Xinming Chen

Expression of EphA2 and VEGF in squamous cell carcinoma of the tongue: Correlation with the angiogenesis and clinical outcome

Eph-ephrin binding has been linked to tumor biology and VEGF has been reported to participate in the tumor angiogenesis regulated by Eph-ephrin. The present study was designed to evaluate the expression of EphA2 and VEGF in relation to angiogenesis and clinical outcome in squamous cell carcinoma of oral tongue. Immunohistochemical staining was used to determine the protein expression levels of EphA2 and VEGF in 59 surgically resected tongue carcinomas and 10 tumor-free mucosas. In all cases, microvessel density (MVD) was evaluated by counting CD34-reactive endothelial cells or endothelial cell clusters. Both EphA2 and VEGF staining activities in squamous cell carcinoma of oral tongue were more significant than those in normal mucosa (P<0.01). MVD had significant correlations with EphA2 and VEGF expression (P<0.01). The EphA2, VEGF, and MVD were significantly correlated with tumor size, clinical stage, lymph invasion, recurrence, and distant metastasis (P<0.05). Multivariate analysis showed EphA2, VEGF expression, MVD, and clinical stage had an independent prognostic effect on overall survival. We conclude that the overexpression of EphA2 and VEGF are related to malignancy in squamous cell carcinoma of oral tongue. Clinical outcomes raised the possibility that the overexpression of those proteins might contribute to tumor angiogenesis and have prognostic value in tongue cancer.

The expression of NF-κB, Ki-67 and MMP-9 in CCOT, DGCT and GCOC

Calcifying odontogenic cysts (COCs) represent a group of rare odontogenic lesions with a diversity of clinicopathological and behavioral features. According to the WHO classification of head and neck tumors in 2005, COC has been divided into calcifying cystic odontogenic tumor (CCOT), dentinogenic ghost cell tumor (DGCT) and ghost cell odontogenic carcinoma (GCOC). With few reports available on its immunohistochemical profile, this study investigated the histopathological features and the expression of nuclear factor kappaB (NF-kappaB), Ki-67 and matrix metalloproteinase-9 (MMP-9) in CCOT, DGCT and GCOC. According to the WHO classification of head and neck tumors in 2005, 26 cases of the so-called COC were diagnosed as CCOT (n=14), DGCT (n=7) and GCOC (n=5), respectively. The specimens of 26 COCs and 10 classic ameloblastomas (as control group) were examined by immunohistochemistry using anti-NF-kappaB p65, anti-Ki-67 and anti-MMP-9 antibodies and by in situ hybridization(ISH)using anti-MMP-9 mRNA probes. Immunohistochemical reactivity for NF-kappaB was mainly detected in the cytoplasm of tumor cells, and nuclear reactivity was only seen in few tumor cells in COC and classic ameloblastomas. Rate of nuclear staining was less than 1%. The expression of Ki-67 in GCOC was significantly higher than those in CCOT (p<0.001), DGCT and ameloblastoma (p<0.005). In COCs and ameloblastomas, expression of MMP-9 mRNA and protein was detected in tumor cells as well as in stromal cells. The positive staining for MMP-9 protein was detected in stromal cells of all GCOC cases and was significantly stronger than those in CCOT and DGCT groups (p<0.05). NF-kappaB may minimally affect the progression and local invasiveness of CCOT, DGCT and GCOC. GCOC show significantly higher proliferative activity than CCOT and DGCT. MMP-9 in stroma is associated with invasive ability of the CCOT, DGCT and GCOC.

Expression of Caveolin-1 in Mucoepidermoid Carcinoma of the Salivary Glands: Correlation With Vascular Endothelial Growth Factor, Microvessel Density, and Clinical Outcome

Caveolin‐1, which has been proposed as a candidate tumor suppressor, plays a regulatory role in several signaling pathways. The importance of caveolin‐1 in endothelial cells in angiogenesis has been confirmed. The clinicopathologic significance of caveolin‐1 expression and its correlation with angiogenesis remains unknown in mucoepidermoid carcinoma (MEC) of the salivary glands.

Benign Fibro-Osseous Lesions of the Jaws: A Study of 127 Chinese Patients and Review of the Literature

The aim of this study is to analyze all the cases of benign fibro-osseous lesions treated at School and Hospital of Stomatology, Wuhan University, to compare the results obtained in this study with those previously documented by other authors. The 127 cases diagnosed as a fibro-osseous lesion were retrieved, and information about these lesions was documented. In all, 127 cases of benign fibro-osseous lesions were surgically treated. Of these, 55 were cemento-ossifying fibroma, 43 ossifying fibroma, and 29 fibrous dysplasia. Cemento-ossifying fibromas mostly occur in men of the second decades, mostly in the mandible. Ossifying fibromas had almost equal sex predilection and age distribution peaked in the second decades, mostly in the mandible. Fibrous dysplasia also had equal sex predilection, and age distribution peaked in the second and third decades, with equal occurrence in both jaws. The tumors needed to have a regular follow-up after the surgery.

Slug is a key mediator of hypoxia induced cadherin switch in HNSCC: correlations with poor prognosis.

OBJECTIVES According to recent studies, the function of Slug in hypoxia induced cadherin switch differs from cancer to cancer. Whether Slug is an essential mediator of the tumor hypoxia induced cadherin switch in head and neck squamous cell carcinoma (HNSCC) and the prognostic role of Slug in HNSCC patients are not elucidated. The aim of this study is to investigate the role of the Slug in cadherin switch induced by hypoxia in HNSCC. MATERIALS AND METHODS Two HNSCC cell lines and 119 HNSCC specimens were selected for the present experiments. E/N-cadherins expression and tumor cell invasion responding to hypoxia/HIF-1α overexpression and the silence of Slug/SnaI2 gene were detected in vitro. HNSCC specimens were analyzed by immunohistochemistry staining to correlate the expressions of Slug, HIF-1α and E/N-cadherins with clinical outcomes. RESULTS AND CONCLUSION Our research evidenced that Slug was extremely elevated in the HNSCC cells in response to hypoxia/HIF-1α overexpression. Suppressing Slug expression impaired HIF-1α induced cadherin switch and tumor invasion. In HNSCC tissues, relatively high expression of Slug was detected to be associated with endogenous HIF-1α overexpression, cadherin switch, the risk of lymph node metastasis, and a more advanced TNM stage. Additionally, aberrant Slug expression combined with HIF-1α overexpression and cadherin switch was significantly correlated with shorter HNSCC patient survival. In conclusion, Slug is necessary for hypoxia-induced cadherin switch in HNSCC and may be used as a potential risk marker in predicting HNSCC clinical outcomes.

Association of increased ligand cyclophilin A and receptor CD147 with hypoxia, angiogenesis, metastasis and prognosis of tongue squamous cell carcinoma.

Huang C, Sun Z, Sun Y, Chen X, Zhu X, Fan C, Liu B, Zhao Y & Zhang W 
(2012) Histopathology 60, 793–803

Myoepithelial carcinoma of intraoral minor salivary glands: a clinicopathological study of 7 cases and review of the literature

OBJECTIVE Myoepithelial carcinoma (MC), also known as malignant myoepithelioma, is a rare malignant salivary gland neoplasm with a predilection for the parotid gland. We present the clinicopathological and immunohistochemical features of 7 cases of intraoral MC in attempt to better understanding this entity. STUDY DESIGN Seven intraoral MCs were retrieved from the files of the Department of Oral Pathology, School of Stomatology, Wuhan University, during a 10-year period. Immunohistochemical markers, including cytokeratin (CK) AE1/AE3, S100, vimentin, smooth muscle actin (SMA), p63, and maspin, were used to further characterize these lesions. A review of contemporary relevant literature is also provided. RESULTS The patients were 5 women and 2 men, and the age range was 37 to 75 years (mean 57.9 years). Three cases arose in the hard palate, 2 in the retromolar region, and 1 each in the tongue and the floor of the mouth. Histologically, the tumors exhibited a solid architecture with cells arranged in nodules, nests, trabeculae, or cords. The epithelioid cell type is the most frequently encountered, followed by clear cells. The tumor-associated matrix is more prevalent hyalinized than myxoid. Immunohistochemically, CK AE1/AE3, S100, vimentin, p63, and maspin were expressed in all cases. Positivity for SMA was seen in 3 tumors. Five patients with follow-up information showed no evidence of disease after a mean follow-up of 69.6 months (range 22-108 months). CONCLUSIONS Combining the current series with 21 additional cases in the literature indicated that myoepithelial carcinoma of intraoral minor salivary glands is generally a low-grade malignant tumor with little propensity for regional or distant metastasis and low recurrence. Awareness of the clinicopathological and immunohistochemical features of intraoral MC is necessary for accurate diagnosis. Wide local excision with tumor-free margins is the treatment of choice.

Expression of allograft inflammatory factor‐1 and CD68 in haemangioma: implication in the progression of haemangioma

Background  Recent studies revealed that immune and immune‐mediated inflammatory events may contribute to the pathogenesis of haemangioma. As a modulator of immune responses, the allograft inflammatory factor‐1 (AIF‐1) is involved in immune dysfunction and macrophage activation.

Clear cell carcinoma, not otherwise specified, of salivary glands: a clinicopathologic study of 4 cases and review of the literature

Clear cell carcinoma, not otherwise specified (CCC-NOS), is a recently described rare malignant salivary neoplasm. We report the clinicopathologic and immunohistochemical features of 4 cases. The results were then analyzed collectively with the approximate 60 cases of CCC-NOS reported in the English-language literature to define the characteristics of this unusual neoplasm. Combining our cases with those in the literature, a total of 66 cases, confirms that CCC-NOS is a low-grade malignant neoplasm with distinctive clinical and pathologic features. It arises primarily in the minor salivary glands (91% of cases), particularly in the palate or base of tongue, and usually occurs in patients >30 years of age (mean 54.2 years) with a female-to-male ratio of 1.4:1; 12.3% of patients experience local recurrences, 19.3% develop positive regional lymph nodes, 8.8% have distant metastases, and 3.5% die of the disease. Immunohistochemical study focusing on tumor differentiation was performed for our cases, and the findings support the concept that CCC-NOS is of ductal epithelial origin without myoepithelial cell participation.

Epithelial-myoepithelial carcinoma with high grade transformation

Epithelial-myoepithelial carcinoma (EMC) is a rare low-grade salivary gland malignancy of presumed intercalated duct origin comprising 1% of all salivary gland tumours. High grade transformation (HGT) in EMC is a recently recognised entity with only a few cases reported in the literature. The authors report an additional case of EMC with HGT involving the submandibular gland. The patient was a 60-year-old woman who requested examination of the rapid growth of a mass in the left submandibular area, which she had first noticed 20 years previously. Histologically, the tumour had two distinct carcinomatous components. One component had features of a low grade EMC. The second component consisted of polygonal cells, arranged in a solid and nested pattern, with marked nuclear pleomorphism, brisk mitotic activity, and frequent necrosis. The Ki-67 labelling index of the EMC component was 9%, and that of the high grade component was 40%. The patient developed multiple pulmonary metastases 15 months after surgery. The aggressive behaviour of EMC with HGT suggests that it is important to recognise this variant of EMC to avoid misdiagnosis and inappropriate treatment.