Preoperative assessment of CD44‐mediated depth of invasion as predictor of occult metastases in early oral squamous cell carcinoma

Abstract

Background Epithelial–mesenchymal transition and cancer stem‐like cells (CSC) have been linked to increased metastatic potential. We evaluated the prognostic impact of CD44, a CSC biomarker, on depth of invasion (DOI) and outcome in oral squamous cell carcinoma (OSCC). Methods Using a multivariable logistic regression model, we evaluated in early OSCCs the relationship between CD44 expression at the invasive tumor front, DOI, sentinel lymph node biopsy, extension of nodal involvement, and survival. We also assessed whether CT and/or MRI could predict DOI preoperatively. Results CD44 expression was associated with increased DOI (P = .018), worse disease‐specific survival (P = .041) but not with positive sentinel lymph node biopsy (P > .05). Each millimeter increase in DOI was associated with a 31.1% higher risk for positive sentinel lymph node biopsy (95% CI: 5.8%‐62.4%, P = .013) and with higher metastatic ratio (P = .015). Preoperative estimation of DOI by CT and/or MRI and histopathological DOI showed a strong correlation (P < .0001). Conclusions CD44 expression correlates with DOI, which predicts occult lymph node metastasis. Preoperative CT and/or MRI provides an accurate estimation of histopathological DOI. Both pieces of information gained preoperatively can help surgeons tailor their operation in regard to the surgical management of the neck.

Value of SUVmax for the Prediction of Bone Invasion in Oral Squamous Cell Carcinoma

“…Aggressive tumors undergo many genotypic and phenotypic changes through epithelial-mesenchymal transition (EMT) and cancer stem cells (CSC) enrichment to acquire invasive and metastatic properties [17]. Among others, these changes results in the expression of CD44, which allows cells to invade more deeply the surrounding tissue and enhances the glycolytic phenotype of cancer cells that are exposed to hypoxia [18]. The metabolic changes in hypoxic tumors induce tumor cells to increasingly metabolize glucose through glycolysis rather than the oxygen-dependent Krebs cycle (Warburg effect) [19].…”

A Complex and Evolutive Character: Two Face Aspects of ECM in Tumor Progression

“…High expression of CD44 in cancer cells is also associated with cancer stem cell (CSC) properties and is used as a CSC marker. CD44 + cancer cells show an increase in EMT and in invasion, correlated with poor prognosis ( 55 – 58 ).…”

Histometabolic Tumor Imaging of Hypoxia in Oral Cancer: Clinicopathological Correlation for Prediction of an Aggressive Phenotype

“…An automated Ventana BenchMark Ultra (Roche-Ventana Medical System, Tucson, AZ, United States) was used for staining according to the manufacturer's instructions. Immunohistochemical staining for CD44, for GLUT1, and for HIF1a were performed according to previous studies by our group (4,23). Positive and negative controls were included in all reactions.…”

“…CD44 and GLUT1 both showed a distinct membranous staining and were scored in a four-tiered system [negative, weak (1+), moderate (2+), and strong (3+) according to a previous publication (4)]. For GLUT1 (polyclonal antibody, 1:1,000, Millipore), staining of nearby erythrocytes was used as a positive control.…”

“…The importance of depth of invasion (DOI) of the primary tumor and its correlation with the prevalence of lymph node metastasis is now widely recognized. It was implemented into the latest edition of the tumor-node-metastasis (TNM) classification system (3,4).…”