Assessment of angiogenesis using endoglin in salivary gland tumors - An immunohistochemical study.

Background: Endoglin, a co-receptor of transforming growth factor (TGF)-ß1 and TGF-ß2, is indispensable for endothelial cell proliferation and modulation of tumor promotion activities of TGF-ß1. The assessment of neovascularization using endoglin expression has been considered a potential predictor of prognosis in various solid malignancies. Aims and Objectives: To analyze the expression of endoglin by immunohistochemistry in both benign and malignant salivary gland tumors. Materials and Methods: Fifteen cases of benign salivary gland tumors and seventeen cases of malignant salivary gland tumors were included in the study, and immunohistochemistry was performed using anti-CD105 antibody using standard protocol. Results and Conclusion: The study demonstrated that there is increased endoglin expression in malignant tumors as compared to their benign counterparts which is suggestive of increased angiogenic activity in tumor areas and could be responsible for the aggressive behavior of the malignancies. The highest density of endoglin-positive blood vessels was observed in the inflammatory tumor stromal areas. Furthermore, a significant increase in endoglin expression was evident as the grade of malignant salivary gland tumor increased. The results of the study indicate that the increased expression of endoglin in high-grade malignancies contributes to their aggressive nature.

Evaluation of salivary metabolomics in oral leukoplakia and oral squamous cell carcinoma.

BACKGROUND: Metabolomics is the study of metabolome which describes the full repertoire of small molecules, and the analysis of salivary metabolomics may help in identifying tumor-specific biomarkers for early diagnosis and prediction of tumor progression. The aim of the study was to evaluate the clinical utility of salivary metabolites in oral leukoplakia and oral squamous cell carcinoma. METHODS: Salivary metabolomic profile of patients diagnosed with oral leukoplakia (n = 21) and oral squamous cell carcinoma (n = 22) was compared with apparently normal controls (n = 18) using Q-TOF-liquid chromatography-mass spectrometry. MassHunter profile software and Metlin database were used for metabolite identification. ANOVA to identify the regulation of metabolites between the three groups, t test (P < 0.05) to signify the changes between two groups, and chi-square test (P < 0.05) to indicate the presence or absence of metabolites in the study participants of the three groups were performed. RESULTS: Significant upregulation of 1-methylhistidine, inositol 1,3,4-triphosphate, d-glycerate-2-phosphate, 4-nitroquinoline-1-oxide, 2-oxoarginine, norcocaine nitroxide, sphinganine-1-phosphate, and pseudouridine in oral leukoplakia and OSCC was noted. Downregulated compounds in the diseased groups included l-homocysteic acid, ubiquinone, neuraminic acid, and estradiol valerate. CONCLUSION: A range of salivary metabolites were significantly altered in oral leukoplakia and oral squamous cell carcinoma. Further, it is necessary to evaluate the clinical utility of the individual metabolites in preventing malignant transformation of oral leukoplakia and to improve prognosis of oral squamous cell carcinoma.

Oral bacterial flora and oral cancer: The possible link?

Oral cancer exhibits multifactorial etiology with tobacco and alcohol long been implicated as the primary risk factors. In addition, betel nut, dietary factors and poor oral hygiene have also been found to have a role in the etiology of oral cancer. Past research has uncovered a great deal of information regarding the association of exogenous bacteria with cancer. However, our definitive knowledge of the oral commensal bacteria and oral cancer link remains inadequate. In the present article, we hypothesize a causal role for oral bacterial flora in oral cancer although an indirect one. We propose that the normal bacterial flora in conjunction with the already established risk factors such as alcohol consumption may play a role in cancer development. The continued exploration of this topic may aid in better understanding of the pathogenesis of oral cancer thereby helping in appropriate treatment and better prognosis.

In vivo autofluorescence of oral squamous cell carcinoma correlated to cell proliferation rate.

CONTEXT: Loss of cell differentiation and increased cellular proliferative activity during malignant transformation leads to alteration of biochemical content of cells. This is reflected in the fluorescence profile of tissues. AIMS: (1) To evaluate the efficacy of autofluorescence in clinical detection of oral cancer. (2) To correlate it with the rate of cell proliferation by analyzing argyrophilic nucleolar organizer regions (AgNORs). SUBJECTS AND METHODS: Autofluorescence status was studied by devising a visual enhancement system using ultraviolet light, followed by an incisional biopsy. Tissue was sent for fluorescence spectroscopy and analyzed by routine histopathology and AgNORs staining. The obtained results were statistically analyzed using Chi-square test (P < 0.05) and one-way analysis of variance. RESULTS: A statistically significant correlation was seen between autofluorescence (AF) and clinical diagnosis as well as autofluorescence and histopathological diagnosis. The importance of autofluorescence as a screening tool was further supported by a statistically significant correlation between autofluorescence status and cell proliferative rate. CONCLUSION: A preliminary effort was attempted at delving into this relatively unexplored arena of optical biopsy systems through this study. They can be used to monitor treatment and potential complications, surgical margins, detection of nodal metastasis, etc. They can provide a diagnosis noninvasively, in situ, and in real time.

Serum metabolomics in oral leukoplakia and oral squamous cell carcinoma.

CONTEXT: Metabolomics is a core discipline of system biology focusing on the study of low molecular weight compounds in biological system. Analysis of human metabolome, which is composed of diverse group of metabolites, can aid in diagnosis and prognosis of oral squamous cell carcinoma (OSCC). AIM: The aim of the present study is to analyze and identify serum metabolites in oral leukoplakia and OSCC as a potential diagnostic biomarker and a predictor for malignant transformation of oral leukoplakia. SUBJECTS AND METHODS: Serum metabolomic profile of patients diagnosed with oral leukoplakia (n = 21) and OSCC (n = 22) was compared with normal controls (n = 18) using quadrupole time of flight-liquid chromatography-mass spectrometry. MassHunter profile software was used for metabolite identification, and statistical analysis to assess the variation of the metabolites was performed using Mass Profiler Professional software. Statistical significance between the three groups was expressed using ANOVA (P < 0.05), and intergroup comparison was done using Student's t-test (P < 0.05). RESULTS: Significant upregulation of estradiol-17-beta-3-sulfate, L-carnitine, 5-methylthioadenosine (MTA), 8-hydroxyadenine, 2-methylcitric acid, putrescine, and estrone-3-sulfate was seen in oral leukoplakia and OSCC than in normal controls. Furthermore, significant upregulation of 5,6-dihydrouridine, 4-hydroxypenbutolol glucuronide, 8-hydroxyadenine, and putrescine was evident in OSCC group than in oral leukoplakia. CONCLUSION: Upregulation of L-carnitine, lysine, 2-methylcitric acid, putrescine; 8-hydroxyadenine; 17-estradiol; 5,6-dihydrouridine; and MTA suggests their diagnostic potential in oral leukoplakia and OSCC. Further, a significant upregulation of putrescine, 8-hydroxyadenine, and 5,6-dihydrouridine in OSCC than in oral leukoplakia indicates their potential role in predicting the malignant transformation of oral leukoplakia.

Extracellular matrix in oral squamous cell carcinoma: Friend or foe?

BACKGROUND: Oral squamous cell carcinoma (OSCC) primarily spreads through direct invasion and/or lymphatic route. During the invasion, tumor cells break through the basement membrane, penetrate the connective tissue to interact with the extracellular matrix (ECM). An attempt was made to evaluate the connective tissue changes in different grades of OSCCs and their influence in predicting the biological behavior of these tumors. MATERIALS AND METHODS: A total of 30 histologically proven cases comprising 5 normal mucosa, 10 well-differentiated OSCC's, 10 moderately differentiated OSCC's, and 5 poorly differentiated OSCC's were examined for the presence of any ECM changes by using special stains. Interpretation of staining intensity was carried out and statistically analyzed. RESULTS: Van Gieson stain showed abundant thick collagen fibers, dispersed collagen fibers, thin few dispersed collagen fibers in well-, moderately- and poorly-differentiated OSCC's, respectively. Verhoeff's Van-Gieson showed negative staining for elastic fibers around tumor islands in different grades of OSCCs. PAS stain showed moderate staining for glycoprotein in well-differentiated OSCC and negative in moderately and poorly differentiated cases. Picrosirius red stain showed Type 1 collagen fibers in well and moderately differentiated OSCC cases and Type 3 collagen fibers in poorly differentiated cases. CONCLUSION: The observations of this study revealed altered staining reactions of the collagenous stroma and glycoproteins suggesting that tumor cells may release certain enzymes that play a role in the manipulation of ECM to enhance their own survival.

Spindle Cell Carcinoma of the Mandibular Gingiva - A Case Report.

Spindle cell carcinoma is a malignancy of epithelial origin often mimicking its mesenchymal counterpart thus posing a diagnostic challenge. It is a rare biphasic malignant tumour mostly encountered in the upper aerodigestive tract. The chief differential diagnoses of spindle cell carcinoma are true superficial sarcomas and they especially need to be differentiated from fibrosarcoma. This presentation reports a spindle cell carcinoma of the gingiva and highlights the difficulties encountered in the diagnosis. It also emphasizes the importance of accurate and thorough diagnosis of malignant spindle cell lesions to determine the appropriate therapeutic modality.

Burkitt's lymphoma of maxillary gingiva: A case report.

Burkitt's lymphoma (BL) is an aggressive form of non-Hodgkin's B-cell lymphoma with three variants namely endemic, sporadic, and immunodeficiency-associated types. It is endemic in Africa and sporadic in other parts of the world. While the endemic form is widely reported to occur in early childhood and commonly involves the jaw bones, the sporadic form typically presents as an abdominal mass. This presentation reports a rare case of sporadic form of BL clinically manifesting as a generalized gingival enlargement in an immunocompetent adult male which demonstrated an aggressive behavior. The patient reported with a prominent anterior gingival swelling of 6 mo duration which slowly enlarged in size and associated with multiple lymph node involvement. Microscopic examination of the lesion using H, E and immunohistochemical diagnosis confirmed the diagnosis as BL. The patient succumbed to the disease before any therapy could be instituted. Since a wide array of causes can be attributed to gingival enlargements, it is necessary to consider malignancies as one of the important differential diagnosis so as to facilitate the need for appropriate diagnosis and prompt treatment.

Toluidine blue: A review of its chemistry and clinical utility.

Toluidine blue is a basic thiazine metachromatic dye with high affinity for acidic tissue components, thereby staining tissues rich in DNA and RNA. It has found wide applications both as vital staining in living tissues and as a special stain owing to its metachromatic property. Toluidine blue has been used in vivo to identify dysplasia and carcinoma of the oral cavity. Use of toluidine blue in tissue sections is done with the aim to highlight components, such as mast cells granules, mucins, and cartilage. This article provides an overview on chemistry, technique, and the various applications of toluidine blue.

Nitric oxide and oral cancer: a review.

Nitric oxide (NO), a short-lived, endogenously produced gas, plays key role in various physiological as well as pathological processes. NO-inducing cell signaling events within the cell producing it and the diffusibility of it in other cells have led to the discovery of various physiological functions of NO including vasodilation, respiration, cell migration, immune response and apoptosis. On the other hand, excessive and unregulated NO synthesis has been implicated in many pathophysiological conditions including cancer. Research on NO, during the past few years is one of the growing areas in cancer biology. The high incidence of oral cancer and precancer has been linked with habits of tobacco chewing and smoking and NO has been said as the "messenger of death" in tobacco related diseases. NO seems to play a part in various stages of carcinogenesis from initiation to progression. However, there is considerable controversy and confusion in understanding its role in cancer biology. It is said to have both, tumoricidal as well as tumor promoting effects and these depend on its timing, location and concentration. Further, NO has also been shown to have antitumor, chemopreventive and therapeutic abilities. Here is an overview in which efforts are made to understand the role of this molecule in oral carcinogenesis.