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Mitochondrial Mutations in Adenoid Cystic Carcinoma of the Salivary Glands  [PDF]
Suhail K. Mithani,Chunbo Shao,Marietta Tan,Ian M. Smith,Joseph A. Califano,Adel K. El-Naggar,Patrick K. Ha
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0008493
Abstract: The MitoChip v2.0 resequencing array is an array-based technique allowing for accurate and complete sequencing of the mitochondrial genome. No studies have investigated mitochondrial mutation in salivary gland adenoid cystic carcinomas.
Adenoid Cystic Carcinoma of Parotid Salivary Gland—A Case Study  [PDF]
Shuaib Kayode Aremu
Case Reports in Clinical Medicine (CRCM) , 2018, DOI: 10.4236/crcm.2018.711052
Abstract: Adenoid Cystic Carcinoma (ACC) is an infrequent slow growing epithelial tumour constituting for around less than 1% of all the oral and maxillo-facial malignancies and almost 10% of all the salivary gland tumors. Parotid gland is the second most common site to be involved in the head and neck region along with submandibular gland, Palate being the most common site involved in the oral cavity. Key feature of these tumors include its asymptomatic presentation, indolent nature, typically showing infiltrative growth and peri-neural invasion. Herein, we report a case of adenoid cystic carcinoma of right parotid gland of a 33-year-old male who presented with complaint of painless slow enlargement of left parotid gland and facial muscle weakness. On Examination firm mass in the region of the left parotid gland as well as left facial paralysis was seen. Biopsy results and further management is discussed here within.
Immunohistochemical expression of progesterone receptors in adenoid cystic carcinoma and pleomorphic adenoma of salivary glands
Eslami M,Eshghyar N,Ensani F,Seifi S
Journal of Dental Medicine , 2006,
Abstract: Background and Aim: The hormone receptor status in breast cancer has been pivotal in determining the likelihood of response to hormonal manipulation. Tumors which are both estrogen and progesterone receptor positive are much more likely to respond to anti-hormone therapy than negative tumors. There is well-established similarity between breast tissue and salivary glands. The aim of this study was to evaluate the progesterone receptor expression in pleomorphic adenoma and adenoid cystic carcinoma of salivary glands. Materials and Methods: In this descriptive study, immunohistochemical staining with progesterone antibody was performed on 14 pleomorphic adenoma (PA) and 15 adenoid cystic carcinoma (ACC) paraffin blocks. The percentage of positive cells was determined using an eye piece graticule. Immunoreactivity was categorized as either positive (reactivity more than 5%) or negative (reactivity less than 5%). In addition the existence of progesterone receptor in tumor cells, stromal cells (fibroblasts), inflammatory cells and salivary glands around tumors was evaluated. Data were analyzed with T and Mann Whitney U tests with p<0.05 as the limit of significance. Results: Immunohistochemical staining for progesterone receptor was negative in 15 ACC and 13 PA. Only one case of PA showed immunoreactivity for progesterone receptor. Also, 12 normal salivary glands around tumor were positive. Inflammatory cells, endothelial cells and fibroblasts did not show immunoreactivity in most cases. Conclusion: The results indicate the lack of progesterone receptor expression in ACC and PA of salivary glands.
Management of salivary gland adenoid cystic carcinoma: institutional experience of a case series
Tincani, Alfio José;Del Negro, André;Araújo, Priscila Pereira Costa;Akashi, Hugo Kenzo;Martins, Antonio Santos;Altemani, Albina Milani;Barreto, Gilson;
Sao Paulo Medical Journal , 2006, DOI: 10.1590/S1516-31802006000100006
Abstract: context and objective: salivary gland tumor management requires long-term follow-up because of tumor indolence and possible late recurrence and distant metastasis. adenoid cystic carcinoma (acc) accounts for 10-15% of such tumors. the aim here was to evaluate surgical and clinical management, staging and follow-up of acc patients in one academic institution. design and setting: retrospective study at head and neck service, universidade estadual de campinas. methods: data on 21 patients treated between 1993 and 2003 were reviewed. management utilized clinical staging, histology and imaging. major salivary gland tumor extent was routinely assessed by preoperative ultrasonography. diagnosis, surgery type, margin type (negative/positive), postoperative radiotherapy and recurrence (presence/absence) were evaluated. results: there were eleven major salivary gland tumors (52.3%), seven submandibular and four parotid. ten patients (47.7%) had minor salivary gland acc (all in palate), while the submandibular was the most frequently affected major one. diagnoses were mostly via fine-needle aspiration (fna) and incision biopsy. frozen sections were used for six patients. there was good ultrasound/fna correlation. sixteen (76%) had postoperative radiotherapy. one (4.7%) died from acc and five now have recurrent disease: three (14.2%) locoregional and two (9.5%) distant metastases. conclusion: adenoid cystic carcinoma has locally aggressive behavior. in 21 cases, of acc, the facial nerve was preserved in all except in the few with gross tumor involvement. treatment was defined from physical examination, imaging, staging and histology.
MicroRNA Profiling of Salivary Adenoid Cystic Carcinoma: Association of miR-17-92 Upregulation with Poor Outcome  [PDF]
Yoshitsugu Mitani, Dianna B. Roberts, Hanadi Fatani, Randal S. Weber, Merrill S. Kies, Scott M. Lippman, Adel K. El-Naggar
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0066778
Abstract: Background Salivary adenoid cystic carcinoma (ACC) is a rare relentlessly progressive malignant tumor. The molecular events associated with ACC tumorigenesis are poorly understood. Variable microRNAs (miRNA) have been correlated with tumorigenesis of several solid tumors but not in ACC. To investigate the association of miRNAs with the development and/or progression of ACC, we performed a comparative analysis of primary ACC specimens and matched normal samples and a pooled salivary gland standard and correlated the results with clinicopathologic factors and validated selected miRNAs in a separate set of 30 tumors. Methods MiRNA array platform was used for the identification of target miRNAs and the data was subjected to informatics and statistical interrelations. The results were also collected with the MYB-NFIB fusion status and the clinicopathologic features. Results Differentially dysregulated miRNAs in ACC were characterized in comparison to normal expression. No significant differences in miRNA expression were found between the MYB-NFIB fusion positive and -negative ACCs. Of the highly dysregulated miRNA in ACC, overexpression of the miR-17 and miR-20a were significantly associated with poor outcome in the screening and validation sets. Conclusion Our study indicates that the upregulation of miR-17-92 may play a role in the biology of ACC and could be potentially targeted in future therapeutic studies.
Prognostic value of expression of molecular markers in adenoid cystic cancer of the salivary glands compared with lymph node metastasis: a retrospective study  [cached]
Lee Seok Ki,Kwon Min Su,Lee Yoon Se,Choi Seung-Ho
World Journal of Surgical Oncology , 2012, DOI: 10.1186/1477-7819-10-266
Abstract: Background Adenoid cystic cancer arising in the salivary glands has distinctive features such as perineural invasion, distant metastasis, and a variable prognosis. In salivary gland cancer, c-kit, EGFR, and VEGF are representative molecular markers that may predict remnant and recurrent tumors. In this study, the expression of c-kit, EGFR, and VEGF in adenoid cystic cancer was evaluated, and the relationships between the expression of these markers and the clinical findings were investigated. Methods The medical records of 48 patients who were treated for parotid adenoid cystic cancer from January 1990 to January 2006 were reviewed. The tumor location, size, histological subtypes, perineural invasion, the resected margin status, and lymph node metastasis were assessed. Immunohistochemical staining and semiquantitative analysis of c-kit, EGFR and VEGF were performed. The relationship between the expression of each marker and the clinicopathological factors were analyzed. Results Positive c-kit immunostaining was present in 45 patients (94%), with weak positivity (+1) in 23, moderate positivity (+2) in 19 and strong positivity (+3) in three. Positive EGFR immunostaining was observed in 27 (56%), with weak positivity (+1) in 19 and moderate positivity (+2) in eight with no strong positive staining. Positive VEGF immunostaining was present in 42 patients (88%) with weak positivity (+1) in 12, moderate positivity (+2) in 17, and strong positivity (+3) in 13. Only the expression of VEGF was significantly higher in parotid gland tumors than in any other gland (P = 0.032). Marginal involvement was associated with strong VEGF expression (P = 0.02). No marker was significantly correlated with recurrence or the survival rate. Lymph node status was related to the survival rate. Conclusions The expression of c-kit, EGRF, and VEGF had no predictive value for recurrence or the prognosis of adenoid cystic cancer. Only the lymph node status was related to the prognosis.
A 20-Year Retrospective Study of Salivary Gland Adenoid Cystic Carcinoma in a Sample of Iranian Patients  [PDF]
M. Khalili,F. Salamat
Journal of Dentistry of Tehran University of Medical Sciences , 2009,
Abstract: Objective: The aim of the present study was to investigate the demographic and pathological aspects of adenoid cystic carcinomas (ACC) in an Iranian sample based on a 20-year archive review.Materials and Methods: In this descriptive study, tumors of the head and neck registered between 1980 and 2000 were evaluated and cases of ACC were selected. Patients’ medical records and pathology reports were reviewed. Variables such as age, sex, duration of disease,symptoms, site of tumor involvement and tumor diameter as well as pathologic features were recorded. Analysis was performed using chi-square and t-tests; P<0.05 was considered as the level of significance.Results: ACC was the most common malignant tumor followed by mucoepidermoid carcinoma and adenocarcinoma NOS. A total of 120 ACCs were found, of which 50.8% occurred in females and 49.2% in males. Patients’ ages ranged from 5 to 90 with a mean of 49.2 (SD=15.9) years. In 60.9% of cases, minor salivary glands were involved and the palate was the most common site. The greatest tumor diameter was between 2-15cm with a mean of 4.6 cm (SD=2.9). The most prevalent histologic appearance was cribriform, followed by tubular pattern. No significant relation was observed between lymph node metastasisand patients’ age, sex, disease duration, greatest tumor diameter and site of involvement.Conclusion: Our findings were relatively similar to other reports from different parts of the world. Further analytic and case-control studies are recommended to gain a better understanding of different aspects of ACC.
An unusual presentation of adenoid cystic carcinoma of the minor salivary glands with cranial nerve palsy: a case study
Amal Abdul-Hussein, Pierre A Morris, Tsveti Markova
BMC Cancer , 2007, DOI: 10.1186/1471-2407-7-157
Abstract: A 49-year-old African American female presented to the emergency room complaining of severe right-sided headache, photophobia, dizziness and nausea, with diplopia. The patient had a 14 year history migraine headaches, hypertension, and mild intermittent asthma. Physical examination revealed right lateral rectus muscle palsy with esotropia. There was numbness in all three divisions of the right trigeminal nerve. Motor and sensory examination of extremities was normal. An MRI of the brain/brain stem was obtained which showed a large mass in the clivus extending to involve the nasopharynx, pterygoid plate, sphenoid and right cavernous sinuses.Biopsy showed an ACC tumor with a cribriform pattern of the minor salivary glands. The patient underwent total gross surgical resection and radiation therapy.This is a case of ACC of the minor salivary glands with intracranial invasion. The patient had long history of headaches which changed in character during the past year, and symptoms of acute 5th and 6th cranial nerve involvement. Our unique case demonstrates direct invasion of cavernous sinus and could explain the 5th and 6th cranial nerve involvement as histopathology revealed no perineural invasion.Adenoid Cystic Carcinoma (ACC) is a rare tumor entity and comprises about 1% of all malignant tumor of the oral and maxillofacial region [1]. It is a slowly growing but highly invasive cancer with high recurrence rate. Lymphatic spread to local lymph nodes is rare. Hematogenous spread, however, occurs often in the course of the disease [2]. Intracranial ACC even is more rare and has been reported as 4 – 22% of ACC [3]. It could be primary or secondary which could occur either by direct invasion like in our case, hematogenous spread, or perineural spread [4,5]. Perineural spread of ACC has long been recognized. The literature revealed that the region of Gasserian ganglion to be the most common site of involvement (35.8%) [2,3,6,7], while cavernous sinus was involved in 15.1% [3-5
Expression of ERBB3 binding protein 1 (EBP1) in salivary adenoid cystic carcinoma and its clinicopathological relevance
Sun Jian,Luo Yixi,Tian Zhen,Gu Liang
BMC Cancer , 2012, DOI: 10.1186/1471-2407-12-499
Abstract: Background ERBB3 binding protein 1 (EBP1) gene transfer into human salivary adenoid cystic carcinoma cells has been shown to significantly inhibit cell proliferation and reduce tumor metastasis in mouse models. In the current study, to evaluate if EBP1 is a novel biomarker capable of identifying patients at higher risk of disease progression and recurrence, we examined the EBP1 expression profile in adenoid cystic carcinoma (ACC) patients and analyzed its clinicopathological relevance. To understand the underlying anti-metastatic mechanism, we investigated if EBP1 regulates invasion-related molecules. Methods We performed immunohistochemical analysis on 132 primary adenoid cystic carcinoma and adjacent non-cancerous tissues using commercial EBP1, MMP9, E-cadherin and ICAM-1 antibodies. Results were correlated to clinicopathological parameters, long-term survival and invasion-related molecules by statistical analysis. Cell motility and invasiveness of vector or wild-type EBP1-transfected ACC-M cell lines were evaluated using wound healing and Boyden chamber assays. MMP9, E-cadherin and ICAM-1 proteins in these cell lines were detected using western blot assay. Results The expression of EBP1 was significantly higher in non-cancerous adjacent tissues compared with corresponding cancer tissues. The intensity and percentage of cells that reacted with EBP1 antibodies were significantly higher in cases with tubular pattern than those with solid pattern (P<0.0001). We also found adenoid cystic carcinoma with local lymphatic metastasis had significantly lower EBP1 expression than ACC with no local lymphatic node metastasis (P<0.0001). Similar findings were observed in ACC with lung metastasis compared with cases with no lung metastasis (P<0.0001), in particular, in cases with perineural invasion compared with cases with no perineural invasion (P<0.0001). Furthermore, a decrease in EBP1 expression was positively associated with a reduction in overall survival of ACC patients. Of note, EBP1 inhibits migration and invasiveness of ACC cells by upregulating E-cadherin but downregulating MMP9. In clinical adenoid cystic carcinoma patients, higher EBP1 expression was positively correlated with E-cadherin levels (P<0.001) but negatively correlated with MMP9 expression (P=0.0002). Conclusions EBP1 expression is reduced in adenoid cystic carcinoma, indicating unfavorable prognosis of ACC patients. Its regulation of MMP9 and E-cadherin protein levels suggests a critical therapeutic potential.
Reactive Oxygen Species and Autophagy Associated Apoptosis and Limitation of Clonogenic Survival Induced by Zoledronic Acid in Salivary Adenoid Cystic Carcinoma Cell Line SACC-83  [PDF]
Xi-Yuan Ge, Lin-Qian Yang, Yang Jiang, Wen-Wen Yang, Jia Fu, Sheng-Lin Li
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0101207
Abstract: Salivary adenoid cystic carcinoma is an epithelial tumor in the head and neck region. Despite its slow growth, patients with salivary adenoid cystic carcinoma exhibit poor long term survival because of a high rate of distant metastasis. Lung and bone are common distant metastasis sites. Zoledronic acid, a third generation bisphosphonate, has been used for tumor-induced osteolysis due to bone metastasis and has direct antitumor activity in several human neoplasms. Here, we observed that zoledronic acid inhibited salivary adenoid cystic carcinoma cell line SACC-83 xenograft tumor growth in nude mice. In vitro, zoledronic acid induced apoptosis and reduced clonogenic survival in SACC-83. Flow cytometry and western blotting indicated that the cell cycle was arrested at G0/G1. Zoledronic acid treatment upregulated reactive oxygen species as well as the autophagy marker protein LC-3B. Reactive oxygen species scavenger N-acetylcysteine and autophagy antagonist 3-methyladenine decreased zoledronic acid-induced apoptosis and increased clonogenic survival. Silencing of the autophagy related gene Beclin-1 also decreased zoledronic acid-induced apoptosis and inhibition of clonogenic formation. In addition, isobolographic analysis revealed synergistic effects on apoptosis when zoledronic acid and paclitaxel/cisplatin were combined. Taken together, our results suggest that zoledronic acid induced apoptosis and reduced clonogenic survival via upregulation of reactive oxygen species and autophagy in the SACC-83 cell line. Thus, zoledronic acid should be considered a promising drug for the treatment of salivary adenoid cystic carcinoma.
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