine. Arch Pathol Lab Med. 2014;138(8):1015–26. https://doi.org/10.5858/arpa.2013-0452-OA.
Fizazi K, Greco FA, Pavlidis N, Pentheroudakis G. Cancers of unknown primary site: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2011;22(6):64–8. https://doi.org/10.1093/annonc/mdr389.
Pavlidis N, Khaled H, Gaafar R. A mini review on cancer of unknown primary site: a clinical puzzle for the oncologists. J Adv Res. 2015;6(3):375–82. https://doi.org/10.1016/j.jare.2014.11.007.
Taliano RJ, LeGolvan M, Resnick MB. Immunohistochemistry of colorectal carcinoma: current practice and evolving applications. Hum Pathol. 2013;44(2):151–63. https://doi.org/10.1016/j.humpath.2012.04.017.
Verzi MP, Shin H, Ho LL, Liu XS, Shivdasani RA. Essential and redundant functions of caudal family proteins in activating adult intestinal genes. Mol Cell Biol. 2011;31:2026–39. https://doi.org/10.1128/MCB.01250-10.
Olsen J, Espersen ML, Jess P, Kirkeby LT, Troelsen JT. The clinical perspectives of CDX2 expression in colorectal cancer: a qualitative systematic review. Surg Oncol. 2014;23:167–76. https://doi.org/10.1016/j.suronc.2014.07.003.
Shin JH, Bae JH, Lee A, Jung C-K, Yim HW, Park J-S, et al. CK7, CK20, CDX2 and MUC2 Immunohistochemical staining used to distinguish metastatic colorectal carcinoma involving ovary from primary ovarian mucinous adenocarcinoma. Jpn J Clin Oncol. 2010;40(3):208–13. https://doi.org/10.1093/jjco/hyp150.
Bian T, Jinli Zhao J, Jia Feng J, Qing Zhang Q, Qian L, Liu J, et al. Combination of cadherin-17 and SATB homeobox 2 serves as potential optimal makers for the differential diagnosis of pulmonary enteric adenocarcinoma and metastatic colorectal adenocarcinoma. Oncotarget. 2017;8(38):63442–52. https://doi.org/10.18632/oncotarget.18828.
Author information
Authors and Affiliations
Contributions
Mariam Bahaa conceived, designed, and coordinated the study; performed data collection; reviewed the histological diagnosis; evaluated immunohistochemistry; carried out photographing; and drafted the manuscript. Shadia Mabrouk conceived, designed, coordinated, and critically reviewed the study. Sahar Saad-ElDin coordinated and critically reviewed the study. Ola Nada coordinated and critically reviewed the study. Sarah Adel Hakim participated in the study design, reviewed the histological diagnosis, evaluated immunohistochemistry, performed the statistical analysis, helped in photographing, and contributed in writing the manuscript. The authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Ethics Approval and Consent to Participate
All patients who participated in this study signed a written, informed consent before surgery. The study was approved by the Research Ethical Committee (REC) at Faculty of Medicine, Ain Shams University (FWA 000017585).
Competing Interests
The authors declare that they have no competing interests.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Abouelkhair, M.B., Mabrouk, S.H., Zaki, S.S.A. et al. The Diagnostic Value of Cadherin 17 and CDX2 Expression as Immunohistochemical Markers in Colorectal Adenocarcinoma. J Gastrointest Canc 52, 960–969 (2021). https://doi.org/10.1007/s12029-020-00513-w
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12029-020-00513-w