ABSTRACT
BACKGROUND: The purpose of this study was to investigate the expression of CD44 and/or CD133 immunophenotypes and the associated effects of matrix metalloproteinase-9 (MMP-9) in early-stage oral squamous cell carcinomas (SCC) to assess their influence on tumor prognosis. METHODS: The following data were derived from 150 patients: age, sex, primary anatomic site, smoking status, alcohol intake, recurrence, metastases, histological classification, treatment, disease-free survival (DFS), and overall survival (OS). Immunohistochemical study of CD44, CD133, and MMP-9 expression was performed on a tissue microarray of 150 paraffin blocks of oral SCCs. RESULTS: The predominant immunophenotype identified to exhibit a significant correlation with MMP-9 was the CD44+/CD133+. Multivariate analyses identified a significant correlation of OS with surgical treatment and with CD44+/CD133+ immunophenotype. CONCLUSION: This investigation demonstrated the prognostic importance of CD44/CD133 expression, which can help improve the prognostic value of surgical treatment for oral SCCs when diagnosed in early stages.
Subject(s)
Antigens, CD/metabolism , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/metabolism , Glycoproteins/metabolism , Hyaluronan Receptors/metabolism , Matrix Metalloproteinase 9/metabolism , Mouth Neoplasms/metabolism , Peptides/metabolism , AC133 Antigen , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/therapy , Cohort Studies , Female , Humans , Male , Middle Aged , Mouth Neoplasms/diagnosis , Mouth Neoplasms/therapy , Neoplasm Staging , Prognosis , Tissue Array AnalysisABSTRACT
BACKGROUND: Cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self-renewing CSC population that is also capable of differentiating into non-self-renewing cell populations that constitute the bulk of tumor. Stem cells renewal and differentiation can be directly influenced by the oxygen levels of determined tissues, probably by the reduction of oxidative DNA damage in hypoxic regions, thus leading to a friendlier microenvironment, regarding to clonal expansion and for resistance to chemotherapeutic regimens. Furthermore, there have been strong data indicating a pivotal role of hypoxic niche in cancer stem cells development. There are evidence that hypoxia could drive the maintenance of CSC, via HIF-1α expression, but it still to be determined whether hypoxia markers are expressed in breast tumors presenting CD44+CD24-/low immunophenotype. METHODS: Immunohistochemical analysis of CD44+CD24-/low expression and its relationship with hypoxia markers and clinical outcome were evaluated in 253 samples of breast ductal carcinomas. Double-immunolabeling was performed using EnVision Doublestain System (Dako, Carpinteria, CA, USA). Slides were then scanned into high-resolution images using Aperio ScanScope XT and then, visualized in the software Image Scope (Aperio, Vista, CA, USA). RESULTS: In univariate analysis, CD44+CD24-/low expression showed association with death due to breast cancer (p = 0.035). Breast tumors expressing CD44+CD24-/low immunophenotype showed relationship with HIF-1α (p = 0.039) and negativity for HER-2 (p = 0.013). CONCLUSION: Considering that there are strong evidences that the fraction of a tumour considered to be cancer stem cells is plastic depending upon microenvironmental signals, our findings provide further evidence that hypoxia might be related to the worse prognosis found in CD44+CD24-/low positive breast tumors.
Subject(s)
Biomarkers, Tumor/analysis , Breast Neoplasms/chemistry , CD24 Antigen/analysis , Carcinoma, Ductal, Breast/chemistry , Hyaluronan Receptors/analysis , Hypoxia-Inducible Factor 1, alpha Subunit/analysis , Neoplastic Stem Cells/chemistry , Brazil , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/mortality , Carcinoma, Ductal, Breast/pathology , Cell Hypoxia , Chi-Square Distribution , Female , Humans , Immunohistochemistry , Immunophenotyping/methods , Kaplan-Meier Estimate , Middle Aged , Neoplastic Stem Cells/pathology , Prognosis , Proportional Hazards Models , Receptor, ErbB-2/analysis , Risk Assessment , Risk Factors , Tissue Array AnalysisABSTRACT
BACKGROUND: The presence of cancer stem cell (CSC) antigens can be evidenced in some human tumors by phenotypic analysis through immunostaining. This study aims to identify a putative CSC immunophenotype in oral squamous cell carcinoma (OSCC) and determine its influence on prognosis. METHODS: The following data were retrieved from 157 patents: age, gender, primary anatomic site, smoking and alcohol intake, recurrence, metastases, histologic classification, treatment, disease-free survival (DFS), and overall survival (OS). An immunohistochemical study for CD44 and CD24 was performed in a tissue microarray of 157 paraffin blocks of OSCCs. RESULTS: In univariate analysis, the immunostaining pattern showed significant influences in relation to OS for alcohol intake and treatment, as well as for the CD44(+) and CD44(-) /CD24(-) immunophenotypes. The multivariate test confirmed these associations. CONCLUSIONS: Based on our results, the CD44 immunostaining and the absence of immunoexpression of these two investigated markers can be used in combination with other clinicopathologic information to improve the assessment of prognosis in OSCC.
