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At least 847 records · Page 47Linked to original sources
PubMed2004

Imatinib mesylate as treatment for adenoid cystic carcinoma of the salivary glands: report of two successfully treated cases.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a malignant neoplasia of the salivary glands that is treated primarily by surgery. Local control and survival are usually compromised despite surgery. Expression of KIT tyrosine kinase is involved in the pathogenesis of ACC. Imatinib mesylate is a potent inhibitor of KIT tyrosine kinase, so we explored the possibility that ACC could be a potential target for this drug. METHODS: We report two cases of unresectable ACC treated with imatinib mesylate in the context of recurrent disease (case 1) and locally advanced tumor at its initial presentation (case 2). RESULTS: Both patients responded well to treatment with imatinib mesylate. Significant regression of recurrent disease (case 1) resulted in a successful salvage surgical resection; the locally advanced tumor (case 2) had an excellent response to treatment, but, unfortunately, the patient refused salvage resection. CONCLUSION: This is the first time ACC is reported to respond to imatinib mesylate. Studies in which more patients are enrolled in controlled clinical trials are needed to confirm this observation.

Antineoplastic Agents↗
PubMed2005

Unexpected rapid progression of metastatic adenoid cystic carcinoma during treatment with imatinib mesylate.

BACKGROUND: There is a lack of effective treatment for metastatic adenoid cystic carcinoma (ACC), a usually indolent tumor. We studied the efficacy of imatinib mesylate, a potent inhibitor of KIT tyrosine kinase, in patients with KIT-positive metastatic ACC. METHOD: Five patients with lung metastasis were treated in a pilot study with imatinib 400 mg by mouth twice a day. Mutations of c-kit and platelet-derived growth factor receptor (PDGFR)-alpha in tumors from these patients were analyzed. RESULTS: Disease progression was noted in three of five patients during the short treatment periods, ranging from 2 to 3 weeks. Three patients died of disease within 6 months. No detectable mutations were found in c-kit and PDGFR-alpha. CONCLUSION: We observed an unexpected high progression rate of metastatic ACC within short periods during imatinib treatment. Use of imatinib to treat cancers without c-kit or PDGFR-alpha mutation should be approached with caution.

Administration, Oral↗
PubMed2005

c-kit expression in adenoid cystic carcinoma does not have an impact on local or distant tumor recurrence.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a neoplasm with unpredictable behavior with frequent late relapses that lacks good prognostic indicators. c-kit tyrosine kinase oncogene has recently been found to be expressed in ACC. The aim of this study is to correlate the expression of c-kit in ACC with clinical follow-up. METHODS: Paraffin sections of 45 cases of ACC diagnosed during a 15-year period were immunostained for c-kit. RESULTS: Seventy-eight percent of tumors stained positive for c-kit. Mean follow-up time was 6 years. No degree/pattern of c-kit expression correlated to local or distant tumor recurrence. However, there was a significant association between surgical margin involvement by tumor and cell membrane expression of c-kit. Staining quality was not affected by storage time. CONCLUSIONS: Our results suggest that expression of c-kit may not serve as a useful marker for predicting outcome in ACC, although they need to be confirmed in a larger patient population with longer clinical follow-up.

Adult↗
PubMed2007

Aberrant cytokine expression in serum of patients with adenoid cystic carcinoma and squamous cell carcinoma of the head and neck.

BACKGROUND: Squamous cell carcinoma (SCC) and adenoid cystic carcinoma (ACC) represent 2 clinically important subtypes of head and neck cancer. Our objective was to characterize and compare cytokine profiles in the systemic circulation of patients with SCC and ACC. METHODS: Multiplex analysis of 10 different cytokines (interleukin [IL]-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor [GM-CSF], interferon [IFN]-gamma, and tumor necrosis factor [TNF]-alpha) in the serum of patients with SCC (n = 20) and ACC (n = 20) and healthy controls (n = 20) was performed using the Luminex fluorescent-bead technology. RESULTS: Patients with SCC as well as patients with ACC showed an altered cytokine profile compared with healthy individuals. In patients with SCC, significantly elevated serum levels of the proinflammatory cytokines, IL-6 and IL-8, were observed. In patients with ACC, IL-8 serum levels were significantly elevated, and IL-6 serum levels were only increased in a subset of patients. CONCLUSIONS: A similar serum cytokine profile, with the predominance of proinflammatory cytokines, was observed in patients with SCC and ACC. The newly defined cytokine profile in ACC patients may form the basis for future investigations to explore the role of cytokines in ACC tumor progression and their potential value as predictive biomarkers.

Adult↗
PubMedDate not supplied

Intraoral adenoid cystic carcinoma: the role of postoperative radiotherapy in local control.

Fourteen cases of adenoid cystic carcinoma (ACC) of the intraoral salivary glands with positive surgical margins have been reviewed in order to determine the role of postoperative radiotherapy in local control. Since local control was obtained in all patients, postoperative radiotherapy seems an adequate treatment to deal with the problem of positive surgical margins at the microscopic level, in cases of intraoral ACC, making additional surgical treatment redundant.

Adult↗
PubMedDate not supplied

Cisplatin-based chemotherapy in advanced adenoid cystic carcinoma of the head and neck.

Nineteen patients, nine men and 10 women, with advanced adenoid cystic carcinoma (ACC), were treated with cisplatin either alone or in combination with doxorubicin and bleomycin. Median age was 51 years (range: 32-73 years). Two groups of patients were distinguished: Group 1 (N = 10) received single-agent cisplatin (50-120 mg/m2 IV every 4 weeks) for locoregional recurrence (N = 4), pulmonary metastases (N = 5), or as neoadjuvant therapy (N = 1). Five patients failed previous chemotherapy. No objective responses were observed, five patients showed stabilization of their disease for a median duration of 20 months (range: 3-50 months). Group 2 (N = 9) received a combination of cisplatin (20 mg/m2 IV on days 1-5), doxorubicin (50 mg/m2 IV on day 1), and bleomycin (30 mg IV on days 1-5), every 3 weeks. A complete remission (CR) was seen in one patient, lasting for 2 years, a partial remission (PR) in two patients (duration: 6 months and 6 years) (33%), and a stable disease (SD) in five patients (median duration: 15 months; range 3-24 months). One patient showed progression from the start. The observed toxicity was acceptable: dose reduction was required in five patients for myelosuppression or impairment of renal function; vomiting grade III (WHO) was seen in 10 patients. The median progression-free survival was 36 months (range: 7-77 months). Median overall survival was 81 months (range: 14-216 months). The role of cisplatin in this disease remains questionable.

Adult↗
PubMedDate not supplied

Elevated carcinoembryonic antigen levels correlating with disease recurrence in a patient with adenoid cystic carcinoma.

BACKGROUND: Carcinoembryonic antigen (CEA) is an oncofetal glycoprotein involved in cell recognition and adhesion. Serum CEA has been extensively studied as a potential chemical marker for malignancy, most notably in patients with colon carcinoma. Serum CEA measurements have not been reported for patients with salivary gland carcinomas. METHODS: Serum CEA was measured in a case study using enzyme immunoassay with monoclonal antibody specific for CEA. Tissue was examined with standard histologic and immunohistologic methods. RESULTS: A patient was initially seen with adenoid cystic carcinoma (ACC) of the trachea and had a markedly elevated serum CEA level which declined after surgical resection. The serum CEA level became elevated again when the patient developed abdominal metastases and then declined after debulking of the tumor. Immunohistochemical study of the tumor was positive for CEA. CONCLUSIONS: The measurement of serum CEA levels may play a role in the management of patients with ACC. Clinical investigation utilizing monoclonal antibodies against CEA, for imaging and for the delivery of chemotherapy and radiotherapy may be worthwhile.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Adenoid cystic salivary gland carcinoma: a clinicopathologic correlation.

Between 1960 and 1980, 71 cases of adenoid cystic carcinoma (ACC) were reviewed according to treatment modality and clinical course. Histologic review of pathologic slides was performed to classify the tumors into their predominant histologic pattern (tubular, cribriform, solid). The predominant histologic patterns of the tumors were equally divided between tubular and cribriform. Very few were classified as a solid pattern. In the patients receiving the same type of therapy (surgery and irradiation), the cribriform and tubular variants of ACC demonstrated no difference in the rate of distant metastases and overall survival. The cribriform variant demonstrated a significantly worse prognosis in terms of local recurrence rate. The patients who had a solid histologic pattern of ACC appeared to have an overall worse prognosis in terms of distant metastases and long-term survival. The long-term survival of patients with ACC may be related to the development of distant metastases despite local control.

Carcinoma, Adenoid Cystic↗
PubMed2001

Adenoid cystic carcinoma: a retrospective clinical review.

Adenoid cystic carcinoma (ACC) are uncommon tumors, representing about 10% to 15% of head and neck tumors. We compare the survival and control rates at our institution with those reported in the literature, and examine putative predictors of outcome. All patients registered with the tumor registry as having had ACC were identified. Demographic and survival variables were retrieved from the database. Additionally, a chart review of all patients was done to obtain specific information. Minor gland tumors were staged using the American Joint Committee on Cancer's criteria for squamous cell carcinomas in identical sites. Histopathologic variables retrieved included grade of the tumor, margins, and perineural invasion. Treatment modalities, field sizes, and radiation doses were recorded in applicable cases. An effort to retrieve archival tumor specimens for immunohistochemical analysis was undertaken. A total of 69 patients were treated for ACC from 1955 to 1999. One patient, who presented with fatal brain metastasis, was excluded from further analysis. Of the remaining 68 patients, 30 were men and 38 were women. The average age at diagnosis was 52 years, and mean follow-up was 13.2 years. Mean survival was 7.7 years. Overall survival (OS) rates at 5, 10, and 15 years were 72%, 44%, and 34%, and cause-specific survival was 83%, 71%, and 55%, respectively. Recurrence-free survival rates were 65%, 52%, and 30% at 5, 10, and 15 years, with a total of 29 of 68 (43%) eventually suffering a recurrence. Overall survival was adversely affected by advancing T and AJCC stage. Higher tumor grades were also associated with decreased OS, although the numbers compared were small. Primaries of the nasosinal region fared poorly when compared with other locations. Total recurrence-free survival, local and distant recurrence rates were distinctly better in primaries of the oral cavity/oropharynx when compared with those in other locations. Reduced distant recurrence-free survival was significantly associated with increasing stage. No other variables were predictive for recurrence. Additionally, we found that nasosinal tumors were more likely to display higher stage at presentation, and were more often associated with perineural invasion. Also of interest was the association of perineural invasion with margin status, with 15 of 20 patients with positive margins displaying perineural invasion, while only 5 of 17 with negative margins showed nerve invasion (P = 0.02). On immunohistochemistry, 2 cases of the 29 (7%) tumor specimens found displayed HER-2/neu positivity. No correlation between clinical behavior and positive staining could be demonstrated. Our data concur with previous reports on ACC in terms of survival and recurrence statistics. Stage and site of primary were important determinants of outcome. Grade may still serve a role in decision making. We could not demonstrate any differences attributable to primary modality of therapy, perhaps due to the nonrandomization of patients into the various treatment tracks and the inclusion of palliative cases. Similarly, perineural invasion, radiation dose and field size, and HER-2/neu positivity did not prove to be important factors in our experience.

Carcinoma, Adenoid Cystic↗
PubMed2006

Protein expression profiling identifies maspin and stathmin as potential biomarkers of adenoid cystic carcinoma of the salivary glands.

Adenoid cystic carcinoma (ACC) is one of the most common malignant tumors of the salivary glands. It tends to grow slowly but is associated with a poor prognosis compared to other malignant salivary gland tumors. To identify specific markers of ACC, we examined protein expression profiling in ACC xenograft and normal salivary glands (NSG) using fluorescent 2-dimensional differential in-gel electrophoresis (2-D-DIGE), an emerging technique for comparative proteomics, that improves the reproducibility and reliability of differential protein expression analysis between the samples. To identify the proteins, matrix-assisted laser desorption/ionization time-of-flight peptide mass fingerprinting was carried out. Using these strategies, we detected 4 upregulated proteins and 5 downregulated proteins in ACC xenograft. Maspin and stathmin were selected for further analyses. Western blotting and immunohistochemical staining showed a higher expression of these proteins in ACC xenograft and clinical ACC tissue compared to NSG. Furthermore, Expression of these proteins was correlated with the histologic grading of ACC (n = 10). Therefore, our data indicate that maspin and stathmin may be not only useful biomarkers of ACC but also markers of biologic behavior in this tumor.

Animals↗
PubMed2005

Expression of the urokinase receptor regulates focal adhesion assembly and cell migration in adenoid cystic carcinoma cells.

Adenoid cystic carcinoma (AdCC) cell lines (ACCS and ACCT) showed higher migration responses and adhesion to the extracellular matrix (ECM), especially types I and IV collagen, than did the oral squamous cell carcinoma (SCC) lines (NA and TF). The response to collagens was largely and exclusively inhibited by anti-alpha(2) integrin antibody. Moreover, AdCC cell lines expressed higher surface levels of urokinase-type plasminogen activator receptor (uPAR) than did SCC cell lines. When AdCC cells were plated on collagen, the surface level of uPAR was increased, and numerous focal adhesions consisting of uPAR, vinculin, and paxillin were assembled; whereas collagen-stimulated SCC cell counterparts or AdCC cells plated on other types of ECM, such as fibronectin, failed to assemble such definite focal adhesions. In order to elucidate the association of uPAR with collagen-induced events, an ACCS-AS cell line transfected with a vector expressing antisense uPAR RNA was established and shown to have reduced uPAR (about 10% that of parental ACCS at both the protein and mRNA levels). ACCS-AS showed a strong reduction of collagen-stimulated migration and focal adhesion assembly of alpha(2) integrin, vinculin, and paxillin. These findings suggest that AdCC has a proclivity for migrating to types I and IV collagens due to the overexpression of uPAR, which plays a key role in focal adhesion assembly and migration.

Carcinoma, Adenoid Cystic↗
PubMed1985

Adenoid cystic carcinoma of Bartholin's gland: review of the literature and report of two cases.

Two patients with adenoid cystic carcinoma of Bartholin's gland and a review of the relevant literature are presented. With the inclusion of these two patients, there are now 24 cases reported. Both patients had large vulvar masses with a short clinical history, and several local tumor recurrences within the first 21/2 years after radical vulvectomy. The characteristic cribriform pattern and perineural involvement in addition to vascular invasion were present in the pathological material. No metastases were found in the inguino-femoral lymph nodes removed. Both patients are alive, without evidence of local recurrence but with lung metastases. A chemotherapeutic treatment scheme (adriamycin and cyclophosphamide) is underway but it is too early to evaluate its results.

Adult↗
PubMed1989

Adenoid cystic carcinoma of the tracheobronchial tree: clinicopathology and immunohistochemistry.

Adenoid cystic carcinoma of the tracheobronchial tree in five patients was treated surgically and the clinicopathologic manifestations and histogenesis were examined in detail. Symptoms such as cough, dyspnea, hemoptysis, and atelectasis on chest X-ray were present in four patients, and the other patient was asymptomatic. Histologically, growth patterns were classified as tubular, cribriform, and solid. The solid pattern was the most aggressive with extensive perineural invasion. Immunohistochemically, secretory component, lactoferrin, and epithelial membrane antigen were present in the cells lining the gland-like lumen of tissues with the tubular and cribriform patterns, but was rare in those with a solid pattern. Desmin and S-100 protein were detected in the nonlining cells of tissues with all three patterns. These findings suggest that this tumor originates from the myoepithelial cells of the bronchial gland and that the solid pattern was the most poorly differentiated form.

Adult↗
PubMed1993

Argyrophilia in nucleolar organizer regions (AgNOR) in adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma of the salivary glands.

Nine cases of adenoid cystic carcinomas (ACC) and three cases of polymorphous low-grade adenocarcinomas (PLGA) of the salivary glands from the Surgical Oral Pathology Service of the University of São Paulo School of Dentistry were examined by means of the silver-staining nucleolar organizer regions (AgNOR) technique. Quantitative and dimensional analyses of NORs were carried out. Our findings suggest that solid and cribriform patterns of ACC have a higher cellular activity than that presented by tubular ACC and PLGA.

Adenocarcinoma↗
PubMed1995

Nucleolar organizer regions in adenoid cystic carcinoma of the salivary glands.

In this study of proliferative activity of adenoid cystic carcinomas (ACCs) with different histological patterns, the argyrophilic staining method of nucleolar organizer regions (AgNORs) was applied to paraffin sections from 25 tumors. Sixteen of the neoplasms showed a mixture of different histological patterns in the same section. The AgNOR numbers in the different histological pattern areas in the same tissue sections of all 16 tumors were lowest in the cribriform, intermediate in the trabecular, and highest in the solid pattern areas. The mean AgNOR number was highest in the solid pattern (3.33 +/- 0.52), and lowest in the cribriform pattern (2.12 +/- 0.43). The results show the order of proliferative activity in the different histological pattern areas of ACC, and explain the previous clinical finding that the prognosis of ACC is poorest in solid pattern ACCs. AgNOR staining appears to be a useful technique for evaluation of the proliferative activity of each histological pattern area of ACC, especially when there are different histological pattern areas in the same tissue section.

Adult↗
PubMed1990

Epstein-Barr virus infection of epithelial cells derived from primary cultures of adenoidal tissue.

Epithelial cells derived from primary cultures of adenoidal tissue were exposed to Epstein-Barr virus (EBV) from the throat washings of a patient with infectious mononucleosis (IM) and P3HR-1 and B95-8 cell strains. They were then examined for EBV-specific antigens by immunofluorescence. EBV from both the P3HR-1 cell strains and the throat washings of the IM patient infected the epithelial cells at the 6th and 9th days, respectively. Although the EBV-antigen-positive cells did not increase in number and disappeared at the 12th day after infection, EBV antigens of the virus's replication cycle could still be detected in the epithelial cells shed from cell culture layer at this time. However, the virus obtained from the cell-free 12th day's culture medium was incapable of transforming cord blood lymphocytes.

Adenoids↗
PubMed1995

Biosynthesis of basement membrane molecules by salivary adenoid cystic carcinoma cells: an immunofluorescence and confocal microscopic study.

The biosynthesis of basement membrane molecules and fibronectin was studied in vitro in the two different human cell systems (ACC2 and ACC3) established from adenoid cystic carcinomas (ACC) of the salivary gland using immunofluorescence and confocal microscopy. When cells were attached and spread on dishes, fine granular immunofluorescence for type IV collagen, laminin, heparan sulphate proteoglycan, entactin, and fibronectin first appeared diffusely in the cytoplasm, and then changed in aggregation of coarse granules in the perinuclear area. With formation of colonies, these signals were present in the extracellular space, initially in the basal aspect of attached cells and consequently in the lateral intercellular space. After the cells formed a confluent monolayer, extracellular signals started to decrease in inverse proportion to the reappearance of intracellular ones. The results indicate that the parenchymal cells of ACC synthesize these five extracellular matrix molecules, secrete them into the extracellular milieu and remodel the extracellular deposits. It is suggested that the characteristic stromal architecture of ACC, represented by stromal pseudocysts, results from their own secretion of the basement membrane molecules and fibronectin.

Adult↗