Characterization of LGR5 expression in poorly differentiated colorectal carcinoma with mismatch repair protein deficiency

Abstract Background: Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a promising intestinal stem cell and carcinoma stem cell marker. We examined the relationship between mismatch repair (MMR) protein deficiency and LGR5 expression in poorly differentiated (PD) colorectal carcinoma (CRC). Methods: In 29 cases of PD-CRC, deficiencies in MMR proteins (MLH1, PMS2, MSH2, MSH6) and β-catenin expression were identified by immunohistochemistry (IHC). LGR5 expression was examined by the RNAscope assay in tissue microarrays. Results: LGR5 H-scores in MMR-deficient (MMR-D) cases were significantly lower than those in MMR-proficient (MMR-P) cases (P=0.0033). Nuclear β-catenin IHC scores in MMR-D cases were significantly lower than those in MMR-P cases (P=0.0024). In all cases, there was a positive correlation between LGR5 H-score and nuclear β-catenin IHC score (r=0.6796, P<0.001). Even in MMR-D and MMR-P cases, there was a positive correlation between LGR5 H-score and nuclear β-catenin IHC score (r=0.7180, P<0.0085 and r=0.6574, P<0.003, respectively). MMR-D CRC cases showed low expression of LGR5, which may be due to low activation of the Wnt/β-catenin signaling pathway. Conclusions: Our results reveal the relationship between LGR5 expression and MMR protein profiles in PD-CRC. A further study is warranted to confirm these findings.

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Characterization of LGR5 expression in poorly differentiated colorectal carcinoma with mismatch repair protein deficiency

10.21203/rs.2.23931/v1 ◽

2020 ◽

Author(s):

Tomoyuki Nakajima ◽

Takeshi Uehara ◽

Mai Iwaya ◽

Yukihiro Kobayashi ◽

Yasuhiro Maruyama ◽

...

Keyword(s):

Stem Cell ◽

Colorectal Carcinoma ◽

Mismatch Repair ◽

Tissue Microarrays ◽

Protein Deficiency ◽

Stem Cell Marker ◽

Positive Correlation ◽

Lgr5 Expression ◽

Poorly Differentiated ◽

The Relationship

Abstract Background Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a promising intestinal stem cell and carcinoma stem cell marker. We examined the relationship between mismatch repair (MMR) protein deficiency and LGR5 expression in poorly differentiated (PD) colorectal carcinoma (CRC). Methods In 29 cases of PD-CRC, deficiencies in MMR proteins (MLH1, PMS2, MSH2, MSH6) and β-catenin expression were identified by immunohistochemistry (IHC). LGR5 expression was examined by RNAscope assay in tissue microarrays. Results LGR5 H-scores in MMR-deficient (MMR-D) cases were significantly lower than those in MMR-proficient (MMR-P) cases ( P =0.0033). Nuclear β-catenin IHC scores in MMR-D cases were significantly lower than those in MMR-P cases ( P =0.0024). In all cases, there was a positive correlation between LGR5 H-score and nuclear β-catenin IHC score (r=0.6796, P <0.001). Even in MMR-D and MMR-P cases, there was positive correlation between LGR5 H-score and nuclear β-catenin IHC score (r=0.7180, P <0.0085 and r=0.6574, P <0.003, respectively). MMR-D CRC cases showed low expression of LGR5 , which might be due to low activation of the Wnt/β-catenin signaling pathway. Conclusion Our results reveal the relationship between LGR5 expression and MMR protein profiles in PD-CRC. A further study is warranted to confirm these findings.

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Characterization of LGR5 expression in poorly differentiated colorectal carcinoma with mismatch repair protein deficiency

BMC Cancer ◽

10.1186/s12885-020-06791-8 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Tomoyuki Nakajima ◽

Takeshi Uehara ◽

Mai Iwaya ◽

Yukihiro Kobayashi ◽

Yasuhiro Maruyama ◽

...

Keyword(s):

Colorectal Carcinoma ◽

Mismatch Repair ◽

Protein Deficiency ◽

Repair Protein ◽

Lgr5 Expression ◽

Poorly Differentiated ◽

Mismatch Repair Protein

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Evaluation of the role of CD44 as a cancer stem cell marker in colorectal carcinoma: immunohistochemical study

Menoufia Medical Journal ◽

10.4103/mmj.mmj_151_16 ◽

2017 ◽

Vol 30 (1) ◽

pp. 174 ◽

Cited By ~ 1

Author(s):

AyatG Lasheen ◽

NanisS Holah ◽

HayamA Aiad ◽

NancyY Asaad ◽

EnasA. B. Elkhouly

Keyword(s):

Stem Cell ◽

Colorectal Carcinoma ◽

Cancer Stem Cell ◽

Immunohistochemical Study ◽

Stem Cell Marker ◽

Cancer Stem Cell Marker ◽

Cell Marker

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

Gene ◽

10.1016/j.gene.2013.04.067 ◽

2013 ◽

Vol 525 (1) ◽

pp. 18-25 ◽

Cited By ~ 30

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

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

Pediatric and Developmental Pathology ◽

10.1177/1093526616686244 ◽

2017 ◽

Vol 20 (1) ◽

pp. 16-27 ◽

Cited By ~ 2

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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Clinicopathologic and prognostic significance of LGR5, a cancer stem cell marker in patients with colorectal cancer

Colorectal Cancer ◽

10.2217/crc-2019-0009 ◽

2019 ◽

Vol 8 (4) ◽

pp. CRC11 ◽

Cited By ~ 1

Author(s):

Chukwuemeka Ihemelandu ◽

Aisha Naeem ◽

Erika Parasido ◽

Deborah Berry ◽

Krysta Chaldekas ◽

...

Keyword(s):

Colorectal Cancer ◽

Stem Cell ◽

Cancer Stem Cell ◽

Prognostic Marker ◽

Prognostic Significance ◽

Stem Cell Marker ◽

Cancer Stem Cell Marker ◽

Cell Marker ◽

Independent Prognostic Marker ◽

Lgr5 Expression

Aim: To analyze the clinicopathologic and prognostic significance of Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), a cancer stem cell marker expression in a cohort of colorectal cancer patients (CRC). Patients & methods: A total of 76 formalin-fixed paraffin-embedded tissue blocks of primary or metastatic tumors from 49 CRC patients were collected for duration 2009–2015. LGR5 expression was assessed through immunohistochemical staining of a tissue microarray. Results: LGR5 was significantly over expressed in CRC tissue samples and found to be a statistically significant independent prognostic marker for an improved overall survival. Conclusion: LGR5 expression was higher in colorectal cancer than in normal tissue. LGR5 was an independent prognostic marker for better clinical outcomes and might be used as a potential therapeutic target in CRCs.

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377 Tis7 Deletion Inhibits Establishment and Growth of Crypt-Derived Intestinal Enteroids and Reduces Stem Cell Marker LGR5 Expression

Gastroenterology ◽

10.1016/s0016-5085(16)30402-4 ◽

2016 ◽

Vol 150 (4) ◽

pp. S85

Author(s):

Jianyun Lu ◽

Elzbieta A. Swietlicki ◽

Courtney Vishy ◽

Mackenzie Geisman ◽

Marc S. Levin ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Marker ◽

Cell Marker ◽

Lgr5 Expression

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LGR5 Expression is Associated with Prognosis in Poorly Differentiated Gastric Adenocarcinoma

10.21203/rs.3.rs-27693/v1 ◽

2020 ◽

Author(s):

Takehito Ehara ◽

Takeshi Uehara ◽

Tomoyuki Nakajima ◽

Yasuhiro Kinugawa ◽

Shota Kobayashi ◽

...

Keyword(s):

Gastric Adenocarcinoma ◽

Target Therapy ◽

Stem Cell Marker ◽

Rank Test ◽

Negative Group ◽

Positive Group ◽

Significant Difference ◽

Lgr5 Expression ◽

Poorly Differentiated

Abstract Background Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is an important cancer stem cell marker in gastric cancer. However, no detailed studies are available on LGR5 expression in poorly differentiated gastric adenocarcinoma (PD-AC). Therefore, we investigated the relationship between LGR5 expression and clinicopathological data in PD-AC.Methods LGR5 expression was identified in 41 PD-AC cases using RNAscope, which is a highly sensitive RNA in situ hybridization method. Epstein–Barr virus (EBV) infection was also detected by EBV in situ hybridization.Results In PD-AC, LGR5 expression was identified in 38 of 41 cases, and 17 cases were identified as LGR5 positive. The frequency of EBV positivity tended to be higher in the LGR5-negative group than in the LGR5-positive group (P = 0.0764). Furthermore, the frequency of vascular invasion tended to be higher in the LGR5-positive group than in the LGR5-negative group (P = 0.0764). A significant difference was found in overall survival (OS) between PD-AC cases in the LGR5-positive group and LGR5-negative group (log-rank test, P = 0.0108). The Cox proportional hazard regression model revealed that the LGR5-negative group (HR = 0.29; 95% CI: 0.11–0.74; P = 0.01) showed independently better OS for PD-AC.Conclusions The correlation between LGR5 positivity and poor prognosis in PD-AC may be applicable to target therapy for LGR5 and prognostic markers. Further study is warranted.

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