ABSTRACT
OBJECTIVE: LGR5 is pivotal to oral cavity development and is implicated in epithelial malignancy whereby stimulation of LGR5 potentiates canonical Wnt signaling. This investigation tested our hypothesis of a correlation between LGR5 expression and the severity of oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). STUDY DESIGN: Immunoreactive LGR5 protein expression was quantified in 342 tissue samples ranging in disease severity from normal through mild and moderate or severe OED to OSCC. RESULTS: LGR5 was restricted to the basal layers for normal tissues, projected to the stratum granulosum in severe dysplasia, intense in carcinoma nests of well-differentiated OSCC, but uniformly diffuse throughout poorly differentiated OSCC. Median LGR5 immunoreactivity index scores increased with disease severity: mild dysplasia = 1 < moderate or severe dysplasia = 2.5 < OSCC = 6. CONCLUSIONS: Inclusion of LGR5 in a panel of immunohistochemical biomarkers may improve identification of increased potential for malignancy in OED.
Subject(s)
Carcinoma, Squamous Cell/metabolism , Mouth Neoplasms/metabolism , Receptors, G-Protein-Coupled/metabolism , Biomarkers, Tumor/metabolism , Biopsy , Carcinoma, Squamous Cell/pathology , Epithelial Cells/metabolism , Epithelial Cells/pathology , Female , Humans , Immunohistochemistry , Male , Middle Aged , Mouth Neoplasms/pathology , Retrospective Studies , Severity of Illness IndexABSTRACT
Early diagnosis is vital for effective treatment of oral squamous cell carcinoma (OSCC). The optimal time for clinical intervention is prior to malignancy when patients present with oral potentially malignant lesions such as leukoplakia or erythroplakia. Transformation rates for oral dysplasia vary greatly and more rigorous methods are needed to predict the malignant potential of oral lesions. We hypothesized that the expression of two putative stem cell markers, ABCG2 and Bmi-1, would correlate with disease severity for non diseased, potentially malignant and OSCC specimens and cell lines derived from an equivalent range of tissues. We compared immunoreactive protein and relative gene expression of ABCG2 and Bmi-1 in eight cell lines derived from source tissues ranging in disease severity from normal (OKF6-TERT2) through mild and moderate/severe dysplasia (DOK, POE-9n) to OSCC (PE/CA-PJ15, SCC04, SCC25, SCC09, SCC15). We also analyzed immunoreactive protein expression of ABCG2 and Bmi-1 in 189 tissue samples with the same range of disease severity. A trend between oral lesion severity to ABCG2 and Bmi-1 immunostain intensity was observed. Flow cytometry of oral cell lines confirmed this trend and gave good correlation with RT-PCR results for ABCG2 (r = 0.919, P = 0.001; Pearson) but not Bmi-1 (r = -0.311). The results provide evidence of increased density of ABCG2 and Bmi-1-positive populations in malignant and oral potentially malignant lesions and derived cell lines, but that intragroup variability within IHC, flow cytometry, and RT-PCR results compromise the diagnostic potential of these techniques for discriminating oral dysplasia from normal tissue or OSCC.
Subject(s)
ATP-Binding Cassette Transporters/biosynthesis , Carcinoma, Squamous Cell/metabolism , Head and Neck Neoplasms/metabolism , Mouth Neoplasms/metabolism , Neoplasm Proteins/biosynthesis , Polycomb Repressive Complex 1/metabolism , ATP Binding Cassette Transporter, Subfamily G, Member 2 , ATP-Binding Cassette Transporters/genetics , ATP-Binding Cassette Transporters/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/biosynthesis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/genetics , Cell Line, Tumor , Female , Gene Expression , Head and Neck Neoplasms/genetics , Humans , Male , Middle Aged , Mouth Neoplasms/genetics , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Polycomb Repressive Complex 1/genetics , Squamous Cell Carcinoma of Head and Neck , Young AdultABSTRACT
Head and neck squamous cell carcinoma (HNSCC) is one of the world's top ten most common cancers. Current survival rates are poor with only 50% of patients expected to survive five years after diagnosis. The poor survival rate of HNSCC is partly attributable to the tendency for diagnosis at the late stage of the disease. One of the reasons for treatment failure is thought to be related to the presence of a subpopulation of cells within the tumour called cancer stem cells (CSCs). CSCs display stem cell-like characteristics that impart resistance to conventional treatment modalities and promote tumour initiation, progression, and metastasis. Specific markers for this population have been investigated in the hope of developing a deeper understanding of their role in the pathogenesis of HNSCC and elucidating novel therapeutic strategies.
