Phospholipase C-γ1 expression correlated with cancer progression of potentially malignant oral lesions.

BACKGROUND: Phospholipase C-γ1 (PLCγ1) is required for cellular migration during tumor progression and invasion of oral squamous cell carcinoma (OSCC) cells. The objective of the current study was to determine immunoexpression pattern of PLCγ1 in oral potentially malignant lesions (OPLs) and evaluate PLCγ1 usefulness as a biomarker for predicting clinical behavior in the carcinogenesis of OPL. METHODS: In a retrospective follow-up study, the expression pattern of PLCγ1 protein was determined using immunohistochemistry in samples from 68 patients, including untransformed cases (n = 38) and malignant-transformed cases (n = 30). The corresponding post-malignant lesions (OSCCs) were also performed. RESULTS: We observed that elevated expression of PLCγ1 in 40 of 68 (59%) general OPLs and 23 of 30 (77%) OSCCs compared with that in normal oral mucosa. Kaplan-Meier analysis revealed that patients with PLCγ1 positivity had a significantly higher incidence of OSCC than those with PLCγ1 negativity. Cox regression analysis revealed that PLCγ1 expression patterns were significantly associated with increased risk of malignant progression. In addition, the correlation between PLCγ1 expression in pre-malignant OPL and that in post-malignant OSCC was significant (P = 0.004). CONCLUSION: These data indicate that PLCγ1 expression in OPL correlated with oral cancer progression, and PLCγ1 may serve as a useful marker for the identification of high-risk OPL into OSCC.

Phosphorylated p120-catenin expression has predictive value for oral cancer progression.

AIMS: Recent studies have shown that phosphorylation of p120-catenin (p120) promotes progression and invasion of oral squamous cell carcinoma (OSCC) cells. The objective of the current study was to evaluate the usefulness of phosphorylated p120-catenin (pp120) as a biomarker for predicting clinical behaviour in the carcinogenesis of potentially malignant oral lesions. METHODS: In a retrospective follow-up study, the expression pattern of pp120 protein was determined using immunohistochemistry in samples from 68 patients with potentially malignant oral lesions, including patients with untransformed lesions (n=38) and patients with malignant transformed lesions (n=30). Analysis of corresponding post-malignant lesions (OSCCs) was also performed. RESULTS: There was high expression of pp120 in 35 of 68 (51.5%) of general potentially malignant oral lesions and 23 of 30 (76.7%) of OSCCs compared with expression in normal oral mucosa. Kaplan-Meier analysis revealed that patients with potentially malignant oral lesions expressing high levels of membranous pp120 had a significantly higher incidence of OSCC than those expressing low expressing pp120 (p=0.002; log-rank test). Cox regression analysis revealed that this pp120 expression pattern was significantly associated with a 3.43-fold increase in the risk of malignant progression (p=0.007). In addition, there was a significant correlation between high levels of membranous expression of pp120 in pre-malignant lesions and cytoplasmic expression in post-malignant lesions (p=0.028). CONCLUSIONS: The data indicated that a high level of membranous expression of pp120 in potentially malignant oral lesions is an early event during oral carcinogenesis, and that the mislocalisation of expression of pp120 from the cell membrane to the cytoplasm is associated with oral cancer progression. pp120 may serve as a useful marker for the identification of a high risk of potentially malignant oral lesions progressing to OSCC.

Generic and oral quality of life is affected by oral mucosal diseases.

BACKGROUND: The generic and oral health-related quality of life (QoL) has provided opportunity for investigation of the interrelations among generic health, oral health, and related outcomes. The purpose of this study was to identify the generic and oral QoL in the patients with oral mucosal disease (OMD). METHODS: Five hundred and thirty-eight OMDs were recruited in this study. The instruments applied were Chinese version of the 36-item short form health survey (SF-36) and the short-form of Oral Health Impact Profile (OHIP-14). RESULTS: The mean score of sum OHIP-14 was significantly higher in the patients with OMD (10.81 ± 9.01) compared with those in the healthy subjects (HS) (6.55 ± 6.73) (p < 0.001, Mann-Whitney U test). 56.51% of the OMD patients and 12.94% of the HS reported at least one oral negative impact (p < 0.001, Chi-square test). The overall mean score of SF-36 was significantly lower in the patients with OMD (74.54 ± 12.77) compared with those in the HS (77.97 ± 12.39) (p = 0.021, t-test). CONCLUSIONS: Administration of specific and generic questionnaires of QoL can provide us a detailed picture of the impact of OMDs on patients, and both generic and oral QoL were impaired in the patients with OMD.

DAPK promoter hypermethylation in tissues and body fluids of oral precancer patients.

Death-associated protein kinase (DAPK) has been suggested as a tumor suppressor gene. A high frequency of DAPK promoter hypermethylation has been noted in head and neck cancers and other solid tumors, and it has been used as a tumor marker in molecular detection strategies. Our aim was to examine DAPK promoter hypermethylation in tissue, blood, and salivary rinse samples of oral precancer patients (OPs) and to explore the potential role in oral carcinogenesis. DAPK hypermethylation was analyzed in 77 OPs and 32 oral squamous cell carcinomas (OSCCs) by real-time quantitative methylation-specific PCR (QMSP). We compared the hypermethylation expression between two groups and analyzed the associations with clinicopathologic parameters. The promoter hypermethylation frequency of DAPK in tissue (46.9%) and blood (52.2%) of OSCCs was significantly higher than those in OPs (19.5%, P = 0.004; 22.4%, P = 0.007, respectively). DAPK promoter hypermethylation expression in blood was correlated with its expression in tissue (r = 0.49, P < 0.000). The OP patients who smoked more than 20 years were found 40.0% tissue DAPK hypermethylation in contrast with 10.7% tissue DAPK hypermethylation in the patients whose smoking duration ≦20 years (P = 0.010). Our results suggest that DAPK hypermethylation is an early event in oral carcinogenesis and blood DAPK hypermethylation might be a potential minimal invasive biomarker for OSCC early detection.

Podoplanin and ABCG2: malignant transformation risk markers for oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a potentially malignant disorder associated with an increased risk for oral cancer. The purpose of this study was to determine protein expression of podoplanin and ATP-binding cassette, G2 subfamily (ABCG2) in patients with OLP and evaluate their use as biomarkers for OLP malignant transformation risk. METHODS: Podoplanin and ABCG2 expressions were determined in samples from 110 patients with untransformed OLP and 9 patients with malignant transformed OLP (mean follow-up of 5.1 years). We compared podoplanin expression, ABCG2 expression, and clinicopathologic parameters between the two groups. RESULTS: Podoplanin expression was observed in 48 of 110 (43.6%) cases of untransformed OLP and in 8 of 9 (88.9%) cases of transformed OLP. ABCG2 expression was found in 23 of 110 (20.9%) cases of untransformed OLP and in 6 of 9 (66.7%) cases of transformed OLP. Multivariate regression analysis revealed that podoplanin or ABCG2 expression was associated with 17.13-fold [95% confidence interval (95% CI), 1.71-171.22; P = 0.016] or 6.04-fold (95% CI, 1.20-30.36; P = 0.029) increased risk of malignant transformation, respectively. The risk of OLP malignant transformation was considerably higher with coexpression of podoplanin and ABCG2 than without coexpression of podoplanin and ABCG2 (odds ratio, 25.24; 95% CI, 4.48-142.27; P < 0.001). CONCLUSIONS: The expressions of podoplanin and ABCG2 in OLP were significantly associated with malignant transformation risk. IMPACT: Our data suggested that podoplanin and ABCG2 may be used as biomarkers for risk assessment of oral malignant transformation in patients with OLP.

[Aldosterone-to-renin ratio threshold for screening primary aldosteronism in Chinese hypertensive patients].

OBJECTIVE: In recent years, the assessment of the plasma aldosterone-to-renin ratio (ARR) has become a most effectively and commonly used method for screening primary aldosteronism from hypertensive patients. It is known that there is a large variance in ARR value between races and ARR is affected by many factors, such as drugs, posture and serum potassium etc. The objective of this study is to establish the threshold of ARR for screening primary aldosteronism in Chinese hypertensive patients. METHODS: A total of 110 hypertensive patients were recruited and divided into essential hypertension group (n=65) and adenoma/hyperplasia group (n=45) according to the adrenal contrast CT scan. Antihypertensive drugs which can affect ARR such as beta-blockers, dihydropyridine calcium channel blockers (CCBs), ACE inhibitors (ACEIs), angiotensin II receptor blockers (ARBs) and clonidine, were withdrawn for at least 2 weeks. Washout period for diuretics including spironolactone were 4 weeks. Non-dihydropyridine calcium channel blockers (slow released verapamil) and/or alpha-blocker (terazosin) are allowed for controlling blood pressure when needed. If the serum potassium value<3.6 mmol/L, an oral potassium supplement was prescribed. After keeping upright position for 2 hours, blood samples were drawn for PRA and PAC measurement between 9:00AM-10:00AM. RESULTS: ARR was 100.00+/-48.65 (14.19-285.16) pg/ml vs ngxml-1xh-1 in patients with essential hypertension and 699.33+/-213.33 (185.8-2150) pg/ml vs ngxml-1xh-1 in patients with adenoma/hyperplasia. ARR value was greater than 240 in 42 out of 45 patients (93.3%) with adenoma/hyperplasia and was less than 240 in 59 out of 65 (90.7%) patients with essential hypertension. We used ARR 240 as the cut-off threshold for screening primary aldosteronism in another 178 hypertensive patients and ARR was greater than 240 in all 15 patients with confirmed primary aldosteronism. CONCLUSION: It is suitable to use upright ARR 240 as a cut-off threshold for screening primary aldosteronism in Chinese hypertensive patients.