Expression of the Epidermal Growth Factor Seven-Transmembrane Member CD97 Correlates with Grading and Staging in Human Oral Squamous Cell Carcinomas

Abstract

Abstract Introduction: The oral squamous cell carcinoma (OSCC) is the sixth most common malignant tumor worldwide. No significant better progress has been made in the treatment of OSCCs during the last decades. The heterodimeric CD97 protein is a epidermal growth factor seven-transmembrane family member and was identified as a dedifferentiation marker in thyroid carcinomas. Nothing is known about CD97 in OSCCs. Material and Methods: Employing UV-laser microdissection, CD97 and its ligand CD55 were investigated in normal oral mucosa and OSCCs (n = 78) by multiplex reverse transcription-PCR. Frozen sections were investigated by immunohistochemistry. The effects of retinoic acid and sodium butyrate on the CD97/CD55 expression in OSCC cell lines were determined by quantitative PCR, immunocytochemistry, and flow cytometry. Results: Weak CD97 transcripts were expressed in normal mucosa and normal basal epithelial cells revealed specific CD97 immunostaining. Strong CD97 transcripts were detected in pT3/T4 and G3/G4 OSCC tissues, whereas pT1/T2 and G1/G2 carcinomas revealed weak CD97 transcript levels. A weak CD97 immunostaining was observed in pT1/T2 and G1/G2 tumors. By contrast, intensive CD97 immunostaining was detected in pT3/T4 OSCCs and G3/G4 lesions. CD55 gene expression was low in normal mucosa. All OSCCs, irrespective of stage and grading, displayed strong CD55 immunostaining. Sodium butyrate and retinoic acid inhibited CD97 mRNA and protein in OSCC cell lines. Interestingly, CD55 was up-regulated by both substances. Conclusion: We identified CD97 as a novel marker of dedifferentiated OSCC. Interaction of CD97 and CD55 may facilitate adhesion of OSCC cells to surrounding surfaces that would result in metastases and bad prognosis.