A mechanistic basis for the malignant progression of salivary gland tumors.
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ABSTRACT:
SUBMITTER: Taniguchi S
PROVIDER: S-EPMC8661530 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The purpose of this study was to define the proteome profile of fine needle aspiration (FNA) samples of malignant major salivary gland tumors (MSGT) compared to benign counterparts, and to evaluate potential clinical correlations and future applications. Patients affected by MSGT (n?=?20), pleomorphic adenoma (PA) (n?=?37) and Warthin's tumor (WT) (n?=?14) were enrolled. Demographic, clinical and histopathological data were registered for all patients. FNA samples were processed to obtain the protein extracts. Protein separation was obtained by two-dimensional electrophoresis (2-DE) and proteins were identified by mass spectrometry. Western blot analysis was performed to validate the 2-DE results. Statistical differences between groups were calculated by the Mann-Whitney U test for non-normal data. Spearman's rank correlation coefficient was calculated to evaluate correlations among suggested protein biomarkers and clinical parameters. Twelve and 27 differentially expressed spots were found for MSGT versus PA and MSGT versus WT, respectively. Among these, annexin-5, cofilin-1, peptidyl-prolyl-cis-trans-isomerase-A and F-actin-capping-alpha-1 were able to differentiate MSGT from PA, WT, and healthy samples. Moreover, STRING analysis suggested cofilin-1 as a key node of protein interactions. Some of the overexpressed proteins are related to some clinical factors of our cohort, such as survival and outcome. Our results suggest potential protein biomarkers of MSGT, which could allow for more appropriate treatment plans, as well as shedding light on the molecular pathways involved.
| S-EPMC7235111 | biostudies-literature
Project description:Salivary gland carcinomas (SGCs) represent a group of rare tumors, with complete surgical resection being the main treatment option. Therapeutic armory for cases of locally aggressive, recurrent, and/or metastatic SGCs, though, remains poor since they exhibit high rates of resistance to systematic therapy. Angiogenesis is considered one of the contemporary hallmarks of cancer and anti-angiogenic factors have already been approved for the treatment of several cancer types. This review aims to summarize, in a histotype-specific manner, the most current available data on the angiogenic factors implicated in SGC angiogenesis, in order to highlight the differences between the most common SGC histotypes and the factors that may have a potential role as therapeutic targets.
| S-EPMC7762607 | biostudies-literature
Project description:With the advent of targeted therapies, expression of sex hormone receptors and HER-2 in salivary gland tumors (SGTs) is of clinical interest. Previous reports of estrogen (ER) and progesterone (PR) receptor expression have varied. Androgen receptor (AR) and HER-2 overexpression are frequently reported in salivary duct carcinoma (SDC), but have not been studied systematically in other SGTs. This study examines ER, PR, AR, and HER-2 expression in SGTs. Immunohistochemistry for ER, PR, AR, and HER-2 was performed on 254 SGTs (134 malignant). ER, PR, and AR expression was scored using Allred system. HER-2 expression was scored using Dako HercepTest guidelines. FISH for HER-2 amplification was performed on select cases with HER-2 overexpression (2-3+). No SGT demonstrated strong expression of ER or PR. Combined strong AR and HER-2 expression was seen in 22 carcinomas: 14/25 SDC, 3/16 poorly differentiated, two oncocytic, and one each carcinoma ex pleomorphic adenoma, squamous cell, and intraductal carcinoma. Eighteen additional high grade carcinomas had HER-2 overexpression with absent, weak, or moderate AR expression; eight high grade carcinomas had isolated strong AR expression with 0-1+?HER-2 staining. Of 15 tested cases, six demonstrated HER-2 amplification by FISH, all of which had 3+?immunoreactivity. Neither benign nor malignant SGTs had strong expression of ER or PR. None of the benign SGTs overexpressed AR or HER-2. Coexpression of AR and HER-2 should not define SDC, but immunostaining should be considered in high grade salivary carcinomas, as some show overexpression and may benefit from targeted therapy.
| S-EPMC5873488 | biostudies-literature
Project description:The role of sex hormone receptors in human cancer development and progression has been well documented in numerous studies, as has the success of sex hormone antagonists in the biological therapy of many human tumors. In salivary gland tumors (SGTs), little and conflicting information about the role of the estrogen receptor alpha (ER?), progesterone receptor (PgR) and androgen receptor (AR) has been described and in most cases the use of sex hormone antagonists is not contemplated in clinical practice. In this study, we analyzed a panel of sex hormone receptors that have not been widely investigated in SGTs-ER?, PgR, AR, but also ER? and GPR30-to define their expression pattern and their prognostic and predictive value in a case series of 69 benign and malignant SGTs. We showed the aberrant expression of AR in mucoepidermoid and oncocytic carcinoma, a strong relation between cytoplasmic ER? expression and tumor grade, and a strong correlation between nuclear GPR30 expression and disease-free survival (DFS) of SGT patients.
| S-EPMC5855621 | biostudies-literature
Project description:Effective treatment options for advanced salivary gland tumors are lacking. To better understand these tumors, we report their genomic landscape. We studied the molecular aberrations in 117 patients with salivary gland tumors that were, on physician request, tested in a Clinical Laboratory Improvement Amendments (CLIA) laboratory (Foundation Medicine, Cambridge, MA) using next-generation sequencing (182 or 236 genes), and analyzed by N-of-One, Inc. (Lexington, MA). There were 354 total aberrations, with 240 distinct aberrations identified in this patient population. Only 10 individuals (8.5%) had a molecular portfolio that was identical to any other patient (with four different portfolios amongst the ten patients). The most common abnormalities involved the TP53 gene (36/117 [30.8% of patients]), cyclin pathway (CCND1, CDK4/6 or CDKN2A/B) (31/117 [26.5%]) and PI3K pathway (PIK3CA, PIK3R1, PTEN or AKT1/3) (28/117 [23.9%]). In multivariate analysis, statistically significant co-existing aberrations were observed as follows: TP53 and ERBB2 (p = 0.01), cyclin pathway and MDM2 (p = 0.03), and PI3K pathway and HRAS (p = 0.0001). We were able to identify possible cognate targeted therapies in most of the patients (107/117 [91.5%]), including FDA-approved drugs in 80/117 [68.4%]. In conclusion, salivary gland tumors were characterized by multiple distinct aberrations that mostly differed from patient to patient. Significant associations between aberrations in TP53 and ERBB2, the cyclin pathway and MDM2, and HRAS and the PI3K pathway were identified. Most patients had actionable alterations. These results provide a framework for tailored combinations of matched therapies.
| S-EPMC4694855 | biostudies-other
Project description:PurposeThe clinical practice of elastosonography for the detection of salivary gland tumors is still a controversial issue. The objective of this meta-analysis was to evaluate the effect of elastosonography for the diagnosis of salivary gland tumors and to compare the diagnostic value of elastosonography and conventional ultrasound in the diagnosis of salivary gland tumors.MethodsA comprehensive literature search through PubMed, EMBASE, and Cochrane Library was carried out from inception to November 2021. Two researchers independently extracted the data from the enrolled papers using a standard data extraction form. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated to evaluate the diagnostic performance of elastosonography. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was utilized to evaluate the quality of each included study. Meta-DiSc version 1.4, Review Manager 5.3, and StataSE 15 were used.ResultsSixteen studies with a total of 1105 patients with 1146 lesions were included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR of elastosonography for the differentiation between benign and malignant salivary gland tumors were 0.73 (95%CI, 0.66-0.78), 0.64 (95%CI, 0.61-0.67), 2.83 (95%CI, 1.97-4.07), 0.45 (95%CI, 0.32-0.62), and 9.86 (95%CI, 4.49-21.62), respectively, with an AUC of 0.82. Four studies provided data regarding the conventional ultrasound for the differentiation between benign and malignant salivary gland tumors. The pooled sensitivity, specificity, and DOR were 0.62 (95%CI, 0.50-0.73), 0.93 (95%CI, 0.90-0.96), and 25.07 (95%CI, 4.28-146.65), respectively. The meta-regression and subgroup analyses found that assessment methods were associated with significant heterogeneity, and quantitative or semiquantitative elastosonography performed better than the qualitative one.ConclusionsElastosonography showed a limited value for diagnosing malignant salivary gland tumors; it could be considered as a supplementary diagnostic technology to conventional ultrasound, and quantitative or semiquantitative elastosonography was superior to the qualitative one.
| S-EPMC9533713 | biostudies-literature
Project description:Malignant tumors affecting minor salivary glands present a wide range of histopathologic types. The present study sought to design a protocol for management of patients with malignancy of minor salivary glands. The data of 22 patients with malignant tumors of the minor salivary glands, surgically treated at our department in the past 10 years, were accumulated and studied. All patients underwent a diagnostic workup prior to surgery. The most useful examinations were magnetic resonance imaging of the head and neck and computerized tomography of the thorax. Wide local excision was sufficient for the majority of patients. Adjuvant treatment is indicated for high-grade, tumor-positive lymph nodes and residual disease. Malignant tumors of minor salivary glands are very rare. Therefore, design of management protocols is challenging. Management of the neck is necessary in evidence of metastasis and in high-grade and advanced-stage disease. Adjuvant treatment should be included in the treatment protocol in certain indications. Most importantly, long-term follow up is very important for all patients with malignant minor salivary tumors.
| S-EPMC3208333 | biostudies-other
Project description:Salivary gland tumors comprise a group of 24 tumor subtypes with a wide range of clinical behaviors and propensities for metastasis. Several prognostic factors have been identified that help predict the development of systemic metastases, most commonly to the lung, liver, or bone. Metastases to the brain are rare. To better understand the behavior of salivary gland tumors that metastasise to the brain, we performed a retrospective cohort analysis on a series of patients to highlight features of their medical and surgical management. From 2007 to 2011, a database of 4117 elective craniotomies were queried at a single institution to identify patients surgically treated for salivary gland metastases to the brain. Three patients were identified. Histologic subtypes included salivary duct carcinoma, poorly differentiated carcinoma, and papillary mucinous adenocarcinoma. They had all undergone previous treatment for their primary malignancy. The mean time to intracranial metastasis was 48 months from initial diagnosis (range, 14-91 months). Treatment for intracranial metastases included surgical resection, whole brain radiation, stereotactic radiosurgery, and chemotherapy. Intracranial metastases from salivary gland tumors are rare, present years after diagnosis of the primary tumor, and are treatable with multimodality therapy.
| S-EPMC3749258 | biostudies-literature
Project description:Supposed risk of malignant transformation of salivary gland pleomorphic adenoma (SGPA) is an important reason for aggressive retreatment in recurrent pleomorphic adenoma (RPA). However, although the diagnostic category 'carcinoma ex-pleomorphic adenoma' suggests that malignant transformation of a pleomorphic adenoma is a regular event, this has to date not been shown to occur in sequential lesions of one patient. Here, we show the molecular events in transformation to malignancy of a pleomorphic adenoma of the parotid gland. Detailed molecular analysis revealed an LIFR/PLAG1 translocation characteristic for pleomorphic adenoma and, next to this, a PIK3R1 frameshift mutation and several allelic imbalances. In subsequent malignant recurrences, the same LIFR/PLAG1 translocation, PIK3R1 frameshift mutation, and allelic imbalances were present in addition to TP53 mutations. Thus, this case not only shows malignant transformation of SGPA, but also demonstrates that molecular analysis can be of help in recognising malignancy in the rare instance of RPA.
| S-EPMC8363925 | biostudies-literature
Project description:Salivary gland tumors (SGTs) of parotid origin are a group of diverse neoplasms which are difficult to classify due to their rarity and similar morphologic patterns. Chromosome analysis can detect clonal abnormalities, and array comparative genomic hybridization (aCGH) analysis can define copy number alterations (CNAs) from tumor specimens. Of the 19 cases of various types of SGTs submitted for cytogenomic analyses, an abnormal clone was detected in nine cases (47%), and CNAs were detected in 14 cases (74%). Recurrent rearrangements involving the PLAG1 gene at 8q12, recurrent CNAs including deletions of 6q, 9p (CDKN2A), and 17p (TP53), loss of Y chromosome, and gain of chromosome 7 were defined from these cases. Combined karyotyping and aCGH analyses could improve diagnostic yield. Future study for more precisive correlation of SGT classification with cytogenomic abnormalities will facilitate better diagnosis and treatment.
| S-EPMC7725583 | biostudies-literature