Tumor Budding, EMT and Cancer Stem Cells in T1-2/N0 Oral Squamous Cell Carcinomas.

BACKGROUND: Early oral carcinomas have a high recurrence rate despite surgery with clear margins. In an attempt to classify the risk of recurrence of oral squamous cell carcinomas, we explored the significance of tumor budding, epithelial-mesenchymal transition (EMT) and certain cancer stem cell markers (CSC). MATERIALS AND METHODS: Tumor budding (single cells or clusters of ≤5 cells in the tumor front, divided into high- and low-budding tumors), EMT and CSC markers were studied in 62 immunohistochemically stained slides of T1/2N0M0 oral squamous cell carcinomas. Tissues and records of follow-up were obtained from the Oslo University Hospital, Norway. Tumor budding, EMT and CSC markers were scored and analyzed. RESULTS: The only significant prognostic marker was tumor budding (p=0.043). Expression of the EMT marker E-cadherin was lost from the invasive front and tended to be a prognostic factor (p=0.17), and up-regulation of vimentin in tumor cells in the invasive front was found; this indicates that EMT had occurred. CSC markers were not associated with recurrence rate in the present study. CONCLUSION: A high budding index was related to poor prognosis in patients with oral cancer. Budding was associated with EMT-like changes. CSC factors were detected but reflected differentiation rather than stemness. Scoring of buds in patients with oral cancer may help discriminate invasive tumors prone to relapse, and thus, provide an indication for adjuvant therapy.

High nuclear SOX2 expression is associated with radiotherapy response in small (T1/T2) oral squamous cell carcinoma.

OBJECTIVE: Expression of the stem cell transcription factor SOX2 is often used to imply stemness and poor prognosis in cancer. However, its role in oral squamous cell carcinoma (OSCC) is not fully elucidated. MATERIAL AND METHODS: Tumour tissues from 62 patients with primary, node negative and non-metastatic OSCCs were used to evaluate SOX2 expression by immunohistochemistry. The results were correlated to clinicopathology, treatment and disease recurrences. RESULTS: The majority of the OSCCs (88%) expressed SOX2. Patients with higher nuclear SOX2 staining intensity in the invasive front compared to the adjacent normal epithelium, had a remarkable longer disease-free period if they received adjuvant post-operative radiotherapy (P = 0.001). This was in particular evident for highly differentiated OSCCs, as none of the high SOX2-expressing tumours reoccurred in contrast to all low SOX2-expressing OSCCs. CONCLUSIONS: High nuclear SOX2 expression in the invasive front was associated with dramatic longer disease-free period than low SOX2-expressing carcinomas after post-operative radiotherapy in small OSCCs. The result suggested that high nuclear SOX2 expression at the invasive front may predict radiosensitivity.

Radiological analysis of swallowing and functional outcomes after hypopharyngo-laryngectomy with reconstruction using a jejunal autograft.

CONCLUSION: We report a distinct pattern of tongue movement. This is interpreted as a compensatory mechanism after hypopharyngo-laryngectomy with reconstruction using a jejunal autograft. Passage through the oesophagus is mainly passive. OBJECTIVE: Swallowing is normally initiated voluntarily, and afterwards presumed to be controlled by brainstem reflexes. Resection of the hypopharynx with reconstruction may affect this control. This study attempted to perform a biomechanical analysis of the motility in the small bowel graft and suggest possible implications for surgical management. We also analysed how oesophageal passage is affected by surgery. METHODS: Five patients underwent a radiological examination of the neopharyngeal conduit and oesophagus and completed a simple questionnaire. RESULTS: The radiological examinations revealed a distinct pattern of tongue movement in all patients, resulting in varying degrees of thrust. Passage through the jejunal graft was mainly passive, but observations of progressive reduction in diameter of the graft indicated muscular tone that may preserve pressure generated by the lingual thrust. The oesophageal transport appeared to be rather passive and largely depended upon the effect of gravity. Two of five patients were unable to eat normal food. Their impaired swallowing resulted in severely reduced quality of life.