Salivary testing, a non-invasive alternative to serum testing, can be an effective modality for diagnosis and prognosis predicting of oral cancer as well as for monitoring the patient's post-therapy status (Nagler et al, 2006). Oral cancer (oral squamous cell carcinoma, OSCC) is the sixth most common human malignancy, with a 5-year mortality rate of approximately 50% (Myers et al, 2000; Kantola et al, 2000), which has not changed significantly in more than 50 years, and a high rate of morbidity (Yuen et al, 1998; Ribeiro et al, 2000; Sparano et al, 2004). The therapeutic modality currently offered to OSCC patients is based on traditional stage-predicting indices (based mostly on the TNM criteria) and on histological grading. Unfortunately, these predictors are subjective and relatively unreliable, as two tumours with identical staging and grading often behave very differently; though one responds to therapy, the other may be lethal. Thus, there has been an ever-growing effort dedicated to the basic research of oral cancer, focusing on the identification of biological indicators for the diagnosis of its biological nature and aggressiveness. However, very few studies have examined tumour markers in the saliva of OSCC patients, though such an examination might be of great benefit because of the direct contact between the oral cancer lesion and saliva. The purpose of this study was to concurrently examine in the saliva of the OSCC (tongue) patients the following eight biomarkers that have been suggested earlier to be related to OSCC (mostly by tissue analysis): carbonyls, 8-oxoguanine DNA glycosylase (OGG1), mammary serine protease inhibitor (Maspin), Ki67, phosphorylated-Src (phospho-Src), Cyclin D1 (CycD1), metalloproteinase-9 (MMP-9) and lactate dehydrogenase (LDH). MMP-9 and LDH have been measured quativavely in saliva of OSCC cancer patients whereas salivary carbonyls were studied by a western gel only. Studies of the other five markers have never been published in the professional literature (Bahar et al, 2007; Shpitzer et al, 2007). Furthermore, all eight markers have never been studied simultanously, nor have they been related to each other or evaluated for their diagnostic sensitivity and specificity values, or for their mutual pathogenetic role in OSCC.

/pdf/salivary-analysis-of-oral-cancer-biomarkers-3oq1dol5iw.pdf

Salivary analysis of oral cancer biomarkers

EBV-associated T and NK-cell lymphoproliferative diseases (EBV-T/NK LPDs) are characterized by the transformation and proliferation of EBV-infected T or NK cells. The 2016 revised World Health Organization classification recognizes the following EBV-positive lymphoproliferative disorders (LPD): chronic active EBV infection (CAEBV) of T- and NK-cell type (cutaneous and systemic forms), systemic EBV-positive T-cell lymphoma of childhood, aggressive NK-cell leukemia, extranodal NK/T-cell lymphoma, nasal type, and the new provisional entity primary EBV-positive nodal T/NK-cell lymphoma. EBV-associated hemophagocytic lymphohistiocytosis (HLH), although not included in the WHO classification because it is a reactive, inflammatory disease, is included in this review because it can be life-threatening and may have overlapping features with other EBV+ T/NK LPDs. EBV+ T/NK LPDs are rare diseases difficult to diagnose and manage properly, because some LPDs have unusual presentations, and discrepancies between clinical and histological findings might be encountered. Furthermore, EBV+ T/NK disorders share some clinico-pathological features, and may evolve into other categories during the clinical course, including malignant transformation of CAEBV. Here, we review the EBV+ T/NK LPDs in terms of their definitions, clinical features, histology, immunophenotype, molecular findings, and pathogenesis. This review aims to increase our understanding and awareness of the differential diagnosis among the different EBV+ T/NK LPDs. New insights into the genetic characteristics of these disorders will also be discussed.

/pdf/epstein-barr-virus-associated-t-and-nk-cell-5dp8uhzvyt.pdf

Epstein-Barr Virus-Associated T and NK-Cell Lymphoproliferative Diseases.

Maspin, a non-inhibitory member of the serine protease inhibitor superfamily, has been characterized as a tumor suppressor gene in multiple cancer types. Among the established anti-tumor effects of Maspin are the inhibition of cancer cell invasion, attachment to extracellular matrices, increased sensitivity to apoptosis, and inhibition of angiogenesis. However, while significant experimental data support the role of Maspin as a tumor suppressor, clinical data regarding the prognostic implications of Maspin expression have led to conflicting results. This highlights the need for a better understanding of the context dependencies of Maspin in normal biology and how these are perturbed in the context of cancer. In this review, we outline the regulation and roles of Maspin in normal and developmental biology while discussing novel evidence and emerging theories related to its functions in cancer. We provide insight into the immense therapeutic potential of Maspin and the challenges related to its successful clinical translation.

Maspin: molecular mechanisms and therapeutic implications

Epstein-Barr virus-associated T- and NK-cell lymphoproliferative diseases: an update and diagnostic approach.

Objectives: To summarize existing evidence about whether the presence of mutant or upregulated p53 is a prognostic factor for patients presenting with squamous cell carcinoma arising from the larynx, oropharynx, hypopharynx, or oral cavity.

Method: Relevant articles were identified using strict criteria for systematic searches. Associations between mutant or upregulated p53 versus wild-type or low/undetectable p53 in relation to overall survival and DFS were summarized by extracting or deriving hazard ratio (HR) estimates. Random-effects meta-analyses were used to account for between-study heterogeneity and to summarize the effect of p53 across studies.

Results: The meta-analyses gave a statistically significant pooled HR for overall survival in oral cavity [pooled HR, 1.48; 95% confidence interval, (95% CI), 1.03-2.11], and for disease-free survival in oral cavity (pooled HR, 1.47; 95% CI, 1.12-1.93) and in oropharynx (pooled HR, 0.45; 95% CI, 0.27-0.73). Despite attempts to limit it, between-study heterogeneity was large in the majority of meta-analyses and the prognostic value of p53 was generally inconsistent and inconclusive across studies.

Conclusion: The meta-analysis results highlight that current evidence about the prognostic value of p53 in patients with squamous cell carcinaoma of the head and neck is inconclusive. Large heterogeneity exists across studies in study-level and patient-level characteristics, making it difficult to ascertain a clear picture. Future studies are required in which p53 expression is investigated in a more standardized and biologically informative manner. In particular, prospectively planned individual patient data meta-analyses are needed to establish the prognostic importance of p53 for specific subgroups of patients undergoing specific treatments. Cancer Epidemiol Biomarkers Prev; 19(2); 574–87

https://cebp.aacrjournals.org/content/cebp/19/2/574.full.pdf

A Systematic Review of p53 as a Prognostic Factor of Survival in Squamous Cell Carcinoma of the Four Main Anatomical Subsites of the Head and Neck

Maspin expression in early oral tongue cancer and its relation to expression of mutant-type p53 and vascular endothelial growth factor (VEGF).

Epstein-Barr virus infected natural killer cell lymphoma in a patient with hypersensitivity to mosquito bite.

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Maspin expression in early oral tongue cancer and its relation to expression of mutant-type p53 and vascular endothelial growth factor (VEGF).

Epstein-Barr virus infected natural killer cell lymphoma in a patient with hypersensitivity to mosquito bite.