Clinicopathological characteristics and perineural invasion in adenoid cystic carcinoma: a systematic review

Dantas, Afonso Nóbrega; Morais, Everton Freitas de; Macedo, Robson; Tinôco, João Maria de Lima; Morais, Maria de Lourdes Silva de Arruda

doi:10.1016/j.bjorl.2014.07.016

Cited by 68 publications

(62 citation statements)

References 24 publications

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“…Overall, ACC has been reported to have a 5-year survival rate of 55% – 89% (3, 7–12), 15 or 20-year survival of 23 – 40% (5, 11, 12), local recurrence rate of 16– 67%, and DM rate of 8 – 46% (1, 9, 11, 13–15). The 5-year and 20-year recurrence free survival in our cohort was 66% and 36% respectively, emphasizing the tendency of ACC to develop late recurrence.…”

Section: Discussionmentioning

confidence: 99%

“…The 5-year and 20-year recurrence free survival in our cohort was 66% and 36% respectively, emphasizing the tendency of ACC to develop late recurrence. The most frequent sites of ACC were reported to be in minor salivary glands of the larynx, pharynx, and oral cavity, in particular the palate (7, 13, 18, 26, 31). However, ACC of the major salivary glands do occur at a frequency of 29% to 43% (18, 26).…”

Section: Discussionmentioning

confidence: 99%

“…Clinically, ACC is known for its high risk of recurrence, especially late recurrence. The rate of local recurrence and distant metastasis (DM) is 16–67% and 8–46% respectively (1, 9, 11, 13–15). The reported independent prognostic factors include tumor site, tumor stage, nodal status, margin status, solid pattern, lymphovascular invasion, and intraneural invasion (3, 5, 14–19).…”

Section: Introductionmentioning

confidence: 99%

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Predictors of Outcome in Adenoid Cystic Carcinoma of Salivary Glands

Xu¹,

Drill

et al. 2017

American Journal of Surgical Pathology

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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-year and 10-year local recurrence-free survival rate of 94% and 78%, 5-year and 10-year distant metastasis survival rate of 77% and 58%, and 5-year and 10-year recurrence free survival (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, AJCC 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 AJCC TNM staging were independent adverse predictors for RFS. MYB immuno-expression 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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Predictors of Outcome in Adenoid Cystic Carcinoma of Salivary Glands

Xu¹,

Drill

et al. 2017

American Journal of Surgical Pathology

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“…PNI is a striking characteristic of SACC that is responsible for incomplete surgical resection, locoregional recurrence and distant metastasis (17). PNI also has been regarded as an independent indicator of aggressive behavior and poor prognosis in several neurotrophic cancers, most notably prostate and pancreatic cancer (18,19).…”

Section: Discussionmentioning

confidence: 99%

Schwann cells promote EMT and the Schwann-like differentiation of salivary adenoid cystic carcinoma cells via the BDNF/TrkB axis

et al. 2015

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Abstract. Perineural invasion (PNI) is a striking biological behavior observed in salivary adenoid cystic carcinoma (SACC). The present study was designed to establish a co-culture model of SACC cells with Schwann cells (SCs), and then study epithelial-mesenchymal transition (EMT) and the Schwann-like differentiation of SACC cells to investigate the likely molecular mechanism of PNI. The co-culture models of SCs with tumor cells (SACC-83, SACC-LM and MEC-1) were established using a Transwell system. An elevated concentration of brain-derived neurotrophic factor (BDNF) was detected by ELISA assay in the co-cultured medium of the SACC-83 group and SACC-LM group rather than the MEC-1 group. The EMT process and Schwann-like differentiation in SACC-83 cells were analyzed by RT-PCR, western blotting, immunofluorescence, photography, and migration and perineural invasion assays. The SACC-83 cells under the co-culture condition with SCs changed to a mesenchymal morphology and had higher migration and invasion capabilities compared with the solely cultured SACC-83 cells, accompanied by the downregulation of E-cadherin and upregulation of N-cadherin and vimentin. The co-cultured SACC-83 cells also developed Schwann-like differentiation with increased expression of SC markers, S100A4 and GFAP. However, inhibition of tropomyosin-related kinase B (TrkB) by K252a markedly blocked these effects. Additionally, the expression and correlation of TrkB, E-cadherin and S100A4 were analyzed by immunohistochemistry in 187 primary SACC cases. The levels of TrkB and S100A4 expression were both positively associated with PNI in the SACC cases, while E-cadherin expression was negatively associated with PNI. Elevated expression of TrkB was significantly correlated with the downregulated expression of E-cadherin and the upregulated expression of S100A4 in the SACC cases. Our results suggest that SCs play a pivotal role in the PNI process by inducing the EMT process and the Schwann-like differentiation of SACC cells via the BDNF/TrkB axis. Interruption of the interreaction between SACC cells and SCs by targeting the BDNF/TrkB axis may be a potential strategy for anti-PNI therapy in SACC.

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“…Adenoid cystic carcinoma (ACC) of the salivary glands also has a particular propensity for nerve invasion, with up to 62% displaying perineural invasion. (38) …”

Section: Epidemiology Of Perineural Growthmentioning

confidence: 99%

Molecular mechanisms of perineural spread of cutaneous carcinoma: a potential role for receptor tyrosine kinases and other biomarkers

Schmidt¹

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Perineural invasion and spread of cutaneous squamous cell carcinoma of the head and neck (cSCCHN) is associated with worse prognosis and high rates of locoregional recurrence. It occurs in less than 5% of cases, but given the high incidence of cSCC in Australia, portends significant morbidity and mortality. Primary tumour biology remains poorly understood and precise molecular mechanisms by which malignant squamous cells invade and progress axially within the perineural space remain unclear. Thus, there is no targeted therapy for perineural spread of cSCCHN or other neurotropic malignancies. Dysregulation of cell membrane receptor trafficking is a hallmark of cancer and such receptors are potential therapeutic targets.Over-expression of the epidermal growth factor receptor (EGFR) is well described in squamous cell carcinoma and the monoclonal antibody cetuximab is approved for advanced mucosal head Ultimately, we aim to improve survival and quality of life for sufferers of this morbid form of tumour spread. Our findings may also have implications for other neurotropic malignancy, including pancreatic, gastric, colorectal and prostate cancers. 4 Declaration by authorThis thesis is composed of my original work, and contains no material previously published or written by another person except where due reference has been made in the text. I have clearly stated the contribution by others to jointly-authored works that I have included in my thesis.

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Clinicopathological characteristics and perineural invasion in adenoid cystic carcinoma: a systematic review

Cited by 68 publications

References 24 publications

Predictors of Outcome in Adenoid Cystic Carcinoma of Salivary Glands

Predictors of Outcome in Adenoid Cystic Carcinoma of Salivary Glands

Schwann cells promote EMT and the Schwann-like differentiation of salivary adenoid cystic carcinoma cells via the BDNF/TrkB axis

Molecular mechanisms of perineural spread of cutaneous carcinoma: a potential role for receptor tyrosine kinases and other biomarkers

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