Cyclooxygenase-2 and c-erbB-2 Expression in Colorectal Carcinoma Assessed Using Tissue Microarrays

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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Cytoplasmic expression of HuR and cyclooxygenase-2 expression in colon cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e22161 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e22161-e22161

Author(s):

J. Song ◽

S. Choi ◽

J. Lee ◽

S. Lim

Keyword(s):

Colorectal Carcinoma ◽

Lymphatic Invasion ◽

Cyclooxygenase 2 ◽

Clinicopathological Parameters ◽

Cytoplasmic Expression ◽

Node Metastasis ◽

Embryonic Lethal ◽

Cox 2 ◽

Colorectal Cancer Patients ◽

Human Family

e22161 Background: HuR, human family embryonic-lethal abnormal vision-like protein, can bind to mRNAs and stabilizes them in the cytoplasm, resulting in more efficient translation. HuR is predominantly present in the nucleus and shuttles between the nucleus and cytoplasm. The mRNA of cyclooxygenase-2 (Cox-2) is stabilized by HuR in several cancers, including breast, stomach, lung and brain. Methods: We investigated the expression and its cellular location of HuR, and Cox-2 expression in 79 colorectal cancer patients with immunohistochemistry, and evaluated the biological implications in colorectal carcinoma. Results: Nuclear HuR expression was observed in 59 (74.7%) and cytoplasmic HuR expression was seen in 25 (31.6%). Cox-2 immunoreactivity was noted in 42 (53%). The expression of cytoplasmic HuR was significantly associated with Cox-2 expression (p=0.004). And cytoplasmic expression of HuR showed correlation with lymphatic invasion (p=0.025) and lymph node metastasis (p=0.027). Nuclear HuR showed no correlation with Cox-2 expression or other clinicopathological parameters examined. Conclusions: These results suggest that cytoplasmic translocation of HuR is associated with Cox-2 expression in some colorectal carcinoma. No significant financial relationships to disclose.

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