Journal of Gastrointestinal Cancer

, Volume 50, Issue 4, pp 824–837 | Cite as

The Prognostic Value of Cancer Stem Cell Markers (Notch1, ALDH1, and CD44) in Primary Colorectal Carcinoma

  • Salem Y. MohamedEmail author
  • Randa Mohamed Kaf
  • Mona Mostafa Ahmed
  • Amira Elwan
  • Hassan R Ashour
  • Amr Ibrahim
Original Research



Cancer stem cells proved to have a vital role in cell migration, invasion, metastasis, and treatment resistance of colorectal cancer (CRC) that subsequently lead to poor clinical outcomes. These stem cells may be a novel therapeutic target for the management of CRC progression. Signals of the Notch-1 pathway are responsible for acquisition of stem cell characters. ALDH1 and CD44 are usually detected in stem cells in colorectal cancer.


The aims of this work are to evaluate the immunohistochemical expression of cancer stem cell markers ALDH1, Notch1, and CD44 in colorectal cancer and investigate their correlation with clinicopathological characters and patient survival.


Paraffin-embedded specimens of 70 patients with primary colorectal carcinoma were analyzed for Notch 1, ALDH1, and CD44 expressions by immunohistochemistry.


Notch1 was mainly located in the cytoplasm of CRC tissues, rarely expressed in adjacent normal tissues. A highly statistically significant relationship was found between grading, lymphovascular invasion, the degree of lymphocytic infiltration, peritumoral budding, lymph node ratio, lymph node metastasis, and Notch1 expression (p < 0.001). There was a highly statistically significant relationship found between AJCC stage and Notch1 expression (p < 0.001). CD44 was mainly located in the cell membrane of CRC tissues. A highly statistically significant relationship was found between grading (p = 0.006), lymphovascular invasion, the degree of lymphocytic infiltration, peritumoral budding, lymph node metastasis, lymph node ratio, and CD44 expression (p < 0.001). There was a highly statistically significant relationship found between AJCC stage and CD44 expression (p < 0.001). ALDH1 was detected in the cytoplasm of the CRC tissue. A highly statistically significant relationship was found between grading, lymphovascular invasion, the degree of lymphocytic infiltration, peritumoral budding, lymph node metastasis, lymph node ratio, and ALDH1 expression (p < 0.001). There was a highly statistically significant relationship found between AJCC stage and ALDH1 expression (p < 0.001). There is a highly statistically significant direct correlation between Notch1, CD44 expression, and ALDH1 expression (p < 0.001).


There is a substantial correlation between Notch 1, ALDH1, and CD44 as cancer stem cell markers and lymph node metastasis, advanced stage and tumor recurrence in colorectal carcinoma.


Expression of stem cell markers ALDH1, Notch1, and CD44 correlates with poor prognosis in a CRC and represents an independent prognostic factor. They are associated with a feature of epithelial-mesenchymal transition evidenced by their association with high tumor burden.


Primary colorectal carcinoma Notch1 ALDH1 CD44 CSCs 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Gastroenterology and Hepatology Unit, Internal Medicine Department, Faculty of MedicineZagazig UniversityMarkaz El-ZakazikEgypt
  2. 2.Department of Pathology, Faculty of MedicineZagazig UniversityMarkaz El-ZakazikEgypt
  3. 3.Department of Clinical Oncology, Faculty of MedicineZagazig UniversityMarkaz El-ZakazikEgypt
  4. 4.Department of General Surgery, Faculty of MedicineZagazig UniversityMarkaz El-ZakazikEgypt

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