scholarly journals Intestinal Stem Cell Marker, ASCL2 Is a Novel Prognostic Predictor in Esophageal Adenocarcinoma

2021 ◽  
Author(s):  
Yukiko Shibahara ◽  
Osvaldo Espin-Garcia ◽  
James Conner ◽  
Jessica Weiss ◽  
Mathieu Derouet ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Prognostic Factor ◽  
Esophageal Adenocarcinoma ◽  
Independent Prognostic Factor ◽  
Nodal Status ◽  
Stem Cell Marker ◽  
Intestinal Stem Cell ◽  
Cell Marker ◽  
Lgr5 Expression

Abstract Purpose: Stem cell markers play a significant role in esophageal adenocarcinoma carcinogenesis via Barrett’s esophagus; however, its utility as a prognostic biomarker has not been established. Methods: We analyzed the immunohistochemical expression of Ascl2 and Lgr5 utilizing whole slides (WS; 35 cases) and tissue microarray (TMA; 64 cases of esophageal adenocarcinoma with adjacent normal squamous epithelium, Barrett's esophagus, and dysplasia). Two pathologists semi-quantitatively scored stained slides independently/blindly, and the results were correlated with clinicopathologic factors and outcomes. Results: In WS, 51% and 57% expressed high Ascl2 and high Lgr5; in TMA, 69% and 88% expressed high Ascl2 and high Lgr5, respectively. In TMA, high Ascl2 and low Lgr5 expression significantly correlated to a higher number of involved lymph nodes (p=0.027 and p=0.0039), and Lgr5 expression significantly correlated to the pathological stage (p=0.0032). Kaplan-Meier analysis showed a negative impact of high Ascl2 expression on overall survival (OS; WS p=0.0168, TMA p=0.0276) as well as progression-free survival (PFS; WS p=0.000638, TMA p=0.0466), but not Lgr5. Multivariate Cox regression analysis revealed that Ascl2 expression is an independent prognostic factor for esophageal adenocarcinoma (OS; WS p=0.25, TMA p=0.011. PFS; WS p=0.012, TMA p=0.038). Analysis of the TCGA dataset showed that ASCL2 mRNA levels were correlated to nodal status but not overall survival.Conclusion: Intestinal stem cell marker, Ascl2 is an independent prognostic factor in esophageal adenocarcinoma. High Ascl2 levels were associated with nodal status in both immunohistochemical and mRNA expression. These findings may contribute to the development of prognosis-based subclassification of esophageal adenocarcinoma.

scholarly journals Intestinal Stem Cell Marker ASCL2 is a Novel Prognostic Predictor in Esophageal Adenocarcinoma

Cureus ◽  
2022 ◽  
Author(s):  
Yukiko Shibahara ◽  
Osvaldo Espin-Garcia ◽  
James Conner ◽  
Jessica Weiss ◽  
Mathieu Derouet ◽  
...  
Keyword(s):  
Stem Cell ◽  
Esophageal Adenocarcinoma ◽  
Stem Cell Marker ◽  
Intestinal Stem Cell ◽  
Cell Marker ◽  
Prognostic Predictor

267 INTESTINAL STEM CELL MARKERS AND ITS POTENTIAL USE IN THE CLINICOPATHOLOGICAL SETTING OF ESOPHAGEAL ADENOCARCINOMA

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Yukiko Shibahara ◽  
Osvaldo Espin-Garcia ◽  
James Conner ◽  
Jessica Weiss ◽  
Mathieu Derouet ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Lymph Nodes ◽  
Esophageal Adenocarcinoma ◽  
Negative Impact ◽  
Statistical Significance ◽  
Stem Cell Marker ◽  
Intestinal Stem Cell ◽  
Stem Cell Markers ◽  
Tcga Dataset

Abstract   Barrett’s esophagus (BE) is the primary precursor lesion of esophageal adenocarcinoma (EAC), which not only resembles the intestinal mucosa morphologically but also expresses various intestinal stem cell (ISC) markers. We hypothesized that ISC markers, Lgr5 (also a cancer stem cell marker), Ascl2 (fate determinator of ISC),Bmi1 (quiescent counterpart of Lgr5) and Cdx2 (primary regulator of ISC gene expression) have clinicopathological significance and could potentially be a predictor for survival in EAC. Methods Tissue microarray consisted of 64 EAC and 22 BE, and the expressions of Lgr5, Ascl2, Bmi1 and Cdx2 were analyzed using immunohistochemistry and scored independently by two pathologists. Clinicopathological factors (age, pathological grade and stage, affected lymph nodes, neoadjuvant therapy) were confounding factors, and univariable analysis using Fisher's exact tests as well as survival analysis using the Kaplan–Meier (KM) method and Cox proportional hazards regression (Cox PH) were performed to investigate its statistical significance. We performed a bioinformatic analysis of the TCGA dataset to validate the immunohistochemical findings. Results Among EAC, 69%, 88%, 64% and 70% expressed high Ascl2, Lgr5, Bmi1 and Cdx2, respectively. High Ascl2 and low Lgr5 expression significantly correlated to a higher number of involved lymph nodes; high Bmi1 expression significantly correlated to the pathological stage. Cdx2 was not correlated to any markers. KM analysis showed a negative impact of high Ascl2 expression on overall survival (OS; p = 0.0276) as well as progression-free survival (PFS; p = 0.0466), but not Lgr5, Bmi1 nor Cdx2. Cox PH analysis revealed Ascl2 (p = 0.011), and Cdx2 (p = 0.015) expression are independent prognostic factors for EAC. Conclusion Our results suggest that among the four ISC markers, Ascl2 and Cdx2 protein holds potential to be utilized as a prognostic biomarker. TCGA dataset revealed the association of ASCL2 mRNA expression with the number of positive lymph nodes but not overall survival, which implies further research is needed to explain the mechanism of Ascl2 overexpression in EAC carcinogenesis via ISC regulation.

scholarly journals Evaluation of the Adenocarcinoma-Associated Gene AGR2 and the Intestinal Stem Cell Marker LGR5 as Biomarkers in Colorectal Cancer

2012 ◽  
Vol 13 (4) ◽  
pp. 4367-4387 ◽  
Author(s):  
Manuel Valladares-Ayerbes ◽  
Moisés Blanco-Calvo ◽  
Margarita Reboredo ◽  
María J. Lorenzo-Patiño ◽  
Pilar Iglesias-Díaz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cell ◽  
Stem Cell Marker ◽  
Intestinal Stem Cell ◽  
Cell Marker

Expression of the putative stem cell marker Musashi-1 in Barrett's esophagus and esophageal adenocarcinoma

2010 ◽  
Vol 23 (7) ◽  
pp. 580-589 ◽  
Author(s):  
Y. V. Bobryshev ◽  
A. K. Freeman ◽  
N. K. Botelho ◽  
D. Tran ◽  
A. J. M. Levert-Mignon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Barrett’S Esophagus ◽  
Esophageal Adenocarcinoma ◽  
Barrett's Esophagus ◽  
Stem Cell Marker ◽  
Cell Marker ◽  
Putative Stem Cell

Lgr5 expression as stem cell marker in human gastric gland and its relatedness with other putative cancer stem cell markers

Gene ◽  
2013 ◽  
Vol 525 (1) ◽  
pp. 18-25 ◽  
Author(s):  
Chen Wu ◽  
Yuanyuan Xie ◽  
Feng Gao ◽  
Yanan Wang ◽  
Yawei Guo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cancer Stem Cell ◽  
Gastric Gland ◽  
Stem Cell Marker ◽  
Stem Cell Markers ◽  
Cell Marker ◽  
Cell Markers ◽  
Cancer Stem Cell Markers ◽  
Lgr5 Expression

scholarly journals Immunohistochemical Analysis of the Stem Cell Marker LGR5 in Pediatric Liver Disease

2017 ◽  
Vol 20 (1) ◽  
pp. 16-27 ◽  
Author(s):  
Zahida Khan ◽  
Anne Orr ◽  
George K Michalopoulos ◽  
Sarangarajan Ranganathan
Keyword(s):  
Stem Cell ◽  
Liver Disease ◽  
Liver Diseases ◽  
Chronic Liver ◽  
Stem Cell Marker ◽  
Cell Marker ◽  
Regenerative Response ◽  
Hepatocyte Regeneration ◽  
Pediatric Liver ◽  
Lgr5 Expression

Aims In regenerating liver, hepatic progenitor cells (HPCs) are recruited in response to injury; however, few highly specific human HPC markers exist for the hepatocyte lineage. Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), a Wnt-associated stem cell marker, has been extensively studied in intestinal stem cells, but little is known about its expression in human liver. We hypothesized that LGR5+ HPCs are induced in the regenerative response to pediatric liver injury. Methods and results Immunohistochemistry was used to characterize LGR5 expression in pediatric liver explants (n = 36). We found cytoplasmic LGR5 expression in all cases; although, much less was observed in acute hepatic necrosis compared to chronic liver diseases. In the latter cases, >50% of hepatocytes were LGR5+, signifying a robust regenerative response mainly in the periphery of regenerative nodules. Only weak LGR5 staining was noted in bile ducts, suggesting hepatocyte-specific expression at the interface. Conclusions Although we observed some degree of regenerative response in all cases, LGR5 was highly expressed in chronic liver disease, possibly due to alternate regeneration and reprogramming pathways. LGR5 is predominant in peri-septal hepatocytes rather than epithelial cell adhesion molecule (EpCAM) positive ductular reactions in chronic pediatric liver diseases and may represent a transitional HPC phenotype for the hepatocyte lineage. These studies are the first to support a unique role for LGR5 in human hepatocyte regeneration and as a potential predictive biomarker for recovery of liver function in children. Future work will also investigate the molecular mechanisms behind LGR5 expression.

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