Project description:Invasive malignant pleomorphic adenoma (IMPA) results from the malignant transformation of pleomorphic adenoma (PA). The former is a high-grade malignant tumor, whereas the latter is a benign opposite. Study on the molecular mechanism in the progression of PA to IMPA will be of benefit to elucidate the reasons for different biological behaviors among these salivary gland tumors with the same origin. But there is no valuable and non-invasive biomarker to screen IMPA currently. Studies showed many salivary molecules can detect several systemic diseases. We aimed to investigate whether salivary mRNAs (mRNA) can act as a biomarker to detect IMPA.
Project description:N6-methyladenosine (m6A) is one of the most popular RNA modifications, which is widely found in messenger RNAs (mRNAs) .In our study,we provide m6A profiles of human invasive malignant pleomorphic adenoma, which open an avenue for in-depth knowledge and understanding of m6A topology in invasive malignant pleomorphic adenoma.
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.
Project description:BACKGROUND: potential epigenetic biomarkers for malignant transformation to carcinoma ex pleomorphic adenoma (Ca ex PSA) have been sought previously with and without specific comparison with the benign variant, pleomorphic salivary adenoma (PSA). Previous analysis has been limited by a non-quantitative approach. We sought to demonstrate quantitative promoter methylation across a panel of tumour suppressor genes (TSGs) in both Ca ex PSA and PSA. METHODS: quantitative methylation-specific real-time polymerase chain reaction (qMSP) analysis of p16(INK4A), CYGB, RASSF1, RAR?, human telomerase reverse transcriptase (hTERT), Wilms' tumour 1 (WT1) and TMEFF2 gene promoters was undertaken on bisulphite-converted DNA, previously extracted from archival fixed tissue specimens of 31 Ca ex PSA and an unrelated cohort of 28 PSA. All target regions examined had formerly been shown to be hypermethylated in salivary and/or mucosal head and neck malignancies. RESULTS: the qMSP demonstrated abnormal methylation of at least one target in 20 out of 31 (64.5%) Ca ex PSA and 2 out of 28 (7.1%) PSA samples (P<0.001). RASSF1 was the single gene promoter for which methylation is shown to be a statistically significant predictor of malignant disease (P<0.001) with a sensitivity of 51.6% and a specificity of 92.9%. RAR?, TMEFF2 and CYGB displayed no apparent methylation, while a combinatory epigenotype based on p16, hTERT, RASSF1 and WT1 was associated with a significantly higher chance of detecting malignancy in any positive sample (odds ratio: 24, 95% CI: 4.7-125, P<0.001). CONCLUSIONS: we demonstrate the successful application of qMSP to a large series of historical Ca ex PSA samples and report on a panel of TSGs with significant differences in their methylation profiles between benign and malignant variants of pleomorphic salivary adenoma. qMSP analysis could be developed as a useful clinical tool to differentiate between Ca ex PSA and its benign precursor.
Project description:The most common benign salivary gland tumor is the pleomorphic adenoma (PA). They can attain grotesque proportions and weigh several kilograms. They can cause facial disfigurement and, if untreated, could lead to airway compromise. We report a case of a large PA arising from the left submandibular salivary gland in a 20-year-old black female. The lesion measured ∼16 × 15 × 12 cm.
Project description:Salivary and mammary gland tumors show morphological similarities and share various characteristics, including frequent overexpression of hormone receptors and female preponderance. Although this may suggest a common etiology, it remains unclear whether patients with a salivary gland tumor carry an increased risk of breast cancer (BC). Our purpose was to determine the risk of BC in women diagnosed with salivary gland carcinoma (SGC) or pleomorphic adenoma (SGPA). BC incidence (invasive and in situ) was assessed in two nationwide cohorts: one comprising 1567 women diagnosed with SGC and one with 2083 women with SGPA. BC incidence was compared with general population rates using standardized incidence ratio (SIR). BC risk was assessed according to age at SGC/SGPA diagnosis, follow-up time and (for SGC patients) histological subtype. The mean follow-up was 7.0 years after SGC and 9.9 after SGPA diagnosis. During follow-up, 52 patients with SGC and 74 patients with SGPA developed BC. The median time to BC was 6 years after SGC and 7 after SGPA. The cumulative risk at 10 years of follow-up was 3.1% after SGC and 3.5% after SGPA (95% Confidence Interval (95%CI) 2.1%-4.7% and 2.6%-4.6%, respectively). BC incidence was 1.59 times (95%CI 1.19-2.09) higher in the SGC-cohort than expected based on incidence rates in the general population. SGPA-patients showed a 1.48 times (95%CI 1.16-1.86) higher incidence. Women with SGC or SGPA have a slightly increased risk of BC. The magnitude of risk justifies raising awareness, but is no reason for BC screening.