Immunohistochemical Expression of Cancer Stem Cell marker Aldehyde dehydrogenase 1B1 (ALDH1B1) in Colorectal Carcinoma

Document Type : Original Article

Authors

1 Departments of Pathology, Faculty of Medicine, Sohag University

2 Departments of Surgery, Faculty of Medicine, Sohag University

Abstract

Background: Colorectal cancer (CRC) is the third most common cause of cancer-related death in the US. One out of four patients presenting with conventionally staged node negative disease (AJCC Stage I and II), and over 50% of patients with Stage III disease will develop local recurrence and/ or metastases. Across all stages, approximately 30% of patients will develop distant metastases. Once metastases become clinically evident prognosis is often fatal. Biomarkers capable of predicting progression, risk stratification and therapeutic benefit are needed. CRCSC markers will identify a group of patients at high risk for progression. ALDH1 has been reported as a cancer stem cell marker in pancreatic, breast, prostate, and lung cancer, multiple myeloma and leukemia. By IHC analysis, human ALDH1B1 was found to be expressed at high levels in the small intestine, liver, and pancreas, and at lower levels in the lung and colon. This study aims to investigate ALDH1B1 expression in different types of colorectal carcinoma and correlate this expression with different clinicopathological parameters.
 Materials and Methods: ALDH1B1 immunostaining was studied in 50 specimens of colorectal carcinoma using avidin-biotin peroxidase method. Results: ALDH1B1 was strongly expressed in 12/50 (58%) of cases of colorectal carcinoma, moderately expressed in 31/50 (36%) of cases and weekly expressed in 7/50 (6%) of cases. ALDH1B1 expression in colorectal carcinoma was significantly positively correlated with tumor size (p= 0.021), tumor grade (p= 0.035) where the highest expression levels were associated with moderately or poorly differentiated tumors and positive regional lymph node status (p= 0.038).
Conclusion: The up-regulation of ALDH1B1 with increasing grade of colorectal carcinoma and presence of LN metastases indicates that ALDH1B1 might play a role in carcinogenesis and tumor progression. 

Keywords


  1. Deng SYang XLassus HLiang SKaur SYe QLi CWang LPRoby KFOrsulic SConnolly DCZhang YMontone KBützow RCoukos GZhang L. Distinct expression levels and patterns of stem cell marker, aldehyde dehydrogenase isoform 1 (ALDH1), in human epithelial cancers. PLoS One 2010; 5:10277.
  2. Fitzgerald TLRangan SDobbs LStarr SSigounas G,  J Surg Res. The impact of Aldehyde dehydrogenase 1 expression on prognosis for metastatic colon cancer. 2014; 192:82-89.
  3. Hamilton SR, Bosman FT, Boffetta P, Carneiro F, Hruban RH, Theise ND. Carcinoma of the colon and rectum. In: WHO Classification of Tumours of the Digestive System. Lyon: IARC Press 2010:134-146.
  4. Langan RCMullinax JERaiji MTUpham TSummers TStojadinovic AAvital I. Colorectal cancer biomarkers and the potential role of cancer stem cells. J Cancer. 2013; 4:241-250.
  5. Langan RCMullinax JERay SRaiji MTSchaub NXin HWKoizumi TSteinberg SMAnderson AWiegand GButcher DAnver MBilchik AJStojadinovic ARudloff UAvital I. A Pilot Study Assessing the Potential Role of non-CD133 Colorectal Cancer Stem Cells as Biomarkers. J Cancer. 2012; 3: 231-240.
  6. Lugli AIezzi GHostettler IMuraro MGMele VTornillo LCarafa VSpagnoli GTerracciano LZlobec I. Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EPCAM, and ALDH1 in colorectal cancer. Br J Cancer 2010; 103:382-390.
  7. Manfredi SBouvier AMLepage CHatem CDancourt VFaivre J. Incidence and patterns of recurrence after resection for cure of colonic cancer in a well defined population. Br J Surg 2006; 93:1115-1122.
  8. Siegel RWard EBrawley OJemal A. Cancer statistics: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011; 61:212-236.
  9. Stagos DChen YBrocker CDonald EJackson BCOrlicky DJThompson DCVasiliou V. Aldehyde dehydrogenase 1B1: molecular cloning and characterization of a novel mitochondrial acetaldehyde-metabolizing enzyme. Drug Metab Dispos. 2010; 38:1679-1687.
  10. Vasiliou V, Pappa A, Estey T. Role of human aldehyde dehydrogenases in endobiotic and xenobiotic metabolism. Drug Metab Rev. 2004; 36:279-299.
  11. Weisenberg E. TNM staging of colorectal carcinoma (AJCC 8th edition). PathologyOutlines.com. 2018; 25:1454-1458.
  12. Zlobec I, Gunthert U, Tornillo L, Iezzi G, Baumhoer D, Terracciano L, LuglI A. Systematic assessment of the prognostic impact of membranous CD44v6 protein expression in colorectal cancer. Histopathology. 2009; 55:564-575.