Higher serum homocysteine level and frequency of hyperhomocysteinemia in carcinoembryonic antigen-positive or squamous cell carcinoma-antigen-positive oral leukoplakia patients.

BACKGROUND/PURPOSE: Our previous study found significantly lower serum hematinic levels and higher serum homocysteine level as well as higher frequencies of serum hematinic deficiencies and hyperhomocysteinemia in oral leukoplakia (OL) patients than in healthy control subjects. This study evaluated whether carcinoembryonic antigen (CEA)-positive or squamous cell carcinoma-antigen (SCC-Ag)-positive OL patients had significantly lower serum hematinic levels and higher serum homocysteine level as well as significantly higher frequencies of hematinic deficiencies and hyperhomocysteinemia than CEA-negative or SCC-Ag-negative OL patients or healthy control subjects. METHODS: The complete blood count, serum iron, vitamin B12, folic acid, and homocysteine levels in 184 OL patients including 85 CEA-positive, 99 CEA-negative, 25 SCC-Ag-positive, and 159 SCC-Ag-negative OL patients and in 184 age- and sex-matched healthy control subjects were measured and compared. RESULTS: We found that the 85 CEA-positive or 25 SCC-Ag-positive OL patients had a significantly lower mean serum folic acid level and a significantly higher mean serum homocysteine level as well as significantly higher frequencies of serum folic acid deficiency and hyperhomocysteinemia than 184 healthy control subjects. Moreover, the 25 SCC-Ag-positive OL patients had a significantly higher mean serum homocysteine level than the 159 SCC-Ag-negative OL patients. The 85 CEA-positive OL patients had a higher mean serum homocysteine level and a higher frequency of hyperhomocysteinemia than 99 CEA-negative OL patients (marginally significant, P = 0.060). CONCLUSION: CEA-positive or SCC-Ag-positive OL patients tend to have a higher mean serum homocysteine level and a higher frequency of hyperhomocysteinemia than CEA-negative or SCC-Ag-negative OL patients, respectively.

Detecting early-stage breast cancer with GATA3-positive circulating tumor cells.

OBJECTIVE: This case demonstrated the possibility of using GATA3-positive circulating tumor cells (CTCs) to detect early-stage breast cancer (BrC). CASE REPORT: The 86 years old female patient received a mammographic examination with no evidence of malignancy (Breast Imaging Reporting and Data System, (BI-RADS category 2). However, CTC testing on the same day revealed four GATA3-positive CTCs in 4 ml of peripheral blood. Core needle biopsy was performed in the suspicious area even with no evidence of malignant image on breast ultrasound. Pathologic examination showed invasive carcinoma of no special type of the breast. The patient then received an oncoplastic partial mastectomy of right breast and sentinel lymph node biopsy. The surgical staging was cT1N0M0. Post-operation follow-up examination showed absence of GATA3-positive CTCs and the presence of HER2/ER positive CTCs. CONCLUSION: The role of GATA3-positive CTCs as a potential biomarker for early-stage BrC should be explored.

Sclerosing Microcystic Adenocarcinoma Arising from the Tongue: A Case Report and Literature Review.

Sclerosing microcystic adenocarcinoma is a rare and recently characterized cancer that affects the mucosal surfaces of the head and neck without adnexal involvement. Histologically, microcystic adnexal carcinoma of the skin resembles it. It does, however, contain unique characteristics that merit our attention for potential diagnostic errors. Therefore, we present a 48-year-old male with sclerosing microcystic adenocarcinoma of the tongue, along with a full discussion and a brief review of pertinent literature.

Using pan-TRK and RET Immunohistochemistry for the Detection of Fusion Types of Salivary Gland Secretory Carcinoma.

Secretory carcinoma (SC) is a low-grade salivary gland carcinoma characterized by recurrent ETV6 rearrangements. Most cases have ETV6-NTRK3 fusions, while the minority of cases have non-NTRK3 fusions, including ETV6-RET and ETV6-MET. Detection of the fusion partner has become important, as there are TRK or RET inhibitors that may benefit patients with advanced SC. Currently, there are different methods to detect gene rearrangement in SCs, such as next-generation sequencing, reverse transcription-polymerase chain reaction, or fluorescence in situ hybridization. Immunohistochemistry (IHC) has greater accessibility, quick turnaround time, and can serve as a screening tool for confirmatory molecular tests. Pan-TRK and RET antibodies have been used to detect gene fusions in different tumors. Here, pan-TRK and RET IHC assays were performed on 28 salivary gland SCs, including 27 cases with ETV6-NTRK3 and one with ETV6-RET fusion confirmed by fluorescence in situ hybridization. Pan-TRK staining was positive in 26/27 (96.3%) of NTRK3 fusion-positive SCs with a nuclear staining pattern in more than 50% of tumor cells, and negative in the RET-rearranged case. RET IHC showed positive staining in most cases (26/28), but only three cases (including the RET-rearranged case) had diffuse and strong staining. RET IHC can be considered an effective screening test when diffuse/strong reactivity is present in pan-TRK IHC-negative cases. This study showed that pan-TRK staining has high sensitivity and specificity for SC with NTRK3 fusion. Whereas pan-TRK IHC is a useful screening method, further studies are needed to assess the value of RET IHC as a second sequential step.

Anemia, hematinic deficiencies, hyperhomocysteinemia, and gastric parietal cell antibody positivity in burning mouth syndrome 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 770 burning mouth syndrome (BMS) patients with normocytosis (so-called normocytosis/BMS patients) had significantly higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity than 442 healthy control subjects or 884 BMS patients. MATERIALS AND METHODS: Complete blood count, serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 884 BMS patients (including 770 normocytosis/BMS patients) and 442 healthy control subjects were measured and compared. RESULTS: We found that 12.3%, 13.2%, 2.2%, 2.3%, 17.3%, and 10.5% of 770 normocytosis/BMS patients had blood hemoglobin (Hb), iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity, respectively. Furthermore, 770 normocytosis/BMS patients had significantly higher frequencies of blood Hb, iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than 442 healthy control subjects (all P-values < 0.005). On the contrary, 770 normocytosis/BMS patients had significantly lower frequencies of blood Hb and vitamin B12 deficiencies than overall 884 BMS patients (both P-values < 0.01). CONCLUSION: We conclude that there are significantly higher frequencies of anemia, serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity in normocytosis/BMS patients than in healthy control subjects. On the contrary, normocytosis/BMS patients do have significantly lower frequencies of blood Hb and vitamin B12 deficiencies than overall BMS patients.

Higher gastric parietal cell antibody titer significantly increases the frequencies of macrocytosis, serum vitamin B12 deficiency, and hyperhomocysteinemia in patients with burning mouth syndrome.

BACKGROUND/PURPOSE: Our previous study found 109 gastric parietal cell antibody (GPCA)-positive burning mouth syndrome (BMS) patients (so-called GPCA+BMS patients in this study) in a group of 884 BMS patients. This study evaluated whether high-titer (GPCA titer ≥ 160) GPCA+BMS patients had greater frequencies of macrocytosis, anemia, serum iron and vitamin B12 deficiencies, and hyperhomocysteinemia than low-titer (GPCA titer < 160) GPCA+BMS patients or 442 healthy control subjects. MATERIALS AND METHODS: Complete blood count, serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 42 high-titer GPCA+BMS patients, 67 low-titer GPCA+BMS patients, and 442 healthy control subjects were measured and compared. RESULTS: We found that 33.3%, 38.1%, 19.0%, 33.3%, 2.4%, and 57.1% of 42 high-titer GPCA+BMS patients and 10.4%, 25.4%, 14.9%, 6.0%, 1.5%, and 11.9% of 67 low-titer GPCA+BMS patients were diagnosed as having macrocytosis, blood hemoglobin, iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia, respectively. Moreover, both 42 high-titer and 67 low-titer GPCA+BMS patients had significantly greater frequencies of macrocytosis, blood hemoglobin, serum iron and vitamin B12 deficiencies, and hyperhomocysteinemia than 442 healthy control subjects (all P-values < 0.001). In addition, 42 high-titer GPCA+BMS patients also had greater frequencies of macrocytosis, serum vitamin B12 deficiency, and hyperhomocysteinemia than 67 low-titer GPCA+BMS patients (all P-values < 0.01). CONCLUSION: The high-titer GPCA+BMS patients have significantly greater frequencies of macrocytosis, anemia, serum iron and vitamin B12 deficiencies, and hyperhomocysteinemia than healthy control subjects and significantly greater frequencies of macrocytosis, serum vitamin B12 deficiency, and hyperhomocysteinemia than low-titer GPCA+BMS patients.

Anemia, hematinic deficiencies, and hyperhomocysteinemia in burning mouth syndrome patients with thyroglobulin antibody/thyroid microsomal antibody positivity but without gastric parietal cell antibody positivity.

BACKGROUND/PURPOSE: Our previous study found that 222 of 884 burning mouth syndrome (BMS) patients have thyroglobulin antibody (TGA) positivity and/or thyroid microsomal antibody (TMA) positivity but without gastric parietal cell antibody positivity (GPCA-TGA+/TMA+BMS patients). This study mainly assessed whether the serum TGA/TMA positivity was significantly associated with anemia, hematinic deficiencies, and hyperhomocysteinemia in GPCA-TGA+/TMA+BMS patients. MATERIALS AND METHODS: The complete blood count, iron, vitamin B12, folic acid, and homocysteine levels were measured and compared between 222 GPCA-TGA+/TMA+BMS patients and 553 GPCA-negative, TGA-negative, and TMA-negative BMS patients (GPCA-TGA-TMA-BMS patients) or 442 healthy control subjects. RESULTS: We found that 222 GPCA-TGA+/TMA+BMS patients had significantly lower mean corpuscular volume (MCV) and lower blood Hb and serum iron levels than 442 healthy control subjects and significantly lower MCV and lower serum homocysteine levels than 553 GPCA-TGA-TMA-BMS patients. Moreover, 222 GPCA-TGA+/TMA+BMS patients had significantly greater frequencies of microcytosis, macrocytosis, blood Hb and serum iron deficiencies, and hyperhomocysteinemia than 442 healthy control subjects and significantly higher frequency of microcytosis but significantly lower frequency of hyperhomocysteinemia than 553 GPCA-TGA-TMA-BMS patients. However, no significant differences in the frequencies of macrocytosis, blood Hb, serum iron, vitamin B12, and folic acid deficiencies were discovered between 222 GPCA-TGA+/TMA+BMS patients and 553 GPCA-TGA-TMA-BMS patients. CONCLUSION: We conclude that the disease of BMS itself does play a significant role in causing macrocytosis, anemia, hematinic deficiencies, and hyperhomocysteinemia in GPCA-TGA+/TMA+BMS patients. However, the serum TGA/TMA-positivity is not significantly associated with anemia and serum iron, vitamin B12, and folic acid deficiencies in GPCA-TGA+/TMA+BMS patients.

Anemia, hematinic deficiencies, and hyperhomocysteinemia in male and female burning mouth syndrome patients.

Background/purpose: Our previous study found that 19.8%, 16.2%, 4.8%, 2.3%, 19.2%, and 12.3% of 884 burning mouth syndrome (BMS) patients have anemia, serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity, respectively. This study mainly evaluated the anemia, hematinic deficiencies, and hyperhomocysteinemia in 212 male and 672 female BMS patients. Materials and methods: The blood hemoglobin (Hb) and serum iron, vitamin B12, folic acid, homocysteine, GPCA levels in 212 male and 672 female BMS patients were measured and compared with the corresponding levels in 106 male and 336 female healthy control subjects, respectively. Results: We found that 212 male BMS patients had significantly lower mean blood Hb, serum iron, vitamin B12, and folic acid levels and significantly higher mean serum homocysteine levels than 106 male healthy control subjects. Moreover, 672 female BMS patients had significantly lower mean blood Hb and serum iron levels and significantly higher mean serum homocysteine level than 336 female healthy control subjects. In addition, 212 male BMS patients had significantly higher mean blood Hb and serum homocysteine levels, significantly lower mean serum vitamin B12 and folic acid levels, and significantly higher frequencies of folic acid deficiency and hyperhomocysteinemis than 672 female BMS patients. Conclusion: The male BMS patients do have significantly higher mean blood Hb and serum homocysteine levels, significantly lower mean serum vitamin B12 and folic acid levels, and significantly higher frequencies of folic acid deficiency and hyperhomocysteinemis than the female BMS patients.

Desmoplastic tumour-associated stroma versus neural tissue in central nervous system metastasis: effects of different microenvironments on tumour growth.

AIMS: Interactions between tumour cells and extracellular matrix (ECM) are critical in the metastatic cascade. We compared effects of desmoplastic stroma versus neural tissue on central nervous system (CNS) metastasis. METHODS AND RESULTS: Using integrins (ECM receptors), ECM (fibronectin, laminin and collagen IV) and CD31 and vascular endothelial growth factor (VEGF) for angiogenesis, this study examined immunohistochemically 69 consecutive cases of CNS metastases. In contrast to low-level expression in tumour-embedded neural tissue, ECM [fibronectin (71%), laminin γ-1 (79%) and collagen IV (92%)] and CD31-positive microvascular densities (33 versus 4 vessels/field) were significantly richer in desmoplastic tumour stroma, which was present in 90% (53 of 59) of carcinomas, 100% (five of five) of malignant melanomas and 100% (two of two) of sarcomas. Collagen IV expression in tumour stroma was correlated with the expression of fibronectin (P = 0.013) and laminin (P = 0.034) and with infiltrative tumour edges (P = 0.005); fibronectin-positive tumour stroma was correlated with a higher microvascular density (P = 0.015). In addition, tumour cells expressed integrins (∼75%) and laminin (84%) more frequently than VEGF (23%), and tumour expression of laminin was correlated with the presence of desmoplastic stroma (P = 0.006). Interestingly, laminin-positive tumour stroma was a worse prognosticator (P = 0.072). CONCLUSIONS: ECM- and vascular-rich stroma is important in tumour growth, which underlies therapeutic strategies targeting tumour-associated stroma.

Anemia, hematinic deficiencies, hyperhomocysteinemia, and gastric parietal cell antibody positivity in burning mouth syndrome patients with or without microcytosis.

BACKGROUND/PURPOSE: Microcytosis is defined as having mean corpuscular volume <80 fL. This study evaluated whether 68 burning mouth syndrome (BMS) patients with microcytosis and 816 BMS patients without microcytosis had higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity than 442 healthy control subjects. MATERIALS AND METHODS: Complete blood count and serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 68 BMS patients with microcytosis, 816 BMS patients without microcytosis, and 442 healthy control subjects were measured and compared. RESULTS: We found that 73.5%, 44.1%, 4.4%, 2.9%, 13.2%, and 10.3% of 68 BMS patients with microcytosis and 15.3%, 13.8%, 4.8%, 2.2%, 19.7%, and 12.5% of 816 BMS patients without microcytosis had blood hemoglobin, iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity, respectively. Both 68 BMS patients with microcytosis and 816 BMS patients without microcytosis had significantly higher frequencies of blood hemoglobin, iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than 442 healthy control subjects (all P-values < 0.05). Moreover, 68 BMS patients with microcytosis had significantly higher frequencies of blood hemoglobin and iron deficiencies than 816 BMS 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 BMS patients with or without microcytosis than in healthy control subjects. BMS patients with microcytosis have significantly higher frequencies of blood hemoglobin and iron deficiencies than BMS patients without microcytosis.

Review of oral ulcerative lesions in COVID-19 patients: A comprehensive study of 51 cases.

Numerous oral manifestations of COVID-19 have been reported in the literatures. Common oral lesions in COVID-19 patients included ulcerations, xerostomia, dysgeusia, gingival inflammation, and erythema. Among them, oral ulceration is the most frequent finding and is present as various but distinct patterns. Thus, we conducted a comprehensive review of 51 COVID-19 patients with oral ulcerative lesions to further analyze the various oral ulcerative lesions in COVID-19 patients. There were a median age of 41.4 years and a slight female predilection in these patients. Most oral lesions manifested as an aphtha-like ulceration but lack of an evidence of recurrent aphthous stomatitis. Some of them were present as herpetiform ulcerations without HSV infection. Widespread ulcerations accompanied with necrosis were observed in the more severe and immunosuppressed older patients. Although some reported patients were asymptomatic, most of them had systemic symptoms concurring or slightly preceding the oral ulcerative lesions and the latency from the onset of systemic symptoms to oral ulcerative lesions were under 10 days, suggesting that oral ulceration was one of the early symptoms of COVID-19. Therefore, the oral ulcerative lesions may be considered as oral markers for early diagnosis of the underlying COVID-19 infection in the asymptomatic patients.

Anemia, hematinic deficiencies, and hyperhomocysteinemia in serum gastric parietal cell antibody-positive burning mouth syndrome patients without serum thyroid autoantibodies.

BACKGROUND/PURPOSE: Our previous study found that 70 of 884 burning mouth syndrome (BMS) patients have serum gastric parietal cell antibody (GPCA) positivity but without thyroglobulin antibody (TGA) and thyroid microsomal antibody (TMA) (so-called GPCA+TGA-TMA-BMS patients). This study assessed whether these 70 GPCA+TGA-TMA-BMS patients had significantly higher frequencies of macrocytosis, anemia, hematinic deficiencies, and hyperhomocysteinemia than 553 GPCA-negative, TGA-negative, and TMA-negative BMS (GPCA-TGA-TMA-BMS) patients or 442 healthy control subjects. MATERIALS AND METHODS: Complete blood count, serum iron, vitamin B12, folic acid, homocysteine, GPCA, TGA, and TMA levels in 70 GPCA+TGA-TMA-BMS patients, 553 GPCA-TGA-TMA-BMS patients, and 442 healthy control subjects were measured and compared. RESULTS: We found that 15.7%, 28.6%, 20.0%, 11.4%, 2.9%, and 25.7% of 70 GPCA+TGA-TMA-BMS patients and 3.8%, 17.7%, 15.9%, 3.8%, 2.7%, and 20.1% of 553 GPCA-TGA-TMA-BMS patients had macrocytosis, blood hemoglobin, iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia, respectively. Moreover, both 70 GPCA+TGA-TMA-BMS patients and 553 GPCA-TGA-TMA-BMS patients had significantly greater frequencies of macrocytosis, blood hemoglobin, serum iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia than 442 healthy control subjects (all P-values < 0.05). In addition, 70 GPCA+TGA-TMA-BMS patients also had greater frequencies of macrocytosis, anemia, serum vitamin B12 deficiency, and hyperhomocysteinemia than 553 GPCA-TGA-TMA-BMS patients (all P-values < 0.05). CONCLUSION: The GPCA + TGA-TMA-BMS patients have significantly greater frequencies of macrocytosis, anemia, serum iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia than healthy control subjects and significantly greater frequencies of macrocytosis, anemia, serum vitamin B12 deficiency, and hyperhomocysteinemia than GPCA-TGA-TMA-BMS patients.

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

BACKGROUND/PURPOSE: Macrocytosis is defined as having the mean corpuscular volume (MCV) ≥ 100 fL. This study evaluated whether 46 burning mouth syndrome (BMS) patients with macrocytosis had significantly higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity than 442 healthy control subjects or 884 BMS patients. MATERIALS AND METHODS: Complete blood count, serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 46 BMS patients with macrocytosis, 884 BMS patients, and 442 healthy control subjects were measured and compared. RESULTS: We found that 65.2%, 23.9%, 47.8%, 0.0%, 60.9%, and 45.7% of 46 BMS patients with macrocytosis were diagnosed as having blood hemoglobin, iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity, respectively. Moreover, 46 BMS patients with macrocytosis had significantly higher frequencies of blood hemoglobin and serum vitamin B12 deficiencies, hyperhomocysteinemia, and serum GPCA positivity than 442 healthy control subjects or 884 BMS patients (all P-values < 0.001). In addition, 46 BMS patients with macrocytosis also had a significantly higher frequency of serum iron deficiency than 442 healthy control subjects (P < 0.001). Pernicious anemia was found in 15 BMS patients with macrocytosis. CONCLUSION: There are significantly higher frequencies of anemia and serum iron and vitamin B12 deficiencies, hyperhomocysteinemia, and serum GPCA positivity in BMS patients with macrocytosis than in healthy control subjects. BMS patients with macrocytosis also have significantly higher frequencies of anemia, serum vitamin B12 deficiency, hyperhomocysteinemia, and serum GPCA positivity than BMS patients.

Galectin-1-mediated tumor invasion and metastasis, up-regulated matrix metalloproteinase expression, and reorganized actin cytoskeletons.

Galectin-1 (Gal-1) is a beta-galactose-binding lectin; its expression level has been reported to correlate with tumor progression. Gal-1 is highly expressed in the invasive front of primary tumors and in the cancer cells of metastatic lesions in the lymph nodes of patients with oral squamous cell carcinoma. However, the molecular mechanism of Gal-1 in tumor metastasis is not completely clear. We found that increased Gal-1 expression is closely associated with its high levels of invasion in lung adenocarcinoma and oral squamous cell carcinoma cell lines. Knocking down Gal-1 with small interfering RNA in highly invasive cancer cells reduced their invasion levels. Moreover, the invasion ability of poorly invasive cancer cells was significantly increased after Gal-1 overexpression of Gal-1. Mechanism studies revealed that Gal-1 promoted tumor invasion mainly by up-regulating matrix metalloproteinase (MMP)-9 and MMP-2 and by reorganizing actin cytoskeleton. Gal-1 enhanced the activation of Cdc42, a small GTPase and member of the Rho family, thus increasing the number and length of filopodia on tumor cells. Furthermore, Gal-1-overexpressing cells had higher metastatic abilities in tail vein metastasis assays in vivo. We conclude that Gal-1 is involved in tumor invasion and metastasis by increasing MMP expression and reorganizing cytoskeletons in oral cancers and lung adenocarcinoma.

Increase of programmed death-1-expressing intratumoral CD8 T cells predicts a poor prognosis for nasopharyngeal carcinoma.

Intratumoral cytotoxic T lymphocytes are critical for controlling tumor recurrence, and programmed death-1 (PD-1) is a recognized marker of T-cell dysfunction. We analyzed this marker and its binding ligands in nasopharyngeal tumor tissue and non-cancerous nasopharyngeal control tissue to retrospectively evaluate the correlation between its expression and the post-treatment outcome of nasopharyngeal carcinoma patients. Using double immunofluorescence staining, we found that the expression of PD-1 in CD8 T cells in tumor tissue was significantly higher than in control tissue (mean: 28.4 vs 3.9%, P<0.0001). Although the expression rate of PD-1 in intratumoral CD8 cells was not associated with the other clinicopathological parameters examined, the higher expression rate in this subset of T cells significantly correlated with a poorer prognosis of overall survival, disease-free survival, and locoregional recurrence-free survival of the cancer patients (P=0.05, 0.007, and 0.004, respectively). Multivariate analysis confirmed it as an independent risk factor for death, treatment failure, and local recurrence of nasopharyngeal carcinoma. On the other hand, the expression of PD-1 in CD4 T cells and of its ligands in epithelial and stromal cells was not significantly different between tumor and control tissue, and its expression was not associated with clinical outcome of the cancer patients. We propose that PD-1 expression in CD8 cells reflects the selective suppression of cytotoxic lymphocytes in the tumor microenvironment and predicts recurrence of nasopharyngeal carcinoma after conventional therapies.

Loss of E-cadherin and beta-catenin is correlated with poor prognosis of ampullary neoplasms.

BACKGROUND AND OBJECTIVES: Distant metastasis resulting from carcinoma cell detachment from the primary tumor involves modification of adhesion molecules. This study was conducted to examine the correlation of E-cadherin/beta-catenin expression with survival and recurrence in ampullary neoplasms. METHODS: Patients with diagnoses of ampullary neoplasms were enrolled in the study. Demographics, operative findings, and histopathological data were collected by retrospective chart review. Expression of E-cadherin and beta-catenin were detected by immunohistochemistry. RESULTS: A total of 110 patients were enrolled in the study. Preservation of membranous staining of E-cadherin was noted in 41 (37%) patients, aberrant cytoplasmic staining in 48 (44%) patients, and complete loss in 21 (19%) patients. Loss of E-cadherin was associated with pancreatic invasion, recurrence, and poor prognosis. Membranous staining of beta-catenin was noted in 65 (59%) patients, cytoplasmic or nuclear accumulation in 16 (15%) patients, and complete loss in 29 (26%) patients. Loss of beta-catenin expression was associated with tumor markers, ulcerative type, liver metastases, and poor prognosis. Pancreatic invasion, lymph node involvement, and loss of beta-catenin expression were predictors of disease recurrence. CONCLUSIONS: Loss of the E-cadherin/beta-catenin complex is related to poor prognosis in ampullary cancer. Loss of beta-catenin is predictor of recurrence in multivariate analysis.

Elastin in oral connective tissue modulates the keratinization of overlying epithelium.

AIM: One of the most discernable differences between keratinized and non-keratinized oral mucosas is the quantity of elastin they contain in the connective tissues. Whether elastin modulates the keratin expression of oral epithelial cells is unknown. METHODS: Four specimens containing both keratinized and non-keratinized mucosas were processed for immunohistochemical (IHC) stainings for elastin and four keratins. Six keratinized and non-keratinized portions of oral mucosas were dissected and cultured on an organ culture system. Purified elastin and elastase were added separately to the media. After 14 days, the mucosas were examined for four keratin expressions. Cell cultures of keratinized and non-keratinized gingival fibroblasts were established and tested for elastin expression. Oral mucosa equivalents were then engineered and tested for keratin expression. RESULTS: Keratinized epithelium exclusively expressed keratin-1 and -10 (K1/10), while non-keratinized epithelium expressed keratin-4 and -13 (K4/13). Only non-keratinized fibroblasts expressed elastin in cell culture. Both the native and the engineered keratinized gingiva changed phenotypes and expressed K4/13 when treated with exogenous elastin. On the contrary, the native non-keratinized mucosa started to express K1/10 when elastase eradicated inherent elastin. CONCLUSIONS: Our study demonstrated that the elastin in the oral connective tissue is important for the non-keratinized phenotypes of overlaying epithelium.

Clinicopathological study of intraductal carcinoma of the salivary gland, with emphasis on the apocrine type.

Intraductal carcinoma (IC) is a rare salivary gland tumor with low- to intermediate-grade cytological features. It is further classified into intercalated duct type and apocrine type based on its distinct histologic and immunohistochemical expression. Conventional salivary duct carcinoma (SDC) is an aggressive carcinoma with high-grade features and is usually associated with poor prognosis. In this study, immunohistochemistry and mutation analyses (including HRAS/PIK3CA mutations, RET rearrangement, and human epidermal growth factor receptor 2 [HER2] amplification) of 9 ICs (including 3 pure ICs, 6 ICs with invasive carcinoma) and 24 conventional SDCs were performed and the results were compared. Four intercalated duct-type cases were positive for SOX10 and S100 and negative for AR; five apocrine-type cases showed opposite results. All five apocrine-type cases had cysts with relatively circumscribed tumor borders and morphologically mimicking breast low-grade ductal carcinoma in situ or papillary carcinoma. RET fusion is detected in half of the 4 intercalated duct-type IC but not in the apocrine-type or conventional SDC. HER2 amplification was only observed in conventional SDC. The monoclonal antibody (clone RBT-NRAS) against NRAS Q61R is a sensitive and specific marker used for detecting HRAS Q61R mutation in the salivary gland tumors. The apocrine-type IC had different cytological grades, distinct tumor growth patterns, and no evidence of low- to high-grade transition, suggesting that apocrine-type IC should be distinguished from apocrine SDC with an in situ component.

Anemia, hematinic deficiencies, hyperhomocysteinemia, and gastric parietal cell antibody positivity in burning mouth syndrome patients with vitamin B12 deficiency.

BACKGROUND/PURPOSE: Our previous study found that 42 of 884 burning mouth syndrome (BMS) patients have vitamin B12 deficiency. This study assessed whether the vitamin B12-deficient BMS (B12D/BMS) patients had significantly higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity than healthy control subjects and evaluated whether all B12D/BMS patients had pernicious anemia (PA). MATERIALS AND METHODS: The blood hemoglobin (Hb) and serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 42 B12D/BMS patients and 442 healthy control subjects were measured and compared. RESULTS: We found that 42 B12D/BMS patients had significantly lower mean blood Hb and serum iron and vitamin B12 levels as well as significantly higher mean corpuscular volume (MCV) and mean serum homocysteine level than healthy control subjects (all P-values < 0.05). Moreover, 42 B12D/BMS patients had significantly higher frequencies of macrocytosis (52.4%), blood Hb (61.9%) and serum iron (26.2%) and vitamin B12 (100.0%) deficiencies, hyperhomocysteinemia (83.3%), and serum GPCA positivity (42.9%) than 442 healthy control subjects (all P-values < 0.001). Moreover, of 26 anemic B12D/BMS patients, 15 (57.7%) had PA, 5 (19.2%) had macrocytic anemia other than PA, 4 (15.4%) had normocytic anemia, and 2 (7.7%) had thalassemia trait-induced anemia. CONCLUSION: B12D/BMS patients have significantly higher frequencies of macrocytosis, blood Hb and serum iron and vitamin B12 deficiencies, hyperhomocysteinemia, and serum GPCA positivity than healthy control subjects. Although PA is the most common type of anemia in our B12D/BMS patients, only 15 (35.7%) of 42 B12D/BMS patients have PA.