P-Cadherin and WNT5A expression in assessment of lymph node metastasis in oral squamous cell carcinoma.

BACKGROUND: Oral cancer progression is a multi-step process in which adhesion molecules play a pivotal role in the development of recurrent, invasive, and distant metastasis. The aim of this study was to adopt prognostic biomarkers to assess the lymph node metastasis of OSCC that will facilitate in deciding the treatment modality by the surgeons. OBJECTIVES: The objectives of the study were to assess the biological behaviour of OSCC by correlating the expression levels of P-Cadherin and WNT5A immunohistochemically. METHODS: A total of 60 selected OSCCs cases (lymph node metastasis n = 30, non-metastatic n = 30) and 10 normal healthy controls were quantitatively and qualitatively analysed by immunohistochemistry for P-Cadherin and WNT5A. A survival analysis was also performed. RESULTS: The expression levels of P-Cadherin and WNT5A in OSCC groups were statistically significant between metastatic and non-metastatic groups (p < 0.001). P-Cadherin and WNT5A expression in metastatic (lymph node metastasis) and non-metastatic cases showed a significant correlation coefficient of 0.753 at (p < 0.01). The present study also found that the aberrant expression (high) of P-Cadherin was associated with diminished survival of patients with metastatic OSCC. CONCLUSION: The present study demonstrated the aberrant expression of P-Cadherin and WNT5A could serve as important prognosticator in OSCC. CLINICAL RELEVANCE: P-Cadherin and WNT5A could be used as significant predictors of disease outcome.

Nanopore Sequencing Technology in Oral Oncology: A Comprehensive Insight.

AIM: To review the principles and application of Nanopore Sequencing Technology (NPST) in oral cancer. BACKGROUND: Oral cancer is a disease caused by aberrations in the genes. Substantial research at the genomic level is still required for in-depth understanding of the molecular mechanism in oral cancer. The advent of the novel nanopore sequencing technique has the potential to detect the alterations at the genomic level. This review highlights nanopore sequencing, its advantages and disadvantages, and how research supports its application in the field of oral oncology. MATERIALS AND METHODS: Web-based search via PubMed database, internet sources using keywords "nanopore sequencing, third-generation sequencing, next generation sequencing, cancer, oral squamous cell carcinoma, genetic, epigenetic, oncogenic viruses" was performed in this review. Original research, reviews, and short discussions published from 2008 to 2020 were included. The findings are discussed with emphasis on common gene mutations, epigenetic alterations, and oncogenic viruses in oral cancer. A brief mention regarding translational nanopore sequencing research in oral cancer and future perspectives is also discussed. RESULTS: The results obtained reveal that cost-effectiveness and rapid turnaround time make nanopore sequencing an enticing platform to resolve the ambiguity of genomes, epigenomes, and transcriptomes. CONCLUSION: The findings will encourage researchers to further adopt NPST in their studies and give an overview of the latest findings of oral squamous cell carcinoma (OSCC) management. To highlight the importance of NPST application in OSCC studies, this paper not only discusses the use of NPST in identifying the behavior of malignancy but also implies the need for further research using this technique. CLINICAL SIGNIFICANCE: The review suggests that nanopore sequencing can be utilized for diagnosis and achieving personalized treatment in each oral cancer patient.

Cytogenetics in Oral Cancer: A Comprehensive Update.

AIM: To evaluate the application of cytogenetic techniques in determining the diagnosis, prognosis, and therapeutics in oral cancer. BACKGROUND: Genetic aberrations that play an important role in oral oncogenesis demand substantial research for in-depth characterization of the tumor. Cytogenetic techniques have the potential to detect these aberrations. This review highlights about various cytogenetic approaches in cancer and how these findings support its application in the field of oral oncology. METHODS: Google scholar search was done for articles on cancer cytogenetics, and in particular, PubMed database was queried for articles published from 2015 to 2020 using keywords cytogenetics, chromosomal aberrations, conventional cytogenetics, karyotyping, banding techniques, molecular cytogenetics, fluorescent in situ hybridization, spectral karyotyping, comparative genomic hybridization, multiplex ligation probe analysis, and next-generation sequencing (NGS) in oral cancer. Abstracts were reviewed, and relevant full text was accessed to extract the cytogenetic findings in oral cancer. RESULTS: Data regarding various cytogenetic approaches from conventional to molecular techniques have been published in oral cancer. They convey a highly complex cytogenetic finding from gross chromosomal aberrations to specific gene mutations in oral cancer. CONCLUSION: Crucial information in the development and progression of oral cancer is achieved through cytogenetic findings in particular with the molecular cytogenetic techniques. Novel technologies like NGS have emerged in recent years that hold promise in the detection of these alterations more efficiently. CLINICAL SIGNIFICANCE: An appraisal of cytogenetic analysis in oral cancer helps to determine the diagnosis and the most important prognosticators. It assists in building targeted therapies for patient benefit.

Role of cancer stem cells in head-and-neck squamous cell carcinoma - A systematic review.

Targeting cancer stem cell (CSC) subpopulation within the tumor remains an obstacle for specific therapy in head-and-neck squamous cell carcinoma (HNSCC). Few studies in the literature describe a panel of stem cell makers, however a distinct panel has not been put forth. This systematic review aims to enhance the knowledge of additional markers to accurately relate their expression to tumorigenesis, metastasis, and therapy resistance. Databases, including PubMed, Google Scholar, Ebsco, and Science Direct, were searched from 2010 to 2017 using various combinations of the following keywords: "Stem cell markers in HNSCC" and "chemoresistance and radioresistence in HNSCC." Original experimental studies (both in vitro and in vivo) published in English considering stem cell markers in HNSCC, were considered and included. We excluded articles on tumors other than HNSCC, reviews, editorial letters, book chapters, opinions, and abstracts from the analyses. Forty-two articles were included, in which 13 types of stem cell markers were identified. The most commonly expressed CSC markers were CD44, aldehyde dehydrogenase, and CD133, which were responsible for tumorigenesis, self-renewal, and therapy resistance, whereas NANOG, SOX-2, and OCT-4 were involved in metastasis and invasion. Identification of an accurate panel of CSC markers is the need of the hour as nonspecificity of the current markers poses a problem. Further studies with a large sample size would help validate the role of these CSC markers in HNSCC. These CSC proteins can be developed as therapeutic targets for HNSCC therapy, making future treatment modality more specific and effective.

Lipid metabolism in cancer: A systematic review.

Preclinical studies and clinical trials have emphasized the decisive role of lipid metabolism in tumor proliferation and metastasis. This systematic review aimed to explore the existing literature to evaluate the role and significance of the genes and pathways most commonly involved in the regulation of lipid metabolism in cancer. The literature search was performed as per Preferred Reporting Items for Systematic Reviews and Meta-analyses. Approximately 2396 research articles were initially selected, of which 215 were identified as potentially relevant for abstract review. Upon further scrutiny, 62 of the 215 studies were reviews, seminars, or presentations, and 44 were original study articles and were thus included in the systematic review. The predominant gene involved in lipid metabolism in cancer was stearoyl-coenzyme A desaturase 1 (SCD1), followed by fatty acid synthase (FASN). The pathway most commonly involved in lipid metabolism in cancer was the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, followed by the mitogen activated protein kinase (MAPK) pathway. SCD1 and FASN play significant roles in the initiation and progression of cancer and represent attractive targets for potentially effective anti-cancer treatment strategies. The regulation of cancer metabolism by the Akt kinases will be an interesting topic of future study.

Immunohistochemical expression of Tazarotene-induced Gene 3 in oral squamous cell carcinoma.

BACKGROUND: The prognosis of hyperproliferative skin lesions, such as psoriasis, basal cell carcinoma, and non-melanoma skin cancers, is significantly benefited from the levels of tazarotene-induced gene-1 (TIG3) expression and subsequent treatment with tazarotene. Such observations suggest that TIG3 could be used as a biomarker for apoptosis, differentiation, and proliferation. The current study aimed to evaluate the expression of TIG3 in normal oral mucosa (NOM) and oral squamous cell carcinoma (OSCC) compared with normal skin (NS) and skin squamous cell carcinoma (SSCC) using immunohistochemistry. METHODS: Seventeen cases each of SSCC, OSCC, NOM, and NS were evaluated. Each section was immunohistochemically stained with a rabbit polyclonal TIG3 antibody. The entire procedure was blinded and evaluated by 5 observers. Statistical analysis was performed using the chi-square test. RESULTS: There was a significant decrease in TIG3 protein expression in OSCC and SSCC compared with that in NOM and NS (P = 0.008). The progressive loss of expression was observed as the grade of both malignancies increased. However, there was no significant difference in the expression among the normal tissue groups and within SCC groups of similar grades. CONCLUSION: The present study suggests that the loss of TIG3 is an important event in carcinogenesis. TIG3 acts as a regulator of keratinocyte proliferation and terminal differentiation. Therefore, TIG3 could be a potential biomarker to differentiate aggressive and non-aggressive neoplasms.

Molecular pathways of oral cancer that predict prognosis and survival: A systematic review.

Several genes and pathways associated with oral squamous cell carcinoma (OSCC) are significant in terms of early detection and prognosis. The objective of this literature review is to evaluate the current research on molecular pathways and genes involved in oral cancer. Articles on the genes involved in oral cancer pathways were evaluated to identify potential biomarkers that can predict survival. In total, 36 articles were retrieved from internet databases, including EBSCO Host, Google Scholar, PubMed, and Science Direct, using the keywords "biomarker of oral cancer," "pathways of oral cancer," "genes involved in oral cancer," and "oral cancer pathways." A total of 36 studies related to OSCC were chosen. Most of the studies used cell lines, while others used archival tissues, few studies followed up the cases. Three major interlinked pathways found were the nuclear factor kappa B (NF-kB), PI3K-AKT, and Wnt pathways. The commonly mutated genes were cyclin D1 (CCND1), Rb, p53, FLJ10540, and TC21. The NF-kB, PI3K-AKT, and Wnt pathways are most frequently involved in the molecular pathogenesis of oral cancer. However, the CCND1, Rb, p53, FLJ10540, and TC21 genes were found to be more accurate in determining patients' overall survival. Polymerase chain reaction, immunohistochemistry, and immunoblotting were the commonly used detection methods.

Digital microscopy: A routine mandate in future? A leaf out of Covid-19 pandemic laboratory experience.

The COVID-19 pandemic has brought out lot of changes among the way people and organisations function. It has also reduced social gatherings and hence social relations considerably, forcing people to adjust to new ways of work and life. An outstanding difference between the current COVID-19 pandemic and previous epidemics or pandemics is the increased availability and use of technology currently, which has been validated by various reports from across the globe. Thus, even with the ensuing pandemic, lockdown and decreased social gatherings, with the technology support we have devised ways to keep in contact with friends, family and work place, so as to continue our lives. Social distancing guidelines and regulations have put pressure on a great many organisations to find new ways of keeping employees and students connected while working remotely. For more deskbound occupations and roles, this can be relatively straightforward, but it is challenging if not impossible for lab-based quality control, research and study. The answer to this is digital remote microscopy which enables sharing of data online, carrying out collaborative work through multi-viewing in real time and facilitates remote training functions.

A multicentric case study of fibroblastic and myofibroblastic oral spindle cell lesions.

Context: Spindle cell lesions comprise a vast plethora of benign and malignant lesions with similar clinical and radiographic features. Their overlapping histopathologic features ensure a diagnostic dilemma. Aim: The current multicentric study aims to delineate fibroblastic and myofibroblastic oral spindle cell lesions based on cytomorphology and comprehensive immunohistochemical analysis. Settings and Design: The experimental study was conducted at MS Ramaiah University of Applied Sciences, Bangalore, and All India Institute of Applied Sciences, Delhi. Methods and Material: A comprehensive histological scoring criteria and panel of immunohistochemical makers (STAT6, CD31, CD34, S100, SMA, vimentin, pan-CK, HHF-35, Ki67, ALK, desmin, HMB-45, SATB2, ERG, EMA and CD99) were employed concurrently for the first time for fibroblastic and myofibroblastic oral spindle cell lesions. The data obtained was tabulated and studied. Statistical Analysis Used: NA. Results: Using cytological scoring criteria and panel of immunohistochemical makers, the cases analysed and characterized were desmoplastic fibroma, fibrosarcoma, leiomyosarcoma, nodular fasciitis, neurofibroma and epithelioid inflammatory myofibroblastic sarcoma (EIMS). Conclusions: The diagnostic strategies need to be upgraded for the diagnosis of spindle cell lesions. Emphasis must be placed on cytomorphology, an immunohistochemistry (IHC) panel of markers is imperative for the accurate diagnosis of fibroblastic and myofibroblastic oral spindle cell lesions.

Micrometastasis detection using modified papanicolaou stain in nodal tissues of oral squamous cell carcinoma - A histological study.

CONTEXT: Cervical lymph node metastasis is the most important prognostic factor in Squamous Cell Carcinoma of Head and Neck (SCCHN). Detection and evaluation of micro-metastasis forms the basis for diagnosis, staging, treatment options and prognosis. Lymph node prognostic factors are extremely important for the survival and recurrence in the patient. Assessing lymph node metastasis in the absence of clinical enlargement is challenging. AIM: To evaluate micrometastasis and individual tumor cells (ITC) in regional lymph nodes of oral squamous cell carcinoma (OSCC) by modified papanicolaou (PAP) stain and re-evaluate the tumor staging. SETTINGS AND DESIGN: The retrospective study was executed at MS Ramaiah University of Applied Sciences. METHODS AND MATERIALS: The current study constituted a total of 40 lymph nodes from OSCC patients, metastatic (n=20) and non-metastatic lymph nodes (n=20). All sections were stained with H & E followed by modified PAP stain. Modified PAP was used for identification of micrometastasis deposits. STATISTICAL ANALYSIS USED: The Chi square test was employed to analyze significance. RESULTS: Modified PAP stain proved to be more accurate (p = 0.006) than H and E stain in detecting micrometastasis which accounted for 15% of non-metastatic lymph node sections used in our study. CONCLUSION: Special stain like modified PAP stain is valuable and sensitive in detecting micro-metastasis over H and E stain. Detection of micrometastasis in OSCC patients is advantageous for the patient as it influences staging, it modifies the treatment plan in terms of both radiotherapy and chemotherapy.

Role of Nanozymes in Oral Cancer the Road Ahead.

Oral cancer is a result of diverse interactions in the tumor microenvironment (TME), genetic alterations along with associated risk factors such as lifestyle and microbial infections. Various modalities are employed in the diagnosis and therapeutics of oral cancer. Nanozymes which are artificial enzymes have a great potential in the diagnostic and therapeutic approach of tumors. They have enormous advantages compared to natural enzymes and possess inherent biological and physical properties. A web-based search was performed via the Google scholar, PubMed database, Web of Science with keywords nanozymes, nanoparticles in cancer and oral cancer. The other keywords used were diagnosis, therapy, TME, microbiome, molecular alterations, biosensor, targeted therapy, imaging and tissue regeneration. Original research studies, reviews, case reports published from 2012 to 2022 were included to appraise different subsections. An absolute lack of literature on nanozymes was observed in oral cancer. The present review is the first attempt to describe the role and application of nanozymes in oral cancer by correlating its outcome in tumor biology and biomedical research. Rapid development of nanotechnology has created a paradigm shift in cancer diagnosis and therapeutics. Nanozymes with novel designs can be anticipated in the future in oral cancer management. Supplementary Information: The online version contains supplementary material available at 10.1007/s11244-022-01729-9.

Immunology of Oral Squamous Cell Carcinoma-A Comprehensive Insight with Recent Concepts.

This review aims to understand the concept of oral cancer immunology through the notion of immune profiling, immunoediting and immunotherapy, and to gain knowledge regarding its application for the management of oral cancer patients. Oral cancer is an immunogenic tumor where the cells of the tumor microenvironment play an important role in tumorigenesis. Understanding the mechanism of these modulations can help design immunotherapeutic strategies in oral cancer patients. This article gives an overview of immunomodulation in the oral cancer tumor microenvironment, with concepts of immune profiling, immunoediting and immunotherapy. English literature searches via Google Scholar, Web of Science, EBSCO, Scopus, and PubMed database were performed with the key words immunology, tumor microenvironment, cells, cross talk, immune profiling, biomarkers, inflammation, gene expression, techniques, immunoediting, immunosurveillance, tumor escape, immunotherapy, immune checkpoint inhibitors, vaccines in cancer, oral cancer, and head and neck cancer. Original research articles, reviews, and case reports published from 2016-2021 (n = 81) were included to appraise different topics, and were discussed under the following subsections. Literature published on oral cancer immunology reveals that oral cancer immune profiling with appropriate markers and techniques and knowledge on immunoediting concepts can help design and play an effective role in immunotherapeutic management of oral cancer patients. An evaluation of oral cancer immunology helps to determine its role in tumorigenesis, and immunotherapy could be the emerging drift in the effective management of oral cancer.

Erosive Effect of Acidic Beverages and Dietary Preservatives on Extracted Human Teeth-An In Vitro Analysis.

OBJECTIVES: Frequent consumption of acidic beverages and dietary preservatives in younger generation, diet-conscious (celebrities), and obese individuals have a rapid impact on demineralization of the teeth. An attempt was made to analyze the erosive potential of various acidic beverages. MATERIALS AND METHODS: One hundred and ninety extracted human permanent teeth were sectioned longitudinally, pre-weighed, randomly grouped, and placed in nine acidic beverages (200 mL) with predetermined pH, i.e., three commercially available fruit juices, three carbonated drinks, and three dietary preservatives. STATISTICAL ANALYSIS: The sectioned specimens (n = 10) were analyzed at time intervals of 12, 24, 48, and 96 days. Mean weight loss was calculated, and surface changes were assessed under a stereomicroscope. The demineralization pattern and microscopic changes were observed under a compound and polarizing microscope. One-way analysis of variance test followed by Tukey's post-hoc analysis was employed. RESULTS: Overall the maximum demineralizing effect was caused by vinegar and apple cider. In the fruit juices category, lemon juice induced significant changes, while in the carbonated drinks category Coca-Cola induced the maximum changes and in the category of food preservatives vinegar induced the maximum changes. Severe discoloration was seen with respect to Coca-Cola followed by Mountain Dew (carbonated drink). CONCLUSION: The present study is unique as three different types of microscopes have been employed and both dentin and enamel of permanent teeth have been analyzed. In addition, the effect of dietary preservatives on hard tissues was evaluated. Oral health educators can reinforce important practices such as decreasing the frequency of consumption and time duration of beverage contact with the teeth. Also, the use of mouth rinses and buffering agents after the consumption of dietary beverages can be advocated along with regular fluoride application for those who are regular consumers.

Alternate Special Stains for the Detection of Mycotic Organisms in Oral Cyto-Smears-A Histomorphometric Study.

In the wake of the COVID-19 pandemic, fungal infections of the maxillofacial region have become prevalent, making their accurate diagnosis vital. Histopathological staining remains a simple, cost-effective technique for differentiation and diagnosis of the causative fungal organisms. The present study aims to evaluate the staining efficacy of Periodic Acid-Schiff (PAS), Alcian Blue, Safranin-O and Gomori's Methenamine Silver (GMS) on fungal smears. This research work also attempts to study the morphometric characteristics of Candida albicans, Aspergillus flavus, Rhizopus oryzae. Candida albicans, Aspergillus flavus and Rhizopus oryzae, 10 smears each, were stained using PAS, Alcian Blue, Safranin-O and GMS. The morphological characteristics and staining efficacy were examined, and semi-quantitative scoring was performed. Candida albicans, Aspergillus flavus and Rhizopus oryzae were stained for the first time with Safranin-O. The morphometric traits were then analyzed using an image analysis software. Safranin-O provided the most reliable staining efficacy amongst the stains and optimum morphological definition for all three organisms. Safranin-O was found to be superior to PAS and GMS, ensuring detection of even the most minute mycotic colonies. The hyphae of Aspergillus flavus to be the largest, and the spores and fruiting body of Rhizopus oryzae were found to be the largest amongst the three organisms compared. Early and accurate diagnosis of fungal infections can significantly reduce morbidity in orofacial fungal infections.

Natural stain (Kumkum) formulated by the extract of Curcuma aromatica and slaked lime in histostaining of oral tissues: An observational study.

BACKGROUND: The pharmacological actions of Curcuma aromatica (wild turmeric) such as anti-inflammatory, antitumor, antifungal, antimicrobial and wound healing have been recognized since ages. However, its role as a natural histological stain has not been explored till date. AIM: To evaluate the efficacy of natural substance-Kumkum prepared from the extract of C. aromatica and slaked lime in staining the biopsied oral tissues. MATERIALS AND METHODS: A cohort study that used 60 formalin fixed paraffin embedded soft and hard tissue specimens from institutional archives were subjected to sectioning and stained using Kumkum and hematoxylin and eosin (H and E). The slides were evaluated for their staining efficacy and results were statistically analyzed using Wilcoxon signed-rank test and Independent 't' test. RESULTS: The mean of the overall parameters assessed for staining efficacy did not show statistically significant difference between the study groups in normal and pathological specimens for tooth (P = 0.410 and 0.484), bone (P = 0.133 and 0.157) and soft tissues (P = 0.186 and 0.113), respectively. This suggests that Kumkum staining efficacy is equivalent to that of routine H and E for oral tissues. Structures such as dentinoenamel junction, dentinal tubules, incremental lines of cementum, reversal and resting lines, osteocytic canaliculi, mature and immature bone could be appreciated better in Kumkum stained slides, thereby rendering a special staining property to Kumkum stain. CONCLUSION: To our knowledge, this study is the first of its kind to have used Kumkum stain obtained from C. aromatica for the differentiation of the components of tooth, bone and soft tissue structures in histostaining of oral tissues. The naturally prepared Kumkum stain possesses dual staining property both in routine and differential staining. This facilitates diagnosis of fibro-osseous lesions, bony, collagen and muscular pathologies. The natural stain also finds application in forensic odontology for age estimation.

PECAM-1 overexpression signifies aggressive biologic behavior of oral lichen planus - A pilot study.

CONTEXT: The etiopathogenesis of oral lichen planus (OLP) is still debatable. According to literature, many studies have illustrated OLP as a T-cell-mediated chronic autoimmune disease. Currently, there is increased evidence of chronic inflammation in OLP and its association with vascular adhesion molecules (VAMs). AIM: The aim of this study was to evaluate the expression of VAM (PECAM-1) in OLP. SETTING AND DESIGN: Tissue samples involved 20 archival cases of histopathologically confirmed OLP (n = 15) and normal mucosa (n = 5) as controls. MATERIALS AND METHODS: The sections were subjected to immunohistochemical analysis using antibody to PECAM-1. Brown staining of the endothelial cells of blood vessels was considered positive. The expression of PECAM-1 in OLP was statistically analyzed using Wilcoxon sign-rank test. RESULTS: The expression of PECAM-1 in OLP was statistically significant when compared with normal mucosa (P < 0.05). A statistically significant difference was also observed in PECAM-1 expression between the reticular type and erosive type of OLP. CONCLUSION: PECAM-1 was found to be overexpressed in OLP; difference in PECAM-1 expression was noted between the reticular and erosive types. The VAMs could be exploited as a possible therapeutic target in OLP to modulate the disease process thereby reducing the dependency on corticosteroids.

Expression of hTERT in Oral Submucous Fibrosis and Oral Squamous Cell Carcinoma - an Immunohistochemical Analysis.

Human telomerase reverse transcriptase enzyme, the catalytic subunit of telomerase are seen to be frequently reactivated in cancers including Oral squamous cell carcinoma (OSCC). Increased hTERT expression have been seen in potentially malignant conditions including Oral submucous fibrosis (OSMF). The aim of the study was to evaluate the expression levels in OSMF, OSCC in the background of OSMF and OSCC using immunohistochemistry and also to correlate hTERT expression with clinicopathologic parameters. A total of 50 histopathologically diagnosed cases of 20 OSMF, 20 OSCC wherein 5 were OSCC in the background of OSMF and 10 Normal oral mucosae were retrieved from the departmental archives and subjected to immunohistochemical analysis of hTERT. The expression of hTERT increased from normal, OSMF, to OSCC with statistically significant differences in mean labelling score (LS). We also found a shift in cellular localization of stain where, normal mucosal tissues showed a nuclear stain unlike OSMF, where combined nuclear and cytoplasmic staining as noted. The tumor cells in OSCC showed predominant cytoplasmic staining. There was no correlation between hTERT expression and clinicopathological parameters of OSMF. However, a significant increase of hTERT expression was seen with increasing histological grading of OSCC. These results suggest the role of hTERT in the early event of malignant transformation of OSMF. Telomerase could be used as a potent diagnostic marker to identify high-risk group of OSMF.

Does microbiome shift play a role in carcinogenesis? A systematic review.

Recent scientific advances have presented substantial evidence that there is a multifaceted relationship between the microbiome and cancer. Humans are hosts to multifarious microbial communities, and these resident microbes contribute to both health and disease. Circulating toxic metabolites from these resident microbes may contribute to the development and progression of cancer. The aim of this systematic review was to evaluate microbiome and microbial shift contribution to the development and progression of cancer. This systematic review provides an analytical presentation of the evidence linking various parts of the microbiota to cancer. Searches were performed in databases such as PubMed, Google Scholar, Scopus, EBSCO, E-Journals and Science Direct from the time of their establishment until May 2018 with the following search terms: cancer or human microbe or cancer and human microbiome AND shift in microbes in cancer. The merged data were assessed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Cochrane's Risk of Bias Tool was used to assess the bias. Initially, 2,691 articles were identified, out of which 60 full-text articles were screened and re-evaluated. Among them, 14 were excluded based on inclusion/exclusion criteria; eventually, 46 articles were included in the systematic review. The reports of 46 articles revealed that microbial shift involving Candida species, Fusobacterium nucleatum, Porphyromonas gingivalis, Helicobacter pylori and Human papilloma virus (HPV) 16 & 18 were most commonly involved in various human cancers. In particular, organisms, such as Candida albicans, Fusobacterium nucleatum, Porphyromonas gingivalis and HPV-16 were found to be more prevalent in oral cancer. The present systematic review emphasizes that the role and diverse contributions of the microbiome in carcinogenesis will provide opportunities for the development of effective diagnostic and preventive methods.

Cocktail of Periodic Acid-Schiff and Papanicolaou: Novel staining technique for the identification of leukemic eosinophils - A pilot study.

BACKGROUND: Tissue eosinophilia may be caused due to reactive, neoplastic or idiopathic reasons. Reactive eosinophils in allergic and inflammatory conditions are transient and recruited from the circulation in response to various stimuli, whereas neoplastic eosinophils of leukemias and hematological malignancies are involved in the pathogenesis of the disease. The differentiation of reactive from neoplastic eosinophils has a serious implication on the treatment and prognosis of diseases. However, both these types of eosinophils display variation in morphology and staining characteristics in routine histopathology leading to a diagnostic dilemma. AIM: The aim of this study is to evaluate the efficacy of special stains for the demonstration of eosinophils in normal/reactive lesions and leukemias. METHODOLOGY: A retrospective study comprising twenty histologically diagnosed cases each of reactive oral lesions and leukemias were obtained from institutional archives. These tissue sections were subjected to staining with routine and special stains - Carbol chromotrope, Congo red, Leishman's stain, Periodic Acid-Schiff-papanicolaou (PAS-PAP) and PAS. Statistical analysis was performed using Pearson's Chi-square test to compare the various parameters in the evaluation of the staining efficacy. RESULTS: Carbol chromotrope and Congo red staining showed increased staining efficacy in normal/reactive eosinophils while PAS-PAP followed by PAS and Leishman's stain showed enhanced features such as homogenicity, specificity, increased staining intensity, enhanced nuclear and cytoplasmic details in leukemic eosinophils. CONCLUSION: Combined PAS-PAP is a novel and cost-effective staining technique in differentiating reactive and leukemic eosinophils. It is significant in recognizing leukemic eosinophils of routine biopsies and alerts the clinician to rule out any underlying malignancies.

Interleukin-1beta and Caspase-3 expression serve as independent prognostic markers for metastasis and survival in oral squamous cell carcinoma.

BACKGROUND: The Indian subcontinent has the highest incidence and prevalence of oral squamous cell carcinoma (OSCC). Inflammation and apoptosis are two emerging hall marks of cancer that might play a significant role in tumorigenesis and metastasis. Concurrent expression of proinflammatory cytokine (IL-1ß) and executioner caspase (Caspase-3) in same OSCC tissue samples has not been reported in an Indian population. OBJECTIVES: The present study aimed to evaluate the immunohistochemical expression of IL-1ß and Caspase-3 in same OSCC tissue samples with clinicopathological correlation and survival analysis in Indian population. METHODS: A retrospective study was conducted utilizing 40 formalin fixed paraffin embedded histologically diagnosed cases of OSCC comprising of 20 metastatic OSCC and 20 non-metastatic OSCC. RESULTS: Increased expression of IL-1ß and Caspase-3 were observed in metastatic OSCC. Correlation of expression of IL-1ß and Caspase-3 with clinicopathological parameters revealed a significant association between these markers and staging, nodal status and site of the lesion. CONCLUSION: Over expression of IL-1ß and Caspase-3 was associated with advanced stage and poor survival of the patient. IL-1ß overexpression showed significantly lower disease-free survival and disease specific survival as well. Overexpression of IL-1ß and Caspase-3 in incisional OSCC biopsies could be considered for predicting metastasis and survival outcome.