|Year : 2009 | Volume
| Issue : 1 | Page : 51-53
Fathima S Shabana, K Manjunath
Department of Oral and Maxillofacial Pathology, Meenakshi Ammal Dental College, Chennai, India
Fathima S Shabana
Department of Oral and Maxillofacial Pathology, Meenakshi Ammal Dental College, Chennai
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Shabana FS, Manjunath K. Journal Reviews. J Oral Maxillofac Pathol 2009;13:51-3
Dysregulation of Wnt0 pathway components in human salivary gland tumors
Queimado L, Obeso D, Hatfield MD, Yang Y, Thompson DM, Reis AMC
Arch Otolaryngol Head Neck Surg 2008;134(1):94-101.
A complex of intracellular and extracellular components regulate the activity of Wnt pathway. β-Catenin is a key mediator of Wnt0 activity. Expression of β-catenin isincreased by mutations in the Wnt intracellular signaling pathway and may contribute to the development and progression of various tumours. Similary a down-regulation of Wnt0 antagonists like Wnt0 inhibitory factor ( WIF1 ) and/or overexpression of secreted Wnt agonists (WNT proteins) may also play a role in pathogenesis of various tumours.
In this study, the investigators have analyzed the expression of WIF1, WNT1, and β-catenin in tumour cell lines established from pleomorphic adenomas (PA30,PA37, PA54, PA116 and PA125), carcinoma ex pleomorphic adenoma (CaPA79), epithelial-myoepithelial carcinoma (EMC23), mucoepidermoid carcinoma (MEC49), and adeniod cystic carcinomas (ACC52 and ACC112) by reverse transcription-polymerase chain reaction and Western blot analysis.
They found a higher level of expression of WIF1 in normal salivary gland and significant down-regulation of WIF1 in all salivary gland tumor cell lines. This finding was supported by an upregulation of WNT1 protein and β-catenin messenger RNA expression in all salivary gland tumour cell lines. They hypothesized that loss of negative and gain of positive WNT signals in the human benign salivary gland tumors might have an additive effect in salivary gland oncogenesis and perhaps be a hallmark of progression to malignancy. The data of this study indicate that the WNT pathway may be a potential therapeutic target in human salivary gland cancer.
Clinical utility of 18 F-FDG PET for patients with salivary gland malignancies
Roh JL, Ryu CH, Choi SH, Kim JS, Lee JH, Cho KJ, et al.
The Journal of Nuclear Medicine 2007;28(2):240-246.
Pre-surgical assessment of salivary gland tumours may be performed by clinical evaluation, computerized tomography, magnetic resonance imaging or fine needle aspiration biopsy. Recently, 18 F-FDG PET (Fluorodeoxyglucose Positron Emission Tomography) has been reported to be superior to conventional imaging in evaluation of head and neck malignancies. But the utility of 18 F-FDG PET in evaluation of salivary gland tumours needs to be investigated.
In this study the role of 18 F-FDG PET in preoperative staging, histological grading, and prediction of therapeutic outcome in patients with salivary gland malignancies was carried out in patients with newly diagnosed salivary gland cancers. The diagnostic accuracies of CT and 18 F -FDG PET for detecting primary tumors and neck metastases were compared with a histopathologic reference. The relationship between the maximum standardized uptake value (SUV) of the tumor and clinicopathologic parameters such as sex, age, local tumor invasion, T and N categories, TNM stage, and histologic grade, as well as their association with disease-free survival (DFS) were also analysed. Their results showed 18 F -FDS PET was more sensitive than CT for the detection of primary tumors (91.2% vs. 79.4%; P < 0.05), cervical metastases (80.5% vs. 56.1%; P <0.05), and distant metastases at initial staging. High- grade malignancies had higher mean maximum SUVs than did low- and intermediate- grade malignancies (4.6 vs. 2.8; P =0.011). T and N categories were independent determinants of DFS. During a mean follow-up of 25.1 months, 18 F -FDS PET was found to correctly diagnose local-regional recurrences and new distant metastases. It can inferred from this study that in patients with salivary gland malignancies, 18 F -FDS PET is clinically useful in initial staging, histological grading, and monitoring after treatment but not in predicting patient survival.
Apparent diffusion coefficient mapping of salivary gland tumors: Prediction of the benignancy and malignancy
Eida S, Sumi M, Sakihama N, Takahashi H, Nakamura T
AJNR Am J Neuroradiol 2007;28:116-121.
Preoperative prediction of the malignancy or benignancy of salivary gland tumor is clinically very important and strongly influences the surgical plan. Although conventional T1-and T2- weighted MR imaging techniques with or without gadolinium enhancement have been used for the diagnosis of salivary gland tumors, many investigators have reported that differentiation of salivary gland tumors, especially between benign and low-grade malignant tumors, is often difficult. Analyzing a large region of interest in a histologically heterogeneous tumor may therefore result in spurious results with regard to the tumor histology. To avoid this potential error, tissue characterization using high-resolution magnetic resonance imaging (HR-MRI) techniques seems mandatory.
In this study the preoperative apparent diffusion coefficient (ADC) maps of benign and malignant salivary gland tumors were analysed using HR-MRI. The ADCs were compared with histologic features of the excised tumors. The ADC maps effectively depicted the histological features in pleomorphic adenomas with ADC level being intermediate and large areas with high ADC that correspond to cystic or myxomatous lesions. Warthin's tumour showed heterogeneous ADC levels and areas with intermediate ADC corresponding to necrosis, and areas with low ADC indicating cyst formation among the lymphoid tissues. Similarly in mucoepidermoid carcinoma, the ADC map demonstrated relatively homogenous areas of low ADCs, corresponding to tumor areas with polygonal or round-cell proliferation. Adenocarcinoma and adenoid cystic carcinoma exhibited speckled patterns on ADC maps for indicating low to high ADCs. The heterogeneity on ADC maps indicated small necrotic or cystic areas distributed in the tumors. Malignant lymphomas arising in the salivary glands were associated with extremely low ADCs throughout the lesions; this was consistent with the homogenous growth patterns of lymphoma cells. The sensitivity and specificity for high ADC occupying fewer than 5% of the area of a tumor was 89% and 100%, respectively, resulting in 97% accuracy, 100% positive predictive value, and 96% negative predictive value. So, ADC may provide preoperative tissue characterization of the salivary gland tumors.
Nuclear hBD-1 accumulation in malignant salivary gland tumours
Wenghoefer M, Pantelis A, Dommisch H, Gφtz W, Reich R, Bergι S, et al.
BMC Cancer 2008; 8:290.
Human beta defensins (hBD) such as hBD-1, -2, -3 are positively charged peptides with molecular weights ranging from 3.5 to 6.5 kDa. The ability of hBD to disintegrate membranes is responsible for their antimicrobial potency against a number of gram-positive and gram-negative bacteria as well as yeasts and certain viruses. Defensins have been detected in the epithelia of the oral cavity, vagina, gastrointestinal, respiratory and urinary tract as well as in salivary glands. Presence of defensins in the submandibular glands of patients with oral carcinomas indicate their role in tumour immunity and disintegration of tumour cells. hBD-2 and -3 seem to be related to inflammation. hBD-1 might function as 8p tumour suppressor gene and thus play a key role in control of transcription and induction of apoptosis in malignant epithelial tumors.
In this study, the investigators examined immunohistochemical expression of p53, bcl-2, and hBD-1, -2, -3 in benign and malignant salivary gland tumours. hBD-1 was distributed in the cytoplasm of healthy salivary glands and benign salivary gland tumours but seems to migrate into the nucleus of malignant salivary gland tumours. Pleomorphic adenomas showed cytoplasmic as well as weak nuclear hBD-1 staining. This study concluded that, hBD-1, 2 and 3 are traceable in healthy salivary gland tissue as well as in benign and malignant salivary gland tumours. As hBD-1 is shifted from the cytoplasm to the nucleus in malignant salivary gland tumours, they hypothesized that it might play a role in the oncogenesis of these tumours. In pleomorphic adenomas hBD-1 might be connected to their biologic behavior of recurrence and malignant transformation.
X-ray repair cross-complementing Group 1 (XRCC1) single-nucleotide polymorphisms and the risk of salivary gland carcinomas.
Ho T, Li G, Lu J, Zhao C, Wei Q, Sturgis EM
Single-strand DNA breaks could occur due to exposure to endogenously produced reactive oxygen species or exogenous carcinogens. These breaks are repaired by a DNA base excision repair process by various proteins which include x-ray repair cross-complementing group 1 (XRCC1), DNA ligase III, and DNA polymerase β.
In this study six XRCCI single-nucleotide polymorphisms (SNPs) were analysed in benign and malignant salivary gland tumours using polymerase chain reaction restriction fragment lenghth polymorphism. They found the XRCC1 genotype distributions to differ significantly among patients with malignant salivary gland tumours and controls for both the T1915C promoter SNP and Arg194Trp coding region SNP. The polymorphic 1915C allele was significantly less frequent in patients with malignant salivary gland tumours than in the controls. Using multivariate analysis they found that individuals who had the 1915 polymorphic homozygous CC genotype had a significantly lower risk for malignant salivary gland tumours, and individuals who had the Arg194Trp heterozygous CT genotype had a higher, borderline significant risk. The CGTTGG haplotype was associated with a higher risk for malignant salivary gland tumours. On the other hand they found that none of the SNPs were significant for the patients who had benign salivary gland tumors.
Cimetidine inhibits salivary gland tumor cell adhesion to neural cells and induces apoptosis by blocking NCAM expression
Fukuda M, Kusama K, Sakashita H
BMC Cancer 2008, 8:376.
The growth of glandular tumors such as colorectal cancer has been reported to be inhibited by cimetidine, a histamine type-2 receptor antagonist. Adenoid cystic carcinoma is known preferentially invade neural tissues and is frequently associated with facial paralysis. Inhibition of perineural/neural invasion could be used as a strategy for arresting the development of adenoid cystic carcinoma. Human salivary gland tumor (HSG) cells spontaneously express neural cell adhesion molecule (NCAM). Proliferation of HSG cell may be controlled via a homophilic (NCAM-NCAM) binding mechanism and that NCAM may be associated with perineural invasion by malignant salivary gland tumors.
In this study, the effect of cimetidine on cancer cell adhesion to neural cells was examined in vitro and had also used an in vivo carcinogenesis model to confirm the effect of cimetidine. This study demonstrated that cimetidine can block the adhesion of HSG cells to neural cell monolayers and that it can also induce significant apoptosis in the tumor mass in a nude mouse model. They also demonstrated that these apoptotic effects of cimetidine might occur through down-regulation of the cell surface expression of NCAM on HSG cells. Cimetidine-mediated down-regulation of NCAM involved suppression of the nuclear translocation of NF-κB (Nuclear factor Kappa B), a transcriptional activator of NCAM gene expression. This suggests that growth and perineural/neural invasion of salivary gland tumors can be blocked by administration of cimetidine.