Cancer stem cells: mediators of tumorigenesis and metastasis in head and neck squamous cell carcinoma.

BACKGROUND: Cancer stem cells (CSCs) represent a subpopulation of cells responsible for tumor growth. Their role in head and neck squamous cell carcinoma (HNSCC) tumorigenesis and metastasis remains uncertain. METHODS: Wound healing and an orthotopic animal model were used to study cells expressing the CSC phenotype (CD44(high) and aldehyde dehydrogenase [ALDH](+)) and assess mobility, tumorigenesis, and metastasis. A prospective collection of 40 patient-derived primary HNSCC specimens were analyzed for CSC-proportion compared to clinical variables. RESULTS: CSCs exhibited significantly faster wound closure and greater tumorigenesis and regional metastasis in vivo than non-CSCs. In primary patient tumors, size and advanced stage were correlated with elevated proportion of CSCs, however, not with survival. CONCLUSION: HNSCC stem cells mediate tumorigenesis and regional metastasis in vivo. In primary patient tumors, CSC-proportion was associated with tumor size and stage, but not with metastatic spread or survival. CSC burden alone may only represent a minor variable in understanding CSCs and metastasis.

Head and neck squamous cell carcinoma in pregnant women.

BACKGROUND: The aim of this study was to investigate oral cancer in pregnant women, a rare but therapeutically challenging patient subset. METHODS: After institutional review board approval, an EMERSE search was used to identify all women treated at the University of Michigan from 1998 to 2010 with head and neck squamous cell carcinoma (HNSCC) during pregnancy. This identified 4 patients with tongue cancer. Biomarkers and human papillomavirus (HPV) were assessed by immunohistochemistry and multiplex PCR/mass spectrometry, respectively. RESULTS: Two patients responded well to therapy and are alive more than 10 years after diagnosis; 2 patients died of disease. All tumors overexpressed EGFR and Bcl-xL, 3 of 4 overexpressed c-Met, both tumors that progressed overexpressed p53. All tumors were negative for HPV, p16, estrogen receptor, progesterone receptor, and HER-2. CONCLUSIONS: Biomarkers of aggressive tumors (high EGFR, c-Met; high Bcl-xL-low p53) did not correlate with outcome. Additional studies are needed to determine whether perineural invasion, delay in diagnosis, and p53 overexpression are factors in poor survival.

Survivin gene-expression and splicing isoforms in oral squamous cell carcinoma.

PURPOSE: Survivin, an inhibitor of apoptosis protein and a cell cycle regulator, has been detected in the majority of human cancers. Five splice variants (survivin, survivin-2alpha, survivin-2B, survivin-3B, and survivin-DeltaEx3) have been identified; their expressions have been investigated here. METHODS: By means of RT real-time PCR and immunohistochemistry, we have evaluated survivin isoform expressions at both mRNA and protein levels in human normal oral tissue, precancerous lesions, and oral squamous cell carcinoma (OSCC). Their correlations with the pathological findings have also been analyzed. RESULTS: Expression levels of all survivin transcript variants were markedly elevated in OSCC when compared to normal tissues. One-way analysis of variance (ANOVA) revealed highly significant up-regulation of survivin (P = 0.001), survivin-DeltaEx3 (P = 0.001) and survivin-2B (P = 0.004), whereas survivin-3B showed a minor increase in OSCC compared to normal mucosa. CONCLUSIONS: Our findings suggest that survivin isoforms deregulation may have significant implications in tumor aggressiveness and prognosis.