Factors affecting the accuracy of anti-BRAF V600E immunohistochemistry results in ameloblastomas.

BACKGROUND: There are still some controversies about the results of anti-BRAF V600E-specific antibody immunohistochemistry in ameloblastomas. This study aimed to examine the accuracy of V600E-specific antibody immunohistochemistry in detection of BRAF V600E mutation in ameloblastoma tissue sections of different ages. METHODS: The BRAF V600E status of 64 ameloblastoma specimens was assessed using both Sanger sequencing and V600E-specific antibody immunohistochemistry, and the sensitivity, specificity, positive predictive value, and negative predictive value were calculated. The difference in V600E-specific antibody immunohistochemistry staining intensity among the three groups of ameloblastoma tissue blocks of different ages was evaluated by chi-square test. The consistency between V600E-specific antibody immunohistochemistry and DNA sequencing results and the V600E-specific antibody immunohistochemistry staining intensity of 15 paired newly-cut and 3-month storage sections of the same 15 ameloblastomas were also compared. RESULTS: For detection of BRAF V600E mutation, the V600E-specific antibody immunohistochemistry had high sensitivity (98.21% 55/56), specificity (87.5% 7/8), positive predictive value (98.21% 55/56), and negative predictive value (87.5% 7/8). Heterogeneity of the staining intensity was observed in the same tissue section, but all or none expression pattern was noticed in the solid tumor nests. The storage time of paraffin tissue blocks ranging from 2 to 14 years did not affect the V600E-specific antibody-positive staining intensity. However, the three-month storage sections showed a significant diminishment of V600E-specific antibody-positive staining signals. CONCLUSIONS: The BRAF V600E-specific antibody immunohistochemistry is suitable for routine detection of BRAF V600E mutation in ameloblastomas. The all or none expression pattern suggests the BRAF V600E mutation may be an early event in the pathogenesis of ameloblastoma.

ZNF582 hypermethylation as a prognostic biomarker for malignant transformation of oral lesions.

OBJECTIVES: This hospital-based cohort study evaluated whether ZNF582 and PAX1 methylation levels at baseline can be used as biomarkers to identify lesions with a high potential for malignant transformation in patients with normal mucosa and oral potentially malignant disorders. PATIENTS AND METHODS: We recruited 171 adult patients with normal mucosa and oral potentially malignant disorders in 2012-2014. They were followed until 2017. Outcomes, including advanced histopathological findings and oral cancer occurrence, were obtained from medical charts, the Taiwan Cancer Registry, and cause-of-death data. Kaplan-Meier analysis and Cox proportional hazards regression models were used to examine the association of ZNF582 and PAX1 methylation levels at baseline with subsequent outcome occurrences. RESULTS: After 260,192 days of follow-up, 11 cases of oral cancer and 4 cases of advanced histopathological progression occurred. Patients with higher ZNF582 and PAX1 methylation levels at baseline had a higher incidence of disease progression. After adjustment for all studied factors using Cox proportional hazards regression models, ZNF582m level (adjusted hazard ratio, 11.41; 95% CI, 2.05-63.36; p = 0.005) was the only significant and independent predictor of disease progression. CONCLUSIONS: ZNF582 hypermethylation can be an effective and noninvasive biomarker for identifying oral lesions with a high potential for malignant transformation.

ß-glucan therapy converts the inhibition of myeloid-derived suppressor cells in oral cancer patients.

OBJECTIVES: The myeloid-derived suppressor cells (MDSCs) frequently have a high expansion in cancer patients. This research explored whether administration of ß-glucan could increase anti-tumor immunity in oral squamous cell carcinoma (OSCC) patients. MATERIALS AND METHODS: This study evaluated the MDSC level of circulating blood as CD33+ /CD11b+ /HLA-DR-/low by flow cytometry in 30 healthy donors (HDs, group I), in 48 oral squamous cell carcinoma (OSCC) patients before and after 14-day preoperative administration of ß-glucan (group II), and in 52 OSCC patients without taking ß-glucan (group III). RESULTS: A significantly higher mean MDSC level was observed in 100 OSCC patients than in 30 HDs (p < .001). There was a significant reduction of the mean MDSC level in group II patients after taking ß-glucan (p < .001). Moreover, we discovered a significantly higher recurrence-free survival (RFS) in group II than in group III patients (p = .026). Finally, the multivariate Cox regression further identified the MDSC level ≤1% and administration of ß-glucan as more favorable prognostic factors for OSCC patients. CONCLUSION: Preoperative administration of ß-glucan can augment anti-tumor immunity and increase RFS rate via subversion of suppressive function of MDSC in OSCC patients.

Clinical outcomes of adjunctive indocyanine green-diode lasers therapy for treating refractory periodontitis: A randomized controlled trial with in vitro assessment.

BACKGROUND/PURPOSE: It is still challengeable to treat periodontal pockets refractory to mechanical debridement. This study is to evaluate the potential of indocyanine green (ICG)-diode laser-based photothermal therapy (PTT) for solving this dilemma. METHODS: Bone marrow-derived mesenchymal stem cells (BMSCs) and periodontal ligament cells (PDLCs) were incubated with phosphate-buffered saline, chlorhexidine, or ICG, non-irradiated or irradiated with 810-nm diode lasers, and the cell viability was evaluated. Patients with teeth refractory to mechanical periodontal debridement on different quadrants were recruited. At baseline (T0), all examined teeth received scaling and root planing, and those on the test quadrant (PTT group) received ICG-diode laser treatment. The outcome was evaluated using clinical parameters and cytokines in the gingival crevicular fluids at 4-6 weeks (T1) and 6 months (T2). RESULTS: In ICG-treated cultures, the viability of BMSCs and PDLCs was recovered on day 4, and laser irradiation inhibited the metabolic activities of BMSCs. 22 patients with 30 control teeth and 35 PTT-treated teeth were examined. All examined teeth showed modest reductions in probing pocket depth (PPD), clinical attachment loss (CAL), bleeding upon probing (BOP), and plaque score at T1 and T2 and significant reductions in IL-1ß and MMP-8 at T2. Compared with controls, BOP was reduced more prominently, IL-1ß and MMP-8 were significantly lower, and reductions in PPD and CAL were slightly greater in the PTT group at T1 (0.05-0.19 mm). CONCLUSION: ICG-diode laser-based PTT is compatible to periodontium and assists in faster resolution of gingival inflammation in periodontal pockets refractory to mechanical debridement.

Gastric parietal cell and thyroid autoantibodies in patients with burning mouth syndrome.

BACKGROUND/PURPOSE: Gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) are organ-specific autoantibodies. This study mainly assessed the frequencies of serum GPCA, TGA, and TMA positivities in burning mouth syndrome (BMS) patients. METHODS: Serum GPCA, TGA, and TMA levels were measured in 884 BMS patients and in 442 age- and sex-matched healthy control subjects. RESULTS: We found that 12.3%, 21.6%, and 22.7% of 884 BMS patients and 1.8%, 2.3%, and 2.9% of 442 healthy control subjects had the serum GPCA, TGA, and TMA positivities, respectively. BMS patients had significantly higher frequencies of GPCA, TGA, and TMA positivities than healthy control subjects (all P-values < 0.001). We also found that 20 (2.3%), 130 (14.7%), and 181 (20.5%) BMS patients and 3 (0.7%), 8 (1.8%), and 6 (1.4%) healthy control subjects had the presence of three (GPCA + TGA + TMA), two (GPCA + TGA, GPCA + TMA, or TGA + TMA), or one (GPCA only, TGA only, or TMA only) organ-specific autoantibody in their sera, respectively. Of 255 TGA/TMA-positive BMS patients whose serum thyroid-stimulating hormone (TSH) levels were measured, 87.8%, 5.1%, and 7.1% of these TGA/TMA-positive BMS patients had normal, lower, and higher serum TSH levels, respectively. CONCLUSION: Approximately 37.5% of 884 BMS patients have serum GPCA/TGA/TMA positivity. Moreover, 12.3%, 21.6%, and 22.7% of 884 BMS patients have the serum GPCA, TGA, and TMA positivities, respectively. Only 5.1% and 7.1% of TGA/TMA-positive BMS patients have hyperthyroidism and hypothyroidism, respectively. It needs further studies to know whether GPCA-positive BMS patients may finally become as having autoimmune atrophic gastritis.

Does serum gastric parietal cell antibody titer have influence on anemia and vitamin B12 deficiency in atrophic glossitis patients?

BACKGROUND/PURPOSE: Our previous study found 284 gastric parietal cell antibody (GPCA)-positive atrophic glossitis (AG) patients (so-called GPCA+AG patients in this study) in a group of 1064 AG patients. This study evaluated whether high-titer (GPCA titer ≥ 160) GPCA+AG patients had greater frequencies of anemia, vitamin B12 deficiency, macrocytosis, and hyperhomocysteinemia than low-titer (GPCA titer < 160) GPCA+AG patients. METHODS: Complete blood count, serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 117 high-titer GPCA+AG patients, 167 low-titer GPCA+AG patients, and 532 healthy control subjects were measured and compared. RESULTS: We found that 12.0%, 29.1%, 23.1%, 16.2%, 1.7%, and 23.1% of 117 high-titer GPCA+AG patients and 5.4%, 17.4%, 17.4%, 7.2%, 1.2%, and 14.4% of 167 low-titer GPCA+AG patients were diagnosed as having macrocytosis, blood hemoglobin, iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia, respectively. Moreover, both 117 high-titer and 167 low-titer GPCA+AG patients had significantly greater frequencies of macrocytosis, blood hemoglobin, serum iron and vitamin B12 deficiencies, and hyperhomocysteinemia than 532 healthy control subjects (all P-values < 0.05). In addition, 117 high-titer GPCA+AG patients also had greater frequencies of anemia (P = 0.029, statistically significant), serum vitamin B12 deficiency (P = 0.027, statistically significant), macrocytosis (P = 0.075, marginal significance), and hyperhomocysteinemia (P = 0.085, marginal significance) than 167 low-titer GPCA+AG patients. CONCLUSION: For GPCA+AG patients, high-titer GPCA+AG patients have greater frequencies of anemia, serum vitamin B12 deficiency, macrocytosis, and hyperhomocysteinemia than low-titer GPCA+AG patients.

Hematinic deficiencies, hyperhomocysteinemia, and gastric parietal cell antibody positivity in atrophic glossitis patients with normocytosis.

BACKGROUND/PURPOSE: Normocytosis is defined as having the mean corpuscular volume (MCV) between 80 fL and 99.9 fL. This study evaluated whether 944 atrophic glossitis (AG) patients with normocytosis had significantly higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity than 532 healthy control subjects or 1064 AG patients. METHODS: Complete blood count, serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 944 AG patients with normocytosis, 1064 AG patients, and 532 healthy control subjects were measured and compared. RESULTS: We found that 12.4%, 14.5%, 2.3%, 2.0%, 9.0%, and 25.7% of 944 AG patients with normocytosis had blood hemoglobin (Hb), iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity, respectively. Furthermore, 944 AG patients with normocytosis had significantly higher frequencies of blood Hb, iron, vitamin B12, folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than 532 healthy control subjects (all P-values < 0.01). On the contrary, 944 AG patients with normocytosis had significantly lower frequencies of blood Hb and vitamin B12 deficiencies and hyperhomocysteinemia than overall 1064 AG patients (all P-values < 0.05). CONCLUSION: We conclude that there are significantly higher frequencies of anemia and serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity in AG patients with normocytosis than in healthy control subjects. On the contrary, AG patients with normocytosis have significantly lower frequencies of blood Hb and vitamin B12 deficiencies and hyperhomocysteinemia than overall AG patients.

Atrophic glossitis: Etiology, serum autoantibodies, anemia, hematinic deficiencies, hyperhomocysteinemia, and management.

Atrophic glossitis (AG) is characterized by the partial or complete absence of filiform papillae on the dorsal surface of the tongue. AG may reflect the significant deficiencies of some major nutrients including riboflavin, niacin, pyridoxine, vitamin B12, folic acid, iron, zinc, and vitamin E. Moreover, protein-calorie malnutrition, candidiasis, Helicobacter pylori colonization, xerostomia, and diabetes mellitus are also the etiologies of AG. Our previous study found the serum gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) positivities in 26.7%, 28.4%, and 29.8% of 1064 AG patients, respectively. We also found anemia, serum iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia in 19.0%, 16.9%, 5.3%, 2.3%, and 11.9% of 1064 AG patients, respectively. Moreover, GPCA-positive AG patients tended to have relatively higher frequencies of hemoglobin, iron, and vitamin B12 deficiencies and hyperhomocysteinemia than GPCA-negative AG patients. Supplementations with vitamin BC capsules plus corresponding deficient hematinics for those AG patients with hematinic deficiencies can achieve complete remission of oral symptoms and AG in some AG patients. Therefore, it is very important to examine the complete blood count, serum hematinic, homocysteine, and autoantibody levels in AG patients before we start to offer treatments for AG patients.

Anemia, hematinic deficiencies, and gastric parietal cell antibody positivity in atrophic glossitis patients with or without hyperhomocysteinemia.

BACKGROUND/PURPOSE: Our previous study found that 127 of 1064 atrophic glossitis (AG) patients have hyperhomocysteinemia. This study assessed whether the AG patients with hyperhomocysteinemia had significantly higher frequencies of anemia, hematinic deficiencies, and serum gastric parietal cell antibody (GPCA) positivity than AG patients without hyperhomocysteinemia or healthy control subjects. METHODS: The blood hemoglobin (Hb) and serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 127 AG patients with hyperhomocysteinemia, 937 AG patients without hyperhomocysteinemia, and 532 healthy control subjects were measured and compared. RESULTS: We found that 127 AG patients with hyperhomocysteinemia had significantly higher frequencies of blood Hb and serum iron, vitamin B12, and folic acid deficiencies and serum GPCA positivity than 532 healthy control subjects (all P-values < 0.001) and significantly higher frequencies of blood Hb and serum vitamin B12 and folic acid deficiencies and serum GPCA positivity than 937 AG patients without hyperhomocysteinemia (all P-values < 0.001). Moreover, 127 AG patients with hyperhomocysteinemia had significantly higher frequencies of macrocytic anemia and significantly lower frequencies of normocytic anemia than 937 AG patients without hyperhomocysteinemia (both P-values < 0.001). Pernicious anemia (22 cases) was found only in AG patients with hyperhomocysteinemia but not in AG patients without hyperhomocysteinemia. CONCLUSION: AG patients with hyperhomocysteinemia had significantly higher frequencies of anemia, serum iron, vitamin B12, and folic acid deficiencies, and serum GPCA positivity than healthy control subjects and significantly higher frequencies of anemia, serum vitamin B12 and folic acid deficiencies, and serum GPCA positivity than AG patients without hyperhomocysteinemia.

Anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody positivity in 884 patients with burning mouth syndrome.

BACKGROUND/PURPOSE: Burning mouth syndrome (BMS) is characterized by burning sensation of the oral mucosa in the absence of clinically apparent oral mucosal alterations. This study evaluated the anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity in 884 BMS patients. METHODS: The blood hemoglobin (Hb) and serum iron, vitamin B12, folic acid, homocysteine, GPCA levels in 884 BMS patients were measured and compared with the corresponding levels in 442 age- and sex-matched healthy control subjects. RESULTS: We found that 175 (19.8%), 143 (16.2%), 42 (4.8%), 20 (2.3%), 170 (19.2%), and 109 (12.3%) BMS patients had blood Hb, serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity, respectively. Moreover, 884 BMS patients had significantly higher frequencies of blood Hb and serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than 442 healthy control subjects (all P-values < 0.005). Of 175 anemic BMS patients, 95 had normocytic anemia, 27 had thalassemia trait-induced anemia, 21 had iron deficiency anemia, 15 had pernicious anemia, 15 had macrocytic anemia other than pernicious anemia, and 2 had microcytic anemia other than iron deficiency anemia and thalassemia trait-induced anemia. Burning sensation of oral mucosa (100.0%), dry mouth (48.1%), numbness of oral mucosa (30.7%), and dysfunction of taste (16.7%) were the four common symptoms in 884 BMS patients. CONCLUSION: BMS patients have significantly higher frequencies of blood Hb and serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than healthy control subjects.

Anemia, hematinic deficiencies, hyperhomocysteinemia, and gastric parietal cell antibody positivity in atrophic glossitis patients with iron deficiency.

BACKGROUND/PURPOSE: Our previous study found that 180 of 1064 atrophic glossitis (AG) patients have iron deficiency. This study assessed whether all AG patients with iron deficiency (so-called ID/AG patients) had iron deficiency anemia (IDA) and evaluated whether the ID/AG patients had significantly higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity than healthy control subjects. METHODS: The blood hemoglobin (Hb) and serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 180 ID/AG patients and 532 healthy control subjects were measured and compared. RESULTS: We found that 180 ID/AG patients had significantly lower mean corpuscular volume (MCV) and lower mean blood Hb and serum iron levels as well as significantly higher mean serum homocysteine level than healthy control subjects (all P-values < 0.001). Moreover, 180 ID/AG patients had significantly higher frequencies of blood Hb (46.1%), serum iron (100.0%), vitamin B12 (8.3%), and folic acid (4.4%) deficiencies, hyperhomocysteinemia (16.1%), and serum GPCA positivity (31.1%) than 532 healthy control subjects (all P-values < 0.001). In addition, of 83 anemic ID/AG patients, 9 (10.8%) had pernicious anemia, 40 (48.2%) had normocytic anemia, 30 (36.2%) had IDA, and 4 (4.8%) had thalassemia trait-induced anemia. CONCLUSION: We conclude that ID/AG patients had significantly higher frequencies of blood Hb, serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than 532 healthy control subjects. Normocytic anemia is the most common type of anemia in ID/AG patients, followed by IDA, pernicious anemia, and thalassemia trait-induced anemia.

Hematinic deficiencies and hyperhomocysteinemia in gastric parietal cell antibody-positive or gastric and thyroid autoantibodies-negative Behcet's disease patients.

BACKGROUND/PURPOSE: Our previous study found that 9 of 63 recurrent aphthous stomatitis (RAS)/Behcet's disease (BD) patients have serum gastric parietal cell antibody (GPCA) positivity. This study assessed whether serum GPCA positivity or RAS/BD itself was a significant factor causing hematinic deficiencies and hyperhomocysteinemia in GPCA-positive RAS/BD (GPCA+RAS/BD) or gastric and thyroid autoantibodies-negative RAS/BD (Abs-RAS/BD) patients. METHODS: The mean blood hemoglobin (Hb), iron, vitamin B12, folic acid, and homocysteine levels were measured and compared between any two of three groups of 9 GPCA+RAS/BD patients, 41 Abs-RAS/BD patients, and 126 healthy control subjects. RESULTS: GPCA+RAS/BD patients had significantly lower mean blood Hb (for men only), iron (for men only), and vitamin B12 levels as well as a significantly higher mean serum homocysteine level than 126 healthy control subjects. Moreover, GPCA+RAS/BD patients had significantly greater frequencies of blood Hb, iron, and vitamin B12 deficiencies and of hyperhomocysteinemia than healthy control subjects. GPCA+RAS/BD patients did have a significantly lower mean serum vitamin B12 level and a significantly higher mean serum homocysteine level as well as significantly greater frequencies of vitamin B12 deficiency and of hyperhomocysteinemia than Abs-RAS/BD patients. Moreover, Abs-RAS/BD patients did have significantly lower mean blood Hb, iron, and folic acid levels and significantly greater frequencies of blood Hb and iron deficiencies than healthy control subjects. CONCLUSION: The GPCA is a major factor causing vitamin B12 deficiency and hyperhomocyteinemia in GPCA+RAS/BD patients. RAS/BD itself does play a significant role in causing anemia and hematinic deficiencies in both GPCA+RAS/BD and Abs-RAS/BD patients.

Hematinic deficiencies, hyperhomocysteinemia, and gastric parietal cell antibody positivity in atrophic glossitis patients with macrocytosis.

BACKGROUND/PURPOSE: Macrocytosis is defined as having the mean corpuscular volume (MCV) â‰§ 100 fL. This study evaluated whether 41 atrophic glossitis (AG) patients with macrocytosis had significantly higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity than 532 healthy control subjects or 1064 AG patients. METHODS: Complete blood count, serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 41 AG patients with macrocytosis, 1064 AG patients, and 532 healthy control subjects were measured and compared. RESULTS: We found that 73.2%, 22.0%, 73.2%, 4.9%, 80.5%, and 56.1% of 41 AG patients with macrocytosis were diagnosed as having blood hemoglobin, iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity, respectively. Moreover, 41 AG patients with macrocytosis had significantly higher frequencies of blood hemoglobin and serum vitamin B12 deficiencies, hyperhomocysteinemia, and serum GPCA positivity than 532 healthy control subjects or 1064 AG patients (all P-values < 0.001). In addition, 41 AG patients with macrocytosis also had significantly higher frequencies of serum iron and folic acid deficiencies than 532 healthy control subjects (both P-values < 0.001). Pernicious anemia was found in 22 AG patients with macrocytosis. CONCLUSION: There are significantly higher frequencies of anemia and serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity in AG patients with macrocytosis than in healthy control subjects. AG patients with macrocytosis also have significantly higher frequencies of blood hemoglobin and serum vitamin B12 deficiencies, hyperhomocysteinemia, and serum GPCA positivity than AG patients.

Hematinic deficiencies and hyperhomocysteinemia in gastric parietal cell antibody-positive or gastric and thyroid autoantibodies-negative atrophic glossitis patients.

BACKGROUND/PURPOSE: Our previous study found that 177 of 1064 atrophic glossitis (AG) patients have serum gastric parietal cell antibody (GPCA) positivity only (so-called GPCA+AG patients). This study assessed whether serum GPCA positivity or AG itself was a significant factor causing hematinic deficiencies and hyperhomocysteinemia in GPCA+AG or GPCA-negative, thyroglobulin antibody (TGA)-negative, and thyroid microsomal antibody (TMA)-negative AG (GPCAÖ¾TGAÖ¾TMAÖ¾AG) patients. METHODS: The mean blood hemoglobin (Hb), iron, vitamin B12, folic acid, and homocysteine levels were measured and compared between any two of three groups of 177 GPCA+AG patients, 476 GPCAÖ¾TGAÖ¾TMAÖ¾AG patients, and 532 healthy control subjects. RESULTS: GPCA+AG patients had significantly lower mean blood Hb and iron (for women only) levels and a significantly higher mean serum homocysteine level than healthy control subjects. Moreover, GPCA+AG patients had significantly greater frequencies of blood Hb, iron, and vitamin B12 deficiencies and hyperhomocysteinemia than healthy control subjects. GPCA+AG patients have a lower mean serum vitamin B12 level and a significantly higher mean serum homocysteine level as well as significantly greater frequencies of vitamin B12 deficiency and hyperhomocysteinemia than GPCAÖ¾TGAÖ¾TMAÖ¾AG patients. Moreover, GPCAÖ¾TGAÖ¾TMAÖ¾AG patients did have significantly lower mean blood Hb and iron levels and significantly greater frequencies of blood Hb, iron, vitamin B12, and folic acid deficiencies and hyperhomocysteinemia than healthy control subjects. CONCLUSION: The GPCA is a major factor causing vitamin B12 deficiency and hyperhomocyteinemia in GPCA+AG patients. AG itself does play a significant role in causing anemia, hematinic deficiencies, and hyperhomocysteinemia in both GPCA+AG and GPCAÖ¾TGAÖ¾TMAÖ¾AG patients.

Gastric parietal cell and thyroid autoantibodies in patients with atrophic glossitis.

BACKGROUND/PURPOSE: Gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) are organ-specific autoantibodies. This study mainly assessed the frequencies of presence of serum GPCA, TGA, and TMA in atrophic glossitis (AG) patients. METHODS: Serum GPCA, TGA, and TMA levels were measured in 1064 AG patients and in 532 age- and sex-matched healthy control subjects. RESULTS: We found that 26.7%, 28.4%, and 29.8% of 1064 AG patients and 2.3%, 2.1%, and 2.6% of 532 healthy control subjects had the serum GPCA, TGA, and TMA positivities, respectively. AG patients had a significantly higher frequency of GPCA, TGA, or TMA positivity than healthy control subjects (all P-values < 0.001). We also found that 67 (6.3%), 181 (17.0%), and 340 (32.0%) AG patients and 3 (0.6%), 10 (1.9%), and 8 (1.5%) healthy control subjects had the presence of three (GPCA + TGA + TMA), two (GPCA + TGA, GPCA + TMA, or TGA + TMA), or one (GPCA only, TGA only, or TMA only) organ-specific autoantibody in their sera, respectively. Of 373 TGA/TMA-positive AG patients whose serum thyroid-stimulating hormone (TSH) levels were measured, 78.6%, 8.0%, and 13.4% of these TGA/TMA-positive AG patients had normal, lower, and higher serum TSH levels, respectively. CONCLUSION: Approximately 55.3% of 1064 AG patients have serum GPCA/TGA/TMA positivity. Because part of GPCA-positive AG patients may develop pernicious anemia, autoimmune atrophic gastritis, and gastric carcinoma, and part of TGA/TMA-positive AG patients may have thyroid dysfunction such as hyperthyroidism and hypothyroidism, these autoantibody-positive AG patients should be referred to medical doctors for further management.

Recurrent aphthous stomatitis - Etiology, serum autoantibodies, anemia, hematinic deficiencies, and management.

Recurrent aphthous stomatitis (RAS) is one of the most common oral mucosal diseases characterized by recurrent and painful ulcerations on the movable or nonkeratinized oral mucosae. Clinically, three types of RAS, namely minor, major, and herpetiform types, can be identified. RAS more commonly affects labial mucosa, buccal mucosa, and tongue. Previous studies indicate that RAS is a multifactorial T cell-mediated immune-dysregulated disease. Factors that modify the immunologic responses in RAS include genetic predisposition, viral and bacterial infections, food allergies, vitamin and microelement deficiencies, systemic diseases, hormonal imbalance, mechanical injuries, and stress. Our previous study found the presence of serum gastric parietal cell antibody, thyroglobulin antibody, and thyroid microsomal antibody in 13.0%, 19.4%, and 19.7% of 355 RAS patients, respectively. We also found anemia, serum iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia in 20.9%, 20.1%, 4.8%, 2.6%, and 7.7% of 273 RAS patients, respectively. Therefore, it is very important to examine the complete blood count, serum autoantibody, hematinic, and homocysteine levels in RAS patients before we start to offer treatments for RAS. Because RAS is an immunologically-mediated disease, topical and systemic corticosteroid therapies are the main treatments of choice for RAS.

Anemia, hematinic deficiencies, and hyperhomocysteinemia in gastric parietal cell antibody-positive and -negative atrophic glossitis patients.

BACKGROUND/PURPOSE: Approximately 27% of atrophic glossitis (AG) patients have the serum gastric parietal cell antibody (GPCA) positivity. This study assessed whether the serum GPCA or AG itself was a significant factor causing anemia, hematinic deficiencies, and hyperhomocysteinemia in GPCA-positive AG (GPCA+AG) and GPCA-negative AG (GPCA-AG) patients. METHODS: The mean corpuscular volume (MCV) and mean blood hemoglobin (Hb), iron, vitamin B12, folic acid, and homocysteine levels were measured and compared between any two of three groups of 284 GPCA+AG, 780 GPCA-AG patients, and 532 healthy control subjects. RESULTS: Both 284 GPCA+AG and 780 GPCA-AG patients had significantly higher frequencies of microcytosis, macrocytosis, blood Hb, iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia than 532 healthy control subjects. Moreover, 284 GPCA+AG patients had significantly higher frequencies of macrocytosis, vitamin B12 deficiency, and hyperhomocysteinemia than 780 GPCA-AG patients. Sixty-three (22.2%) of 284 GPCA+AG patients and 139 (17.8%) of 780 GPCA-AG patients had anemia. The normocytic anemia (42.9%), pernicious anemia (34.9%), and iron deficiency anemia (15.9%) were the three most common types of anemia in the 63 anemic GPCA+AG patients. Moreover, the normocytic anemia (64.8%), iron deficiency anemia (14.4%), and thalassemia trait-induced anemia (13.7%) were the three most common types of anemia in 139 anemic GPCA-AG patients. CONCLUSION: The disease of AG itself is a significant factor causing anemia, hematinic deficiencies, and hyperhomocysteinemia in both GPCA+AG and GPCA-AG patients. The serum GPCA also plays a significant role in causing macrocytosis, vitamin B12 deficiency, and hyperhomocysteinemia in GPCA+AG patients.

Anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody positivity in atrophic glossitis patients with or without microcytosis.

BACKGROUND/PURPOSE: Microcytosis is defined as having mean corpuscular volume (MCV) < 80 fL. This study evaluated whether 79 atrophic glossitis (AG) patients with microcytosis and 985 AG patient without microcytosis had higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity than 532 healthy control subjects. METHODS: Complete blood count, serum iron, vitamin B12, folic acid, homocysteine, and serum GPCA levels in 79 AG patients with microcytosis, 985 AG patient without microcytosis, and 532 healthy control subjects were measured and compared. RESULTS: We found that 69.6%, 43.0%, 5.1%, 3.8%, 11.4%, and 22.8% of 79 AG patients with microcytosis and 14.9%, 14.8%, 5.3%, 2.1%, 12.0%, and 27.0% of 985 AG patients without microcytosis were diagnosed as having blood hemoglobin, iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity, respectively. Both 79 AG patients with microcytosis and 985 AG patients without microcytosis had significantly higher frequencies of blood hemoglobin, iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than 532 healthy control subjects (all P-values < 0.01). Moreover, 79 AG patients with microcytosis had significantly higher frequencies of blood hemoglobin and iron deficiencies than 985 AG patients without microcytosis. CONCLUSION: There are significantly higher frequencies of anemia, serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity in AG patients with or without microcytosis than in healthy control subjects. AG patients with microcytosis have significantly higher frequencies of blood hemoglobin and iron deficiencies than AG patients without microcytosis.

Glycoprotein B7-H3 overexpression and aberrant glycosylation in oral cancer and immune response.

The incidence and mortality rate of oral cancer continue to rise, partly due to the lack of effective early diagnosis and increasing environmental exposure to cancer-causing agents. To identify new markers for oral cancer, we used a sialylation probe to investigate the glycoproteins differentially expressed on oral cancer cells. Of the glycoproteins identified, B7 Homolog 3 (B7-H3) was significantly overexpressed in oral squamous cell carcinoma (OSCC), and its overexpression correlated with larger tumor size, advanced clinical stage, and low survival rate in OSCC patients. In addition, knockdown of B7-H3 suppressed tumor cell proliferation, and restoration of B7-H3 expression enhanced tumor growth. It was also found that the N-glycans of B7-H3 from Ca9-22 oral cancer cells contain the terminal α-galactose and are more diverse with higher fucosylation and better interaction with DC-SIGN [DC-specific intercellular adhesion molecule-3 (ICAM-3)-grabbing nonintegrin] and Langerin on immune cells than that from normal cells, suggesting that the glycans on B7-H3 may also play an important role in the disease.

Oral lichen planus - Differential diagnoses, serum autoantibodies, hematinic deficiencies, and management.

Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease that occurs more frequently in middle-aged and elderly female patients. Previous studies indicate that OLP is a T-cell dysfunction-induced localized autoimmune disease. Clinically, six types of OLP, namely reticular, papular, plaque-like, atrophic/erosive, ulcerative, and bullous types, can be identified. OLP more commonly affects buccal mucosa, tongue, and gingiva. It always has a bilateral and symmetric distribution of the oral lesions. Plaque-like and atrophic/erosive OLP may be misdiagnosed as oral leukoplakia and oral erythroleukoplakia, respectively. Our previous study found serum autoantibodies in 195 (60.9%) of the 320 OLP patients. Specific serum anti-nuclear, anti-smooth muscle, anti-mitochondrial, gastric parietal cell, thyroglobulin, and thyroid microsomal autoantibodies are present in 28.1%, 8.4%, 1.6%, 26.3%, 21.3%, and 24.4% of 320 OLP patients, respectively. Furthermore, we also discovered that 21.9%, 13.6%, 7.1%, 0.3%, and 14.8% of 352 OLP patients have hemoglobin, iron, vitamin B12, and folic acid deficiencies, and abnormally high serum homocysteine level, respectively. Therefore, it is very important to examine the serum autoantibody, hematinic and homocysteine levels in OLP patients before starting the treatments for OLP patients. Because OLP is an immunologically-mediated disease, corticosteroids are the drugs of choice for treatment of OLP.