Chun-Ye Zhang

Promoter Methylation as a Common Mechanism for Inactivating E-cadherin in Human Salivary Gland Adenoid Cystic Carcinoma

The role of promoter methylation in the inactivation of E‐cadherin (E‐cad) in salivary gland adenoid cystic carcinoma (ACC) is unknown. The objective of this study was to determine the role and potential clinical implications of promoter methylation of E‐cad in salivary gland ACC.

Adenoid cystic carcinoma of the head and neck: clinicopathologic analysis of 218 cases in a Chinese population.

OBJECTIVE The aim of this study was to analyze the clinicopathologic characteristics and prognostic factors of adenoid cystic carcinoma of the head and neck (ACCHN). STUDY DESIGN This was a retrospective study of 218 patients with ACCHN. RESULTS The cohort included 110 men and 108 women; the parotid and the palate were the most common site of involvement. Of 203 patients with follow-up information (range 2-132 months), 57 had died of the tumor. Distant metastasis (DM) and local recurrence (LR) were documented in 83 (40.9%) and 34 (16.7%) patients, respectively. Cox regression analysis indicated that a solid pattern was a marker for LR and that positive margins and older age were risk factors for DM. Histologic pattern, T stage, N stage, LR, DM, and patient age contributed to the prediction of disease-specific survival. CONCLUSIONS A solid pattern, metastasis, LR, and older age are the most important factors for predicting poor prognosis in Chinese patients with ACCHN.

High Expression of H3K9me3 Is a Strong Predictor of Poor Survival in Patients With Salivary Adenoid Cystic Carcinoma

CONTEXT Histone methylation and acetylation play important roles in the carcinogenesis and progression of cancer. OBJECTIVE To investigate whether histone modifications influence the prognosis of patients with salivary adenoid cystic carcinoma (ACC). DESIGN The expression of histone H3 lysine 9 trimethylation (H3K9me3) and histone H3 lysine 9 acetylation (H3K9Ac) was assessed by immunohistochemistry in 66 specimens of primary ACC. Tests were used to determine the presence of any correlation between H3K9me3 and H3K9Ac levels and clinicopathologic parameters. Log-rank test and Cox proportional hazards regression models were used to analyze the survival data. RESULTS H3K9me3 expression was positively correlated with solid pattern tumors (P = .002) and distant metastasis (P = .001). Solid pattern tumors had lower H3K9Ac expression levels than cribriform-tubular pattern tumors (P = .03). Patients whose tumors showed high H3K9me3 expression and a solid pattern had a significantly poorer overall survival (OS) (P < .001 and P < .001, respectively) and disease-free survival (P < .001 and P = .01, respectively). Low H3K9Ac expression was correlated with poor OS (P = .05). The multivariate analysis indicated that high levels of H3K9me3 expression and solid pattern tumors were independent prognostic factors that significantly influenced OS (P = .004 and P = .04, respectively). H3K9me3 expression was identified as the only independent predictor of disease-free survival (P = .006). CONCLUSIONS Our results suggest that high levels of H3K9me3 expression are predictive of rapid cell proliferation and distant metastasis in ACC. Compared with histologic patterns, H3K9me3 might be a better predictive biomarker for the prognosis of patients with salivary ACC.

Aberrant protein expression and promoter methylation of p16 gene are correlated with malignant transformation of salivary pleomorphic adenoma.

CONTEXT The significance of promoter methylation of the p16 gene and intracellular localization of p16 protein in the carcinogenesis of salivary carcinoma ex pleomorphic adenoma (Ca-ex-PA) is not clear. The correlation of the promoter methylation of the p16 gene and the expression and localization of p16 protein in Ca-ex-PA need to be further clarified. OBJECTIVE To investigate the p16 protein expression and promoter methylation of p16 gene in Ca-ex-PA and their roles in the malignant transformation of pleomorphic adenoma to Ca-ex-PA. DESIGN The p16 protein expression and promoter methylation of the p16 gene were determined in both benign and malignant components of 50 primary salivary Ca-ex-PA tissues by immunohistochemistry and methylation-specific polymerase chain reaction. Expression of p16 protein and promoter methylation of the p16 gene between the benign and the malignant components was compared statistically. RESULTS The tumor cells in the malignant components showed significantly higher p16 protein expression in the cytoplasm and lower expression in the nuclei than those in the benign components. Promoter methylation frequency of the p16 gene in the malignant components (36%) was significantly higher than that in the benign components (16%). There were no correlations between p16 protein expression and promoter methylation of the p16 gene in either benign or malignant components. CONCLUSIONS Overexpression of p16 protein in the cytoplasm and decreased expression of p16 protein in the nucleus may play important roles in the evolution of pleomorphic adenoma to Ca-ex-PA. Promoter methylation of the p16 gene may be correlated with the malignant transformation of pleomorphic adenoma.

RASSF1A Promoter Hypermethylation Is a Strong Biomarker of Poor Survival in Patients with Salivary Adenoid Cystic Carcinoma in a Chinese Population

In addition to the clinicopathological parameters, molecular biomarkers are becoming increasingly important in the prognostic evaluation of cancer patients. This study aimed to determine the molecular alterations in the RAS association domain family protein1A gene (RASSF1A) in salivary adenoid cystic carcinoma (ACC) and to evaluate the potential of such alterations as prognostic markers. One hundred and sixty-seven ACC tumor tissues and 50 samples of matched normal salivary gland tissues from the same patients were analyzed for RASSF1A promoter methylation status by bisulfite sequencing PCR (BSP) and/or methylation-specific PCR (MSP). Fifty ACC tumor tissues and matched normal salivary gland tissues were analyzed for loss of heterozygosity (LOH) by examining two microsatellite markers (D3S1478, D3S1621) at 3p21. RASSF1A gene mutations were detected by direct sequencing of all six exons in 50 tumor and normal tissue specimens. Over-all, RASSF1A promoter hypermethylation was detected in 35.3% (59/167) of ACC tissues and was associated with histologically solid tumor pattern (P = 0.002) and advanced TNM stage (P = 0.014). RASSF1A LOH was observed in 18.0% (9/50) of cases, and no somatic mutation of RASSF1A was detected in any cases. RASSF1A promoter methylation was associated with the poor over-all survival (Log-rank test, P <0.001) and disease-free survival (Log-rank test, P <0.001) and identified as an independent predicator of over-all patient survival (P = 0.009) and disease-free survival (P <0.001). It was concluded that RASSF1A methylation is involved in the development, differentiation and progression of ACC and is a strong independent biomarker of poor survival in ACC patients in a Chinese population.

An unusual cribriform variant of salivary basal cell tumours: a clinicopathological study of 22 cases

Tian Z, Hu Y, Wang L, Li L, Zhang C & Li J 
(2012) Histopathology 61, 921–929

Prognostic factors of carcinoma ex pleomorphic adenoma of the salivary glands, with emphasis on the widely invasive carcinoma: a clinicopathologic analysis of 361 cases in a Chinese population

OBJECTIVES To analyze the clinicopathologic characteristics and prognostic factors of salivary carcinoma ex pleomorphic adenoma (Ca-ex-PA) and widely invasive Ca-ex-PA in a Chinese population. STUDY DESIGN The clinicopathologic parameters of 361 patients with primary Ca-ex-PA from our 2001-2012 cohort were retrospectively reviewed, and the correlation between the parameters and disease-specific survival was statistically analyzed. RESULTS Of 361 patients with Ca-ex-PA, 229 were male, 132 were female. 191 tumors were invasive carcinoma, 77 minimally invasive, and 93 noninvasive. For 334 (93%) patients, follow-up information was available, and only one of 160 patients with noninvasive or minimally invasive Ca-ex-PA died as a result of the tumor. Of 174 patients with widely invasive Ca-ex-PA, 54 (31%) died as a result of the tumor. Using the Kaplan-Meier method, age, T stage, N stage, histologic grade, and proportion of carcinoma were found to be significantly associated with disease-specific survival of widely invasive Ca-ex-PA. Cox regression analysis indicated that T stage and N stage were independent prognostic factors of disease-specific survival of widely invasive Ca-ex-PA. CONCLUSIONS Widely invasive Ca-ex-PA had a much worse clinical outcome compared with noninvasive or minimally invasive Ca-ex-PA. T stage and N stage are the most important independent factors for predicting prognosis in Chinese patients with widely invasive Ca-ex-PA.

Oral carcinoma cuniculatum presenting with moth-eaten destruction of the mandible

OBJECTIVE Carcinoma cuniculatum (CC) is a rare variant of squamous cell carcinoma. We describe the clinicopathologic findings in a new case. STUDY DESIGN This is a literature review and retrospective study of a case with CC. RESULTS The clinical and imaging findings of CC are diverse; some cases might be challenging to diagnose accurately by biopsy. This article reports a case of CC that occurred in the retromolar region with involvement of the mandible. The patient was a 39-year-old man. Clinically, the lesion manifested as an ulcerative mass in the mandibular molar region. Imaging results showed that the lesion in the jaw exhibited moth-eaten destruction without obvious expansion of the jaw bone. The postoperative pathologic examinations were consistent with CC; additionally, metastases were present in 1 level II lymph node and 1 submandibular lymph node. Left soft tissue metastasis and right cervical lymph node metastases were detected 10 and 27 months after surgery, respectively. CONCLUSIONS CC is a rare epithelial malignant tumor and has variable clinical manifestations. The diagnosis of CC mainly depends on pathologic features. Most patients with CC have a good prognosis; only a small percentage of patients might experience lymph node metastasis.

A low percentage of HER-2 amplification whereas indicates poor prognosis in salivary carcinoma ex pleomorphic adenoma: a study of 140 cases

BACKGROUND Human epidermal growth factor receptor 2 (HER-2) has been found in many malignant tumours including salivary malignancy. HER-2-targeted therapy has been applied in the treatment of HER-2-overexpressing carcinoma. The aim of this study was to determine the status of HER-2 in salivary invasive carcinoma ex pleomorphic adenoma (ICXPA) in a relatively large Chinese sample, which may provide HER-2-targeted therapy with profound support in the future. METHODS AND RESULTS We collected 140 ICXPAs and their related clinicopathological and follow-up data. All cases were examined for HER-2 expression by immunohistochemistry and gene amplification by fluorescence in situ hybridization, if necessary. The study showed that the ratio of HER-2 positivity was only 25% (35/140) in all cases, but the positive ratio in ICXPAs with luminal differentiation for malignant component (32/79, 40.5%) was much higher than that in cases with non-luminal differentiation (3/61, 4.9%). The overexpression of HER-2 was closely associated with gender, histological grade and N stage. HER-2-positive tumours conferred short overall survival time (P = 0.036) and short disease-specific survival time (P = 0.042) in patients, but HER-2 status was not an independent predictor of prognosis. CONCLUSIONS Human epidermal growth factor receptor 2 amplification is significantly associated with cell differentiation of the malignant component in ICXPA and it implies an unfavourable prognosis. Although HER-2 positivity is not common in the tumour, HER-2-targeted therapy for those HER-2-positive patients is still worth expecting.

Prognostic nomogram for disease-specific survival of carcinoma ex pleomorphic adenoma of the salivary gland

The purpose of this study was to establish an effective prognostic nomogram for carcinoma ex pleomorphic adenoma (Ca‐ex‐PA) of the salivary gland.