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A 10-year review of primary major salivary gland cancers.

ABSTRACT: Primary salivary gland cancers comprise a heterogeneous group of histological entities and represent less than 5% of head and neck malignancies. Surgical resection is the main treatment, and adjuvant radiotherapy is performed in selected cases. Chemotherapy is an option in metastatic or recurrent disease, with poor evidence. We aimed to review a 10-year experience of a cancer centre on major salivary gland cancers, focusing on clinical, pathological, treatment and patients' outcomes data. A total of 93 patients were identified, median age at diagnosis was 64 years (IQR, 23), and 51.6% were male. The parotid gland was the site of origin in 76.3% of cases. The most frequent histological type was salivary duct carcinoma (21.5%). All patients were submitted to surgery and adjuvant radiotherapy was performed in 74.2%. From 26 patients diagnosed with metastatic disease, 9 were treated with systemic therapy. At 8 years, disease-free survival was 54.6% and overall survival was 48.4%. Male sex, salivary duct carcinoma, stage pT3-4, stage pN2-3, high histologic grade, lymphovascular invasion and perineural invasion were negative prognostic indicators for disease-free survival and overall survival. Extracapsular spread was a negative prognostic indicator for overall survival. In the multivariable analysis, histological type-salivary duct carcinoma-kept significant negative impact in disease-free survival and high histologic grade in overall survival. The most frequent histological type was salivary duct carcinoma, which is estimated to represent only 9% of salivary tumours. Patients with salivary duct carcinoma relapsed more than other histological types. High histologic grade was a negative prognostic indicator for overall survival.

SUBMITTER: Cruz A

PROVIDER: S-EPMC7302884 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A 10-year review of primary major salivary gland cancers.

Cruz Andreia A Magalhães Helena H Pereira Filipa Ferreira FF Dinis José J Vieira Cláudia C

Ecancermedicalscience 20200612

Primary salivary gland cancers comprise a heterogeneous group of histological entities and represent less than 5% of head and neck malignancies. Surgical resection is the main treatment, and adjuvant radiotherapy is performed in selected cases. Chemotherapy is an option in metastatic or recurrent disease, with poor evidence. We aimed to review a 10-year experience of a cancer centre on major salivary gland cancers, focusing on clinical, pathological, treatment and patients' outcomes data. A tota ...[more]

PMID: 32582370

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Project description:BackgroundAntibody responses against Anopheles salivary proteins can indicate individual exposure to bites of malaria vectors. The extent to which these salivary proteins are species-specific is not entirely resolved. Thus, a better knowledge of the diversity among salivary protein repertoires from various malaria vector species is necessary to select relevant genus-, subgenus- and/or species-specific salivary antigens. Such antigens could be used for quantitative (mosquito density) and qualitative (mosquito species) immunological evaluation of malaria vectors/host contact. In this study, salivary gland protein repertoires (sialomes) from several Anopheles species were compared using in silico analysis and proteomics. The antigenic diversity of salivary gland proteins among different Anopheles species was also examined.ResultsIn silico analysis of secreted salivary gland protein sequences retrieved from an NCBInr database of six Anopheles species belonging to the Cellia subgenus (An. gambiae, An. arabiensis, An. stephensi and An. funestus) and Nyssorhynchus subgenus (An. albimanus and An. darlingi) displayed a higher degree of similarity compared to salivary proteins from closely related Anopheles species. Additionally, computational hierarchical clustering allowed identification of genus-, subgenus- and species-specific salivary proteins. Proteomic and immunoblot analyses performed on salivary gland extracts from four Anopheles species (An. gambiae, An. arabiensis, An. stephensi and An. albimanus) indicated that heterogeneity of the salivary proteome and antigenic proteins was lower among closely related anopheline species and increased with phylogenetic distance.ConclusionThis is the first report on the diversity of the salivary protein repertoire among species from the Anopheles genus at the protein level. This work demonstrates that a molecular diversity is exhibited among salivary proteins from closely related species despite their common pharmacological activities. The involvement of these proteins as antigenic candidates for genus-, subgenus- or species-specific immunological evaluation of individual exposure to Anopheles bites is discussed.

Project description:BackgroundAlthough high-grade salivary gland cancers (SGCs) often express androgen receptor (AR) and/or HER-2/neu, therapeutically targeting these receptors in SGC remains investigational. We investigated the prevalence of receptor expression and the benefit of adjuvant HER-2 directed therapy in the high-risk postoperative setting and explored the clinical utility of sequentially targeting these receptors in the setting of advanced disease.Materials and methodsWe clinically annotated 95 patients with SGC (excluding adenoid cystic carcinoma) treated at our institution from 2002 to 2019 and recorded AR, HER-2/neu status, and tumor genomic profiling results when available. Clinicopathologic information was then integrated with outcomes.ResultsOf 95 patients, most had high-risk histologies, with salivary duct carcinoma (SDC) as the most frequent diagnosis (43, 45%). Thirty-five (37%) experienced recurrence (51% SDC). HER-2/neu was positive (1-3+) by immunostaining in 34 of 52 (65%) evaluable cases. There was no difference in survival based on HER-2/neu or AR expression. Nine of 17 (53%) patients with HER-2+ SDC received adjuvant chemoradiation with trastuzumab. Median disease-free survival (DFS) and overall survival (OS) were longer among patients with HER-2/neu 3+ staining tumors who received adjuvant trastuzumab versus those who did not (DFS, 117 vs. 9 months; p = .02; OS, 74 vs. 43 months; p = .02), with no difference among other HER-2/neu subgroups (0-2+). Two of nine (22%) patients treated with adjuvant trastuzumab demonstrated recurrence, both with low HER-2/neu staining intensity (1+). Longer time to recurrence (hazard ratio, 0.94; p = .01) predicted improved outcomes. Both androgen deprivation and HER-2-directed therapies had clinical benefit beyond the first-line metastatic setting, with partial response observed beyond second-line use.ConclusionAlthough prospective data are lacking, the use of adjuvant trastuzumab in high-risk patients with SGC appears beneficial, particularly among patients with tumors exhibiting HER-2/neu 3+ immunostaining.Implications for practiceResults of this study showed an improved disease-free and overall survival in patients treated with adjuvant trastuzumab for high-risk salivary gland cancers with strong HER-2/neu staining intensity. Following recurrence or metastatic spread, sequential HER-2, and androgen-directed therapies may benefit certain patients with salivary gland cancer.

Project description:ObjectiveA major characteristic of the autoimmune disease primary Sjögren's syndrome (SS) is salivary gland (SG) hypofunction. The inability of resident SG stem cells (SGSCs) to maintain homeostasis and saliva production has never been explained and limits our comprehension of mechanisms underlying primary SS. The present study was undertaken to investigate the role of salivary gland stem cells in hyposalivation in primary SS.MethodsSGSCs were isolated from parotid biopsy samples from controls and patients classified as having primary SS or incomplete primary SS, according to the American College of Rheumatology/European League Against Rheumatism criteria. Self-renewal and differentiation assays were used to determine SGSC regenerative potential, RNA was extracted for sequencing analysis, single telomere length analysis was conducted to determine telomere length, and frozen tissue samples were used for immunohistochemical analysis.ResultsSGSCs isolated from primary SS parotid gland biopsy samples were regeneratively inferior to healthy control specimens. We demonstrated that SGSCs from samples from patients with primary SS are not only lower in number and less able to differentiate, but are likely to be senescent, as revealed by telomere length analysis, RNA sequencing, and immunostaining. We further found that SGSCs exposed to primary SS-associated proinflammatory cytokines we induced to proliferate, express senescence-associated genes, and subsequently differentiate into intercalated duct cells. We also localized p16+ senescent cells to the intercalated ducts in primary SS SG tissue, suggesting a block in SGSC differentiation into acinar cells.ConclusionThis study represents the first characterization of SGSCs in primary SS, and also the first demonstration of a linkage between an autoimmune disease and a parenchymal premature-aging phenotype. The knowledge garnered in this study indicates that disease-modifying antirheumatic drugs used to treat primary SS are not likely to restore saliva production, and should be supplemented with fresh SGSCs to recover saliva production.

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A 10-year review of primary major salivary gland cancers.

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A 10-year review of primary major salivary gland cancers.

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