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).


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.


CONCLUSIONS
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.
Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway c.g.attramadal@odont.uio.no magnebr@odont.uio.no.
Cecilie Gjøvaag
CG
Attramadal
Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.
Sheeba
S
Kumar
Department of Otorhinolaryngology, Head and Neck Surgery, Oslo University Hospital, Rikshospitalet, Faculty of Medicine, University of Oslo, Oslo, Norway.
Morten E
ME
Boysen
Department of Pathology, Oslo University Hospital, Radiumhospitalet, Faculty of Medicine, University of Oslo, Oslo, Norway.
Hari Prasad
HP
Dhakal
Department of Pathology, Oslo University Hospital, Radiumhospitalet, Faculty of Medicine, University of Oslo, Oslo, Norway.
Jahn Marthin
JM
Nesland
Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway c.g.attramadal@odont.uio.no magnebr@odont.uio.no.
Magne
M
Bryne
D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002454:Cell Differentiation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D047368:Tumor Burden; D014746:Vimentin / Q000378:metabolism
D014408:Biomarkers, Tumor; D015820:Cadherins; D014746:Vimentin
CSC; EMT; Oral squamous cell carcinoma; prognosis; tumor budding