Yukihiro Hiraishi

Immunohistochemical expression of EGFR and p-EGFR in oral squamous cell carcinomas.

Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor of the ErbB family, which is expressed or highly expressed in a variety of solid tumors, including oral cancers. High EGFR expression has been correlated with tumor size, metastasis and survival. In recent years, EGFR has been considered a promising target for monoclonal antibody therapy. A total of 52 patients with oral squamous cell carcinoma (OSCC) were selected for EGFR and phosphorylated EGFR (p-EGFR) detection. Immunohistochemical staining was performed to evaluate EGFR and p-EGFR expression. Positive EGFR and p-EGFR staining was present in 92.3% (48/52) and 98.0% (51/52) of all cases, respectively. High EGFR and p-EGFR expression was present in 63.4% (33/52) and 69.2% (36/52) of all cases, respectively. EGFR and p-EGFR expression did not correlate with the clinical factors tumor stage, regional lymph node metastasis, or distant metastasis. However, a statistically significant correlation was identified between high EGFR expression and the pathologic factor tumor invasion. As a conclusion, the majority of OSCCs highly express EGFR and p-EGFR, indicating the importance of studying the efficacy of anticancer therapy targeting these signal factors.(Pathology Oncology Research Vol 12, No 2, 87–91)

EGFR inhibitor enhances cisplatin sensitivity of oral squamous cell carcinoma cell lines.

Epidermal growth factor receptor (EGFR) is involved in multiple aspects of cancer cell biology. EGFR has already been identified as an important target for cancer therapy, with various kinds of EGFR inhibitors currently used in treatment of several human cancers. Recently, EGFR and its downstream signaling pathways were identified as being associated with cisplatin sensitivity. In addition, EGFR inhibitors have shown significant promise for patients who failed cisplatin-based therapy. In this study, we investigated whether treatment with an EGFR inhibitor improves cisplatin sensitivity in oral squamous cell carcinoma (OSCC) cell lines. The effects of a combination of AG1478, a specific EGFR tyrosine kinase inhibitor, with cisplatin were evaluated in cultured OSCC cell lines and cisplatin-resistant sublines. Higher expression of EGFR and p-EGFR was found in the two cisplatin-resistant cell lines compared with the corresponding parental cell lines. In addition, augmented inhibition of OSCC cell growth by the combination of AG1478 with cisplatin was found in both cell lines. These results suggest that the combination of an EGFR inhibitor and cisplatin may be useful as a rational strategy for the treatment of patients with oral cancer with acquired cisplatin resistance.

Expression of lumican and fibromodulin following interleukin-1 beta stimulation of disc cells of the human temporomandibular joint.

Small leucine-rich repeat proteoglycans (SLRP) are present in the extracellular matrix of the temporomandibular joint (TMJ) disc. Lumican and fibromodulin, classified as class 2 SLRPs, play important roles in TMJ assembly, proliferation and inflammation. Degenerative change in the TMJ disc gives rise to the process of internal derangement (ID). In this study, we immunohistochemically examined the expression of lumican and fibromodulin in nine human TMJ specimens and examined the gene expression of both proteoglycans in cultured human TMJ disc cells under interleukin-1 beta (IL-1 β)-stimulated conditions. An articular disc cell line was established by collagenase treatment of a TMJ disc. The subcultured cells were then incubated for 1, 3, 6, 12, 24 or 48 h under both normal and IL-1 β (1 ng/mL) conditions. The gene expression of lumican and fibromodulin was examined using the reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR. We demonstrated that the expression of lumican significantly differs from that of fibromodulin in the deformed disc and that IL-1 β induces a significant increase in lumican mRNA, but not in fibromodulin mRNA, after 24∼48 h culture compared to cells cultured in the absence of IL-1 β (P<0.05). These results indicate that lumican and fibromodulin display different behaviors and that lumican may promote regeneration of the TMJ after degeneration and deformation induced by IL-1 β.

Expression of lumican related to CD34 and VEGF in the articular disc of the human temporomandibular joint.

Lumican belongs to the small leucine-rich repeat proteoglycan (SLRP) gene family and has been reported to exist in the cornea, intervertebral disc and tendon. Lumican plays a significant role in the assembly and regulation of collagen fibres. The human temporomandibular joint (TMJ) disc is made up of fibrocartilage with an extracellular matrix (ECM) composed of collagen and proteoglycans. The existence and behaviour of lumican have not been studied in the human TMJ disc. Therefore, we used immunohistochemical methods to detect lumican, CD34 and vascular endothelial growth factor (VEGF) and histochemical staining with toluidine blue in 13 human TMJ specimens (10 surgically removed and 3 obtained from autopsy). In both normal and deformed discs we observed staining with toluidine blue. We found that the area of metachromasia inside the deformed disc was uneven and expression of lumican was strong in the areas negative for metachromasia. Staining of VEGF and CD34 inside the deformed disc was seen. We confirmed the expression of lumican in the human TMJ disc and showed that a large number of fibroblast-like cells existed in the area of strong lumican expression. These new findings about the behaviour of lumican suggest that it may play a key role in the generation of a new collagen network by fibroblast-like cells.

Usefulness of Myofascial Flap Without Skin in Contemporary Oral and Maxillofacial Reconstruction

PURPOSE Pedicle myofascial graft should be considered in contemporary oral and maxillofacial reconstruction for the following reasons: 1) the pedicle myofascial unit is reliable and easily handled; 2) on the grafted myofascia in the oral cavity, the mucosa regenerates naturally with regard to suppleness and surface characteristics; and 3) vascularized myofascial coverage of tissues or materials is useful in some clinical situations. The purpose of this retrospective study was to evaluate the usefulness of this graft material. PATIENTS AND METHODS Using myofascial flaps from the pectoralis major muscle in 15 patients and from the platysma muscle in 11 patients, several types of reconstructive procedures were conducted in the Department of Oral and Maxillofacial Surgery, Wakayama Medical University. RESULTS Myofascial tissue was used to cover the surgical defect and for regeneration of oral mucosa (24 patients), to prevent exposure of the mandibular reconstruction plate (4 patients), for prevention of wound breakdown and secondary infection in the oral cavity (2 patients), for vascularized coverage of free grafted autologous bone (2 patients), and for protection of large vessels after radical neck dissection (9 patients). Although partial flap necrosis or wound dehiscence was noticed in 3 patients with a platysma-myofascial graft, the healing process of all patients was favorable and required no additional operations. This procedure is most suitable for the reconstruction of small to medium-sized soft tissue defects in the oral cavity, because it induces the formation of nearly normal mucosa through epithelial regeneration without clear scar formation. CONCLUSIONS Myofascial flap is a useful option in certain oral and maxillofacial reconstruction cases in which mucosal regeneration and/or vascularized soft tissue coverage are required.