Cystic Carcinoma Of Salivary Glands Research Articles

Evaluation of Immunohistochemical Expression of P53 and Pcna in Pleomorphic Adenoma, Mucoepidermoid and Adenoid Cystic Carcinomas of Salivary Glands

Salivary gland tumours are uncommon with a broad heterogeneity. The most common benign tumour is the pleomorphic adenoma, whereas mucoepider moid carcinoma and adenoid cystic carcinoma predominate among the malignancies. The aim of this study was to describe the tissue expression of p53 and PCNA protein in pleomorphic adenoma, mucoepidermoid carcinoma and adenoid cystic carcinoma and to compare their expression among the studied tumors. The study enrolled (45)formalin –fixed, paraffin- embedded tissue blocks of salivary gland tumors, diagnosed as pleomorphic adenoma, mucoepidermoid carcinoma and adenoid cystic carcinoma (15 cases for each ) and evaluated the immunohistochemical expression of P53 and PCNA proteins. The study revealed positive p53 protein expression in (60%) of muocoepidermoid carcinoma cases and (20%) of adenoid cystic carcinoma cases, while only one case (6.7%) of pleomorphic adenoma was P53 posi tive. The immunopositivity of PCNA protein expression was f ound in (100%) of both mucoepidermoid carcinoma and adenoid cystic carcinoma cases and (66.7%) of pleomorphic adenoma c ases.The results of this study demonstrated that inactivation of p53 protein may play an im portant role in the activation of PCNA with increasing the proliferati on activity of MEC and ACC.

Post-operative radiotherapy in adenoid cystic carcinoma of salivary glands versus surgery alone: what is the evidence about survival and local control? A systematic review and meta-analysis.

Adenoid cystic carcinoma of the salivary glands is a relatively rare malignancy characterized by slow growth and a poor prognosis, and effective treatments remain challenging to identify. This systematic review, following the PRISMA guidelines, aimed to analyze the potential benefits of post-operative radiotherapy in terms of local control of recurrences and survival advantages when compared with surgery alone in patients with adenoid cystic carcinoma. A comprehensive systematic review was conducted by searching the MEDLINE, Cochrane, EMBASE, and OVID databases from January 1999 to July 2022. The goal was to identify articles comparing surgery alone with surgery plus postoperative radiotherapy for adenoid cystic carcinoma of the salivary glands. Downs and Black Checklist was used to assess the methodological quality and risk of bias of each included study. The data analysis was performed using Review Manager version 5.4.1. This review included 8 studies comprising a total of 3103 patients, divided based on the analyzed outcomes. The pooled odds ratio for overall survival at 5years was 0.87 (95% confidence interval 0.43-1.76, p = 0.70), and at 10years was 1.23 (95% confidence interval 0.69-2.16, p = 0.48). In both cases, no statistically significant differences were observed. However, the pooled odds ratio for local control at 5years was 3.37 (95% confidence interval 1.35-8.42, p = 0.009), providing strong support for the use of post-operative radiation. The findings from the meta-analysis suggest that post-operative radiotherapy significantly improves local control in patients with adenoid cystic carcinoma. However, there was no statistically significant increase in survival at 5 and 10years. It is essential to note that the quality of the studies included in this meta-analysis ranged from fair to poor. To better clarify the indications for post-operative radiotherapy, future high-quality research is needed, particularly with improved stratification of patient groups. Additionally, it is important to recognize that achieving local control in adenoid cystic carcinoma is crucial for enhancing the overall quality of life for patients. We acknowledge that this review was not registered in the PROSPERO database, and the data pooling was conducted using a random effects model.

Adenoid Cystic Carcinoma of Salivary Glands: A Ten-Year Review and an Assessment of the Current Management, Surgery, Radiotherapy, and Chemotherapy.

Adenoid cystic carcinoma (ACC) is a rare cancer that arises from the salivary glands and other sites in the body, such as the lung and breast. Although the tumor accounts for 10% of all salivary gland malignancies, it only accounts for 1% of head and neck malignancies. It can affect both major and minor salivary glands; here, it is called salivary gland adenoid cystic carcinoma or SACC, with a slight predilection to the latter, and commonly manifests between the 6th and 7th decades of life. The disease also shows a slight female predilection, with a reported female to male ratio of 3 : 2. Lesions of SACC are often insidious and slow-growing, and symptoms such as pain and altered sensation are frequently associated with advanced stages of the disease. Salivary adenoid cystic carcinoma is characterized by perineural invasion (PNI), a distinctive feature that potentially plays a significant role in the tumor's relapse and recurrence, which is approximately 50%. The disease is not prevalent, and its etiopathogenesis is poorly understood, although several genetic patterns and biomarkers have been linked to its initiation and/or progression. The discovery of these mutations and biomarkers has encouraged several clinical studies to use therapeutic agents to target the specific receptors on the cancer cells to potentially prevent further proliferation of the tumor cells and metastasis of the disease. Diagnosis of SACC is often challenging and frequently requires a combination of clinical examination, imaging, and histopathology. Management of SACC is primarily surgical excision, while radiotherapy has shown to be effective in improving local control in cases with microscopic residual disease. However, treatment of recurrent or metastatic tumors by radiotherapy with or without chemotherapy has so far shown limited success. The aim of this thesis is to provide an update of literature on SACC with a particular focus on the latest management approaches and future trends.

Abstract 4897: PRT543, a methyl transferase inhibitor, has potent anti-tumor activity against adenoid cystic carcinoma of salivary glands

Abstract Adenoid Cystic Carcinoma (ACC) is a rare but aggressive malignancy of salivary gland, associated with protracted clinical course and fatal outcome. Treatment modalities are restricted to surgery and/or adjuvant radiotherapy and patients develop recurrence and distant metastasis over time. The absence of effective systematic therapy makes it incurable in advanced stage. ACC display an overall low mutation frequency, therefore very few actionable genetic alterations critical to the ACC development have been recognized. MYB fusion/overexpression is the most frequently found genetic alteration in ACC and is present in ~70% patients. This is followed by activating NOTCH mutations, reported in ~20% patients. Despite the presence of few targetable genetic alterations, recent studies revealed substantial transcriptomic heterogeneity amongst ACC tumors suggesting the role of epigenetic alterations in ACC oncogenesis. Symmetric dimethylation is an important epigenetic mechanism that regulates mRNA splicing, transcription, translation, cell cycle and oncogenic signaling pathways. Protein Arginine Methyl Transferase 5 (PRMT5) is a predominant enzyme for symmetric dimethylation among a family of 9 methyl transferases. In was suggested that PRMT5 plays a role in regulating tumor progression via modulation of MYC signaling, cancer stemness, and a wide array of additional cellular and transcriptional pro-oncogenic processes. While inhibition of PRMTs showed anti-oncogenic response in several preclinical tumor models and a subset of patients with advanced solid malignancies (including ACC), preclinical studies investigating the effect of PRMT5 blockade in ACC remain inadequate. In part, due to the scarcity of ACC specimens and limited availability of the experimental models. PRT543 is a selective and potent small molecule PRMT5 inhibitor that specifically targets PRMT5 among 37 methyl transferases. In the present study, we have investigated the effect this novel agent using a unique collection of ACC cell lines, organoids, and patient derived xenograft mouse models. To our knowledge, this is the first study investigating the therapeutic effect of PRT543 in several preclinical models of ACC. Specifically, we found that PRT543 has potent antitumor activity in in-vitro and in-vivo models with MYB expression and activating NOTCH mutations. Further, based on these observations, we have sequenced a collection of 50 ACC tumor samples to identify the subset of patients who may potentially benefit from PRT543 treatment based on their underlying genetic signatures. This study provides evidence underscoring the role of PRMT5 signaling in ACC and supports the clinical development of PRMT5 inhibitors for this indication. Citation Format: Vasudha Mishra, Alka Singh, Xiangying Chen, Michael Korzinkin, Claudia Wing, Viktoria Sarkisova, Alexandra Ozerova, Oksana Glushchenko, Venkat Thodima, Koichi Ito, Peggy Scherle, Mark Lingen, Rifat Hasina, Alexander Pearson, Ari Rosenberg, Alex Zhavoronkov, Bruce Ruggeri, Nishant Agrawal, Evgeny Izumchenko. PRT543, a methyl transferase inhibitor, has potent anti-tumor activity against adenoid cystic carcinoma of salivary glands. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4897.

Neoadjuvant Chemotherapy as a Viable Treatment Option for Locally Advanced Adenoid Cystic Carcinoma of Salivary Gland: a Case Report

Adenoid cystic carcinoma (ACC) is a rare infiltrative tumor predominantly affecting minor salivary gland along with submandibular and parotid glands. Its biological behavior has not been clearly understood, and only few researches have been performed regarding treatment options. Patient usually presents with swelling of salivary gland region with complaints of paresthesia, numbness, and pain or muscle weakness due to nerve involvement. Diagnosis is confirmed on histopathology, and surgical excision is the treatment of choice in resectable cases. The role of neoadjuvant chemotherapy or radiotherapy remains debatable in advanced presentation. Present case depicts the role of chemotherapy and radical surgery in its management. Here, we present a case of recurrent locally advanced ACC that was down staged and underwent R0 resection after neoadjuvant chemotherapy (NACT). After two and half years of follow-up, the patient is alive and disease-free. Adenoid cystic carcinoma (ACC) is a rare and aggressive variant of salivary gland neoplasm. Perineural invasion and resistance to present chemotherapeutic drugs makes treatment more challenging. Role of chemotherapy remains controversial and in upfront technically unresectable cases neoadjuvant chemotherapy (NACT) can be used as an option to achieve R0 resection.

Analysis of Cytological Misdiagnosis and Oversight of Adenoid Cystic Carcinoma of Salivary Gland.

In this article on adenoid cystic carcinoma (ACC) of salivary gland, we intend to summarize the causes of misdiagnosis and oversight of ACC hoping to improve cytological diagnostic accuracy, clinical management and patient treatment. The study retrospectively reviewed 32 patients with ACC of salivary gland, registered at the Affiliated Hospital of Southwest Medical University from July 2014 to June 2021. These cases were diagnosed by FNA and surgical excision biopsy. All cytopathological results were retrospectively categorized according to Milan system for reporting salivary gland cytopathology (MSRSGC). The accuracy of FNA was verified by surgical excision biopsy. Of these 32 patients, 16 (50.0%) cases were male, and 16 (50.0%) were female. Their age ranged from 21 to 79 years, with an average age of 50.32 years. The highest incidence (15/32, 46.9%) of ACC was observed in patients between 41 and 50 years of age. 10 cases (31.3%) occurred in the parotid gland, 9 cases (28.1%) in the submandibular gland, 9 cases (28.1%) in the sublingual gland, 3 cases (9.4%) in the palate, and 1 case (3.1%) in the lip. Among the 32 cases of ACC, 23 cases (71.9%) were classified to VI, 4 cases (12.5%) to IVa, and 5 cases (15.6%) to II by MSRSGC. A comparison of the FNA results with biopsy showed that the accuracy of FNA in ACC of salivary gland is 71.9%. Being able to identify the cytomorphological features is the key factor for accurate diagnosis of ACC of the salivary gland. Our results confirm that FNA is an important initial screening in the diagnosis of ACC of salivary gland. Increased study of the cytomorphology of ACC is beneficial for more accurate diagnosis of ACC, to reduce misdiagnosis and oversight.

Metastatic Adenoid Cystic Carcinoma of Salivary Gland: A Case Report and Review of Literature

Metastatic Adenoid Cystic Carcinoma of Salivary Gland: A Case Report and Review of Literature

CALCB rs3829222 T/T Genotype and Low Expression of CALCB Are High-Risk Factors for Adenoid Cystic Carcinoma of Salivary Gland.

Objectives To investigate the relationship between polymorphisms of calcitonin-related peptide gene II (beta-calcitonin gene-related peptide (βCGRP), CALCB) and serum CGRP levels in salivary adenoid cystic carcinoma. Materials and Methods Using the polymerase chain reaction (PCR) technique, the full-length amplification and genotype analysis of CALCB genes were performed in 39 patients with adenoid cystic carcinoma of salivary gland and 158 normal controls. The gene frequencies of major genotype of CALCB in adenoid cystic carcinoma of salivary gland and normal control group were analyzed. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate serum calcitonin gene-related peptide (CGRP) and its concentration of alpha and beta subtypes. Results Univariate logistic regression analysis showed that the CALCB rs2839222 T/T genotype was closely related to the occurrence of salivary adenoid cystic carcinoma, with a correlation coefficient of 3.89. Conclusions The serum CGRP concentration in the salivary adenoid cystic carcinoma group was 1.56 times that of the normal control group. The αCGRP subtype was significant, which was 3.02 times that of the normal control. The polymorphism of βCGRP gene is associated with genetic susceptibility to salivary adenoid cystic carcinoma, and serum CGRP and βCGRP can be used as novel markers of salivary adenoid cystic carcinoma.

Adenoid Cystic Carcinoma of Salivary Glands – A Duplet of Cases

Adenoid Cystic Carcinoma of Salivary Glands – A Duplet of Cases

Comparative Analysis of P63, Maspin and Matrix Metalloproteinase 2 Expression in Mucoepidermoid Carcinoma and Adenoid Cystic Carcinoma of Salivary Glands.

Statement of the Problem: The tumor suppressor role of myoepithelial cells and related mechanisms in breast tumors are well understood. However, the role of these cells in tumors of salivary glands is debatable.Purpose: The present study was designed to determine the expression of p63, mammary serine protease inhibitor (maspin) and matrix metalloproteinase 2 (MMP-2) in mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ADCC) of salivary glands due to various cellular differentiation and structure. The association between the expression of these markers and clinicopathologic features and myoepithelial differentiation were also evaluated.Materials and Method: P63, maspin, and MMP-2 expression were immunohistochemically studied in 67 cases including35 cases of MEC and 32 cases of ADCC. The smooth muscle actin (SMA) staining was also applied to confirm the presence of myoepithelial differentiation. Data was analyzed using Chi-square test, Mann-Whitney U test and t-test.Results: The expression of p63 (p= 0.009) and maspin (p= 0.012) significantly differed between the study groups. P63 positive cells in MEC were negative for SMA staining in contrast to ADCC. Furthermore, the expression of P63 (p= 0.045) and maspin (p= 0.019) significantly and inversely correlated with histologic grade in ADCC. Likewise, positive significant correlation was detected between histologic grade and expression of P63 (p= 0.018) and MMP-2 (p= 0.003) in MEC samples.Conclusion: Our findings showed that MEC is devoid of myoepithelial cells. The difference in expression of P63 and maspin in ADCC and MEC highlighted the role and presence of myoepithelial cells in ADCC. Indeed, the high expression of P63 and maspin in well-differentiated ADCCs suggests the tumor suppressor effect of myoepithelial cells. Considering the association between the evaluated markers and histological grade, p63 in both tumors, maspin in ADCC and MMP-2 in MEC may be efficient predictors of clinical behavior.

Clinicopathological features of lung salivary gland-type tumors

Objective: To study the clinicopathological characteristics of lung salivary gland-type tumors (SGT), and to compare with the corresponding primary SGT in salivary glands. Methods: Twenty-three cases of lung SGT were retrieved from the files of Peking University First Hospital from January 2004 to September 2018. The morphology, immunophenotype, genotype and outcome of these cases were analyzed. Results: The 23 patients included 13 males and 10 females, with age range of 13-79 years (median 54 years). There were 11 cases of adenoid cystic carcinoma, 10 cases of mucoepidermoid carcinoma (MEC), one case each of clear cell carcinoma and myoepithelioma. The morphology and immunophenotype of lung SGT were very similar to their counterparts in salivary gland. MYB rearrangement was detected in one of 11 adenoid cystic carcinomas. MAML2 rearrangement was detected in all the MECs. EWSR1 rearrangement was detected in the one case of clear cell carcinoma. Of patients with adenoid cystic carcinoma, the survival time was more than 60 months (three cases), 52 months (one case), and 12-36 months (three cases). There was no recurrence and death in seven cases of MEC with follow-up results. One case of clear cell carcinoma recurred after 52 months of follow-up. Conclusions: Although the SGT of lung and their counterparts in salivary gland are very similar in their morphology, immunophenotype, genotype and prognosis, there are also some differences between each other. MYB rearrangement can be detected in most adenoid cystic carcinomas of salivary gland, but rarely in lung adenoid cystic carcinoma. The prognosis of patients with lung MEC is better than that of patients with salivary gland MEC, while the prognosis of patients with lung adenoid cystic carcinoma is worse than that of patients with salivary gland adenoid cystic carcinoma.

Kallikrein-Related Peptidase mRNA Expression in Adenoid Cystic Carcinoma of Salivary Glands: A Polymerase Chain Reaction Study

Kallikrein-related peptidases (KLKs) are a group of 15 serine proteases implicated in a variety of biological processes. Aberrant expression of KLKs has been associated with the development of certain cancers. However, the role of KLKs in salivary tumors has not been extensively studied. This study evaluated the expression of KLKs in both adenoid cystic carcinoma (ACC) and normal salivary gland tissue. We isolated total RNA from 39 formalin-fixed, paraffin-embedded samples, which included 24 ACCs and 15 normal salivary gland tissues. Complementary DNA, synthesized by reverse transcription, was combined with gene specific kallikrein primers (KLK1-KLK15) to allow for quantitative real-time PCR. Data was normalized to a β-actin housekeeping gene. Relative quantification analysis was performed using the ΔCq method. KLK1-KLK15 expression was observed in both tissue types. However, KLK1, KLK8, KLK11, and KLK14 were found to be downregulated in ACC. We propose that this may represent a multi-parametric panel providing diagnostic and prognostic information.

Immune microenvironment and evasion mechanisms in adenoid cystic carcinomas of salivary glands

ObjectivesThe objective of the present study was to investigate the expression of immune checkpoints (PD-L1, PD-L2, PD-1 and CTLA-4), immune inhibitory molecule HLA-G, markers of tumor-infiltrating lymphocytes (TIL) and dendritic cells (DC), as well as its association with clinicopathological features of adenoid cystic carcinomas (ACC) of the salivary glands. Materials and methodsThirty-six samples from patients with ACC were analyzed immunohistochemically for the expression of PD-L1, PD-L2, PD-1, CTLA-4, HLA-G, CD8, GrB, CD1a and CD83. Positivity of HLA-G, PD-L1 and PD-L2 expression was defined by cut-offs values. CD8+ TIL was measured semiquantitatively and also using cut-off values obtained by the ROC curve considering recurrence of the lesion. ResultsACC showed low CD8+, GrB+ TIL, CD1a and CD83 populations, as well as scarce positivity for CTLA-4 and PD-1. In contrast, PD-L2 and HLA-G expression was increased, while no PD-L1 expression was detected. Interestingly, cases with lower CD8+ TIL density presented greater recurrence rates. ConclusionOur findings suggest that the ACC microenvironment exhibits low immunogenicity, represented by low TIL and DC density. Moreover, there seems to be activation of the immune inhibitory proteins/PD-L2 and HLA-G, a scenario that may favor tumor escape from the immune system and partially explain the poor prognosis of ACC.

A possible correlation of Ezrin and Fascin-1 in adenoid cystic carcinoma of salivary gland: an immunohistochemical study

Adenoid cystic carcinoma (ACC) of salivary gland is one of the most common epithelial salivary gland carcinomas and is characterized by extensive local tissue infiltration and poor long-term survival. All forms of ACC are characterized by prolonged but persistent growth, extensive perineural invasion and hematogenous metastases. Distant sites of metastasis are primarily lung, although bone and liver are also common. The incremental motility of malignant cells is a critical step in their migration, invasion and metastasis, which is regulated by reorganization of actin cytoskeleton and regulation of focal adhesion. Fascin-1 and ezrin are essential components of these cellular structures. The aim of this study is to evaluate the expression of these cytoskeleton-associated proteins in ACC as a prognostic indicator of invasiveness. Five cases of normal salivary gland tissue and 43 cases of adenoid cystic carcinoma (10 cases cribriform form, 15 cases tubular form and 18 cases solid form). Immunohistochmical staining for ezrin and fascin-1 antibodies were done for all specimens. Statistical analysis was performed using a commercially available software program (SPSS 19; SPSS, Chicago, IL, USA). The level of significance was set at P < 0.05. For both markers, statistically, the greatest mean area percent was recorded in solid pattern ACC, whereas the lowest values were recorded in normal tissue. These results indicating a synergistic effect between ezrin and fascin-1 during ACC invasion.

Cytologic diagnosis of adenoid cystic carcinoma of salivary glands and distinction from basal cell adenoma

Objective: To describe the cytologic features of adenoid cystic carcinoma (ADCC) of salivary glands, and to identify distinguishing cytologic features of ADCC and basal cell adenoma (BCA). Methods: A retrospective review of cytology smears of 30 cases of ADCC and 12 cases of BCA of salivary glands were performed. All cases were collected from Beijing Tongren Hospital, Capital Medical University from January 2010 to January 2017. Except for 2 aspirate smears of ADCC, all were touch imprint smears. All cases had further histological confirmation. Results: Neoplastic ductal cells of ADCC were arranged in three-dimensional clusters, sheets and singles. Hyaline globules were found in most cases (20/30, 66.7%). The nuclei were round to oval, showing varying degrees of nuclear atypia. These included (1) the nuclei were hyperchromatic, demonstrating coarse or slightly coarse, irregularly distributed chromatin; (2) the nuclei were slightly large and vary in size; (3) appearance of the nuclei had a different degree of irregularity (often mild). Nucleoli were common seen (21/30, 70.0%), and were prominent in some cases. Mitosis and necrosis were rare. Cytologically, BCA showed cell arrangements and nuclear features overlapped with those of ADCC. The cytologic difference between these two tumors included: (1) the tumor cells presented rarely in singles; (2) hyaline globules were very uncommon (1/12) in BCA; (3) nuclei of BCA were hypochromatic or slightly hyperchromatic, homogeneous and uniform in appearance and size, overall without nuclear atypia and they were smaller and slender then those of ADCC and (4) individual cells of BCA showed relatively abundant cytoplasm. Conclusions: The cytologic features of ADCC and BCA both overlap and different from each other. Most cases can be diagnosed by cytologic examination. The presence of hyaline globules is an important diagnostic clue of ADCC, although not pathognomonic. Nuclear atypia of neoplastic ductal cells is an essential cytological feature in the diagnosis of ADCC, and is the most reliable point for differential diagnosis of ADCC and BCA.

Adeno cystic carcinoma of salivary glands

Background: adenoid cystic carcinoma is the most frequent malignant tumor of submaxillary and minor salivary glands. Despite its slow growth, it shows an unfavorable prognosis because of its distant dissemination.Objective: to analyse our series of patients in relation to the literature.Materials and methods: 44 patients with mean age 52.47 years female gender. Of them, 61.3% were of minor salivary glands, 20.4% of submaxillary gland, and 18.2% the parotid gland. All patients underwent complete resection of the tumor followed by neck dissection in 34%. Co60 radiotherapy was administered to 43.2%. Mean follow up was 52.5 (range, 1-120) months.Results: 5-year recurrence rate was 36.8%. At 5 and 10 years, overall survival was 60 and 36%,respectively. Close surgical margins, requirement of adjuvant radiotherapy and stage significantly affected survival rate. The multivariate analysis showed that close margins was statistically significant for survival and associated with an unfavorable tendency for disease-free interval.Conclusions: extention of surgery to the neck and adyuvant radiotherapy was dependent of stage, clear surgical margins, neural invasion, positive nodes in the neck and hystological subtype.

Study of MYB-NFIB chimeric gene expression, tumor angiogenesis, and proliferation in adenoid cystic carcinoma of salivary gland.

Adenoid cystic carcinoma (ACC) is one of the common malignant tumors in salivary glands, and the clinical prognosis is poor with frequent distant metastasis which may lead to death. Expression of the MYB-NFIB chimeric gene in ACC has been reported recently. MYB is an oncogene with transcription regulating functions, and NFIB encodes nuclear transcription factor although detailed functions are unknown. This study investigated whether MYB-NFIB chimeric gene expression affects tumor angiogenesis and proliferation in salivary gland ACC. In 26 salivary gland ACC cases, MYB-NFIB chimeric gene expression was analyzed by RT-PCR and direct sequencing. Immunohistochemical studies for CD31, vascular endothelial growth factor (VEGF) and Ki-67 were performed. Tumor angiogenesis was evaluated by blood vessel (CD31-positive) density and tumor proliferation by Ki-67 labeling index, and the relationship with MYB-NFIB chimeric gene expression was analyzed. MYB-NFIB chimeric gene expression was detected in nine of 26 ACC cases. Blood vessel density was significantly higher in chimeric gene-expressing cases compared to non-expressing cases. VEGF score tended to be higher in chimeric gene-expressing cases than in non-expressing cases, while Ki-67 labeling index was not significantly different. The number of chimeric gene-expressing cases increased with age, peaking in the sixties age group and declining thereafter, while the number of non-expressing cases increased with age continuously. In ACC, blood vessel density was significantly higher in MYB-NFIB chimeric gene-expressing cases compared to non-expressing cases, which may be due to higher VEGF production capability. MYB-NFIB chimeric gene expression may also be related to the onset age of ACC.

Predictors of Outcome in Adenoid Cystic Carcinoma of Salivary Glands

Adenoid cystic carcinoma (ACC) is the second most common salivary gland malignancy and it has a high rate of recurrences and a poor long-term prognosis. Our aim was to assess the prognostic factors in ACC and study MYB-NFIB fusion and MYB protein expression in a large retrospective cohort of 135 patients with a median follow-up of 6.3 years. The 5- and 10-year local recurrence-free survival (RFS) rate of 94% and 78%, 5- and 10-year distant metastasis survival rate of 77% and 58%, and 5- and 10-year RFS of 66% and 44%. The following features were identified as adverse prognostic factors of RFS on univariate analysis: large tumor size, solid growth pattern, increased mitoses, positive margin, American Joint Committee on Cancer clinical staging, high-grade transformation, vascular invasion, nuclear atypia, open chromatin, prominent nucleoli, and tumor necrosis. However, on multivariate analysis, only increased mitoses (≥5/10 high-power fields), any solid growth pattern, and advanced American Joint Committee on Cancer TNM staging were independent adverse predictors for RFS. MYB immunoexpression and MYB-NFIB translocation were common findings in ACC, occurring in 72% and 59% of the tested ACCs, respectively. The sensitivity and specificity of MYB immunohistochemistry in detecting MYB-NFIB fusion was relatively low at 78% sensitivity and 50% specificity. The high prevalence of alterations leading to high expression of the MYB transcription factor family suggests that targeted approaches developed to suppress the expression of these oncogenic transcription factors and/or the transcriptional activity of these proteins would be a rational therapeutic approach to investigate in ACC.

Prognostic significance of p53 immunohistochemical expression in adenoid cystic carcinoma of the salivary glands: a meta-analysis.

Adenoid cystic carcinoma of salivary glands is a rare adenocarcinoma and has been placed in “high-risk” category as poor long-term prognosis. The purpose of this study was to investigate p53 protein expression in adenoid cystic carcinoma of salivary glands and its correlation with clinicopathological parameters and prognosis. Literatures were searched from PubMed, Embase, Cochrane Library and Web of Science, which investigated the relationships between p53 expression and pathological type, clinical stage, local recurrence, metastasis, nerve infiltration and overall survival. A total of 1,608 patients from 36 studies were included in the analysis. The results showed that p53-postive expression rate was 49% in adenoid cystic carcinoma of salivary glands (OR=10.34, 95%CI: 4.93-21.71, P < 0.0001). The p53-postive expression was closely related to tumor types (OR=0.30, 95%CI: 0.14-0.65, P < 0.0001). The tumor with solid histological subtype had a strong positive correlation with p53 expression. The combined analysis revealed that the p53-positive expression rate among patients in T1and T2 stage was 41.4%, compared to 53.2% among those in T3 and T4 stage. However, there was no significant correlation between tumor stage and p53 expression (OR=0.47, 95% CI: 0.17-1.29, P = 0.14). Besides, compared to patients with p53-negative expression, those with p53-positive expression had a greater chance of developing metastasis, local recurrence and nerve infiltration as well as poorer 5-year overall survival (P < 0.01). In conclusion, the p53 expression is related to the survival of adenoid cystic carcinoma of salivary glands. It can be considered as the auxiliary detection index in treatment and prognosis of adenoid cystic carcinoma of salivary glands.

Pleomorphic adenoma and adenoid cystic carcinoma of salivary glands: E-cadherin immunoexpression and analysis of the CDH1 -160C/A polymorphism

ObjectiveDespite their similar cellular origin, pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC) present distinct behaviors. This study aimed to analyze the immunoexpression of E-cadherin in PA and ACC of salivary glands, and to investigate differences in its expression in relation to E-cadherin gene (CDH1) -160C/A polymorphism. DesignTwenty-four PA (15 cell-rich and 9 cell-poor tumors) and 24 ACC (10 tubular, 8 cribriform and 6 solid tumors) were selected for the analysis of pattern of distribution, and cellular localization of E-cadherin. In addition, E-cadherin expression was evaluated using the H-score scoring system. The CDH1 -160C/A polymorphism was investigated by PCR-RFLP. ResultsNo significant differences in pattern of distribution (p=0.181) and cellular localization (p=0.192) of E-cadherin were observed between PA and ACC. Comparison of PA and ACC cases revealed a higher median H-score in the latter (p=0.036). Cell-rich PA presented a higher H-score than cell-poor tumors (p=0.013), whereas no significant differences in E-cadherin expression were observed between ACC subtypes (p=0.254). The heterozygous genotype of the CDH1 -160C/A polymorphism was detected in only one PA and one ACC. H-scores for tumors carrying the polymorphism were below the lower quartile of their respective groups. ConclusionsThe results suggest that E-cadherin expression in PA and ACC is mainly related to cellular composition (epithelial cells versus myoepithelial cells) and degree of differentiation of myoepithelial cells in these tumors. The CDH1 -160C/A polymorphism does not seem to significantly influence the expression of E-cadherin in PA and ACC of salivary glands.