Brief Commentary

Advances in molecular oncology technology and their application to personalized cancer care have evolved very rapidly over the past 5 years. At the same time, there are a lot of conflicting and often misleading statements available on the world wide web. This results in confusion and misunderstanding among cancer patients and their well-wishers. We realized that there was an urgent need for developing a consensus document to address this unmet need. Oncology Gold Standard and Molecular Oncology Society, therefore, took up the challenge and formed an expert group that together prepared this consensus statement on counseling patients for molecular testing and personalized cancer care. This is intended to benefit patients, family and friends by improving their broad understanding and equip them to make an informed decision and take active participation in decision-making for their own cancer management - with respect to prevention, diagnosis, treatment, and follow-up of cancer.

Biopsies have been the best tool in the hands of the clinicians for the appropriate management of malignancies including diagnosis, prognosis and reassessment. They are and have been the gold standard in their diagnosis. Due to certain unavoidable limitations of needle biopsy, there is emergence of a new biomarker in oncology called LIQUID BIOPSY: Analysis of circulating tumour cells (CTC) and circulating free tumor DNA (ctDNA) from the peripheral blood. As this technology evolves it may prove to be a critical component of personalized medicine in this modern era of diagnostics. Liquid biopsy has a great potential in cancer diagnosis, monitoring and predicting survival. Nevertheless false positive results exist. The major challenge with this technology is assay sensitivity and specificity. This mini-review tries to fill the gap between reality and our hope of this “liquid biopsy”.

Pediatric tumors are challenging in the context of best diagnosis, treatment, and prognosis. For tumors which have a genetic association or a cancer predisposition syndrome, the prognosis depends on accurate diagnosis. The application of molecular genetics to pediatric tumors has resulted in better diagnostic and prognostic factors for patient management. Molecular diagnostic techniques, such as reverse transcription polymerase chain reaction and fluorescence in situ hybridization (FISH), have become important tests for childhood tumors. Targeted therapies are aimed at specific translocations which are detected by FISH. Molecular techniques help in monitoring of minimal residual disease in childhood tumors.

The current trends of artificial intelligence (AI) and machine learning, specifically the amazing success achieved by artificial refurbished neural network architecture deep learning (DL), algorithms used like in alpha go, could greatly benefit cancer detection, personalized cancer treatment, and cancer drug discovery. New models like DL have recently arrived and are offering a leap step into classifying cancer types and even potential drug discoveries. These targeted AI will continue emerging and will build up toward the final fight of cancer: When AI, with the help of advance sensors that will provide data, can diagnosis cancer in stage zero.

Thyroid cancer is the most common of all endocrine tumors. In most countries, a steady increase in the incidence of thyroid cancer (mainly papillary carcinomas) was observed in both sexes, whereas mortality has declined. Thyroid nodule is the most common presentation of thyroid cancer and according to Bethesda reporting system is categorized into six different disease categories based on histopathological pattern. The indeterminate categories require further investigation which is generally in the form of a surgical or invasive procedure for confirmation of nature of disease. Our article is describing the various molecular markers that are linked with different subtypes of thyroid cancer and their usage in guiding diagnosis, investigative approach and prognostication in thyroid cancer especially the indeterminate categories. We discuss the various tests available for us currently for detecting the genetic alterations and thus help us frame further approach algorithms for detection of thyroid cancers.

Introduction: Lung cancer accounts for the highest mortality globally, and there is a need to find new strategies and novel treatment options. Lung cancer is genetically heterogeneous across various ethnic populations, and therefore identifying the mutational landscape in Indian patients is important. Methods: The aim of the pilot study is to identify the prevalence and temporal sequence of molecular lesions in lung cancer patients from a regional cancer institute in South India using the circulating tumor DNA technique. Genotyping was performed on 26 newly diagnosed metastatic lung cancer patients using Illumina Omni Express Exome. Chip data were inspected using Genome Studio and subsequently exported for use with PLINK and further annotation was performed. Results: Seven genes including TP53 (61.5%), MUC16 (57.6%), KRAS (38.4%), STK11 (19.2%), Epidermal growth factor receptor (15.3%), ataxia telangiectasia mutated (15.3%), and nuclear factor-?ß (7.6%) demonstrated high incidence of mutations in patients. The other genes identified were observed in <5% of patients. Several types of mutations including missense, silent, nonsense, and frameshift mutations were observed in these genes. Conclusion: Integration of mutational profiling to identify gene mutations is required to facilitate personalized lung cancer therapy.

Introduction: Sinonasal and nasopharyngeal tract masses can be difficult to diagnose as they have unusual diverse morphology and histopathology with anatomic and embryonic distinction and immunohistochemistry (ICH) becomes mandatory for diagnosis. Aims and Objectives: A retrospective observational study of 5 years from 2011 to 2016 till date was conducted at a tertiary care center. Total analyses of 200 cases were done to study the clinical presentation and histomorphology of all sinonasal and nasopharyngeal masses with gender and age distribution and highlightling the entities with rare clinicopathological and histological presentation and study of ICH in these lesions. Results: Out of total 200 cases, 148 (74%) were inflammatory or infective non-tumorous masses and 52 (26%) were neoplastic, out of which 27 (13.5%) were benign and 25 (12.5%), were proven to be of malignant etiology. In benign neoplastic category, unusual entities were juvenile angiofibroma, meningioma, and hemangioma. Among the cases with atypical clinicopathological presentation and unusual entities which required ICH for diagnosis were chordoma, diffuse large B-cell lymphoma, esthesioneuroblastoma, sinonasal adenocarcinoma, adenoid cystic carcinoma, and nasopharyngeal carcinomas. Conclusion: Sinonasal and nasopharyngeal masses are having diverse clinical presentations at different sites having unusual clinical presentation and varied histopathology and the unusual varieties also occur which rare to these locations and should be promptly diagnosed with ICH for early, accurate and optimal treatment.

Background: Epstein–Barr virus is a human herpes virus ubiquitously infecting 90% of world population and causing 1% of tumors worldwide. The objectives were to establish etiopathogenesis in the Epstein-Barr virus (EBV) associated malignancies reported in our laboratory using the gold standard test, i.e., chromogenic in situ hybridization (CISH) for Epstein-Barr virus - encoded RNA (EBER). Aims and Objectives: We performed CISH on 244 cases of associated malignancies in the year 2013–2016, the decision was taken after H and E diagnosis and immunohistochemistry confirmation. Observation and Results: In the period of 2013–2016, 253 cases were evaluated by CISH for EBER. The age range in our study was 5–88 years with the mean age of 41.8 years, a slight male predominance was noted with male: female ratio of 1.5:1. CISH in 61 Classical Hodgkin lymphoma cases of 90cases were positive Conclusion: EBER ISH is the single best histochemical assay for defining EBV - related neoplasia. It is likely that emerging technologies such as gene expression profiling and proteomics will identify patterns of viral and human gene expression correlating with diagnosis, prognosis, and outcome in response to therapy.

Editorial

Background: Latest advances indicate that RUNX3 is a candidate tumor suppressor in several types of human cancers, including renal cell cancer. However, its definitive role is not yet established. Vascular endothelial growth factor (VEGF) has been widely studied as a surrogate marker of angiogenic activity and prognostic marker in renal cancer for monitoring treatment response and detection of early relapse. The aim of the study was to examine the clinical significance of RUNX3 expression and serum VEFG in series of renal cancer patients using quantitative real-time polymerase chain reaction and standard enzyme-linked immunosorbent assay kit and find its correlation with renal cancer stage, grade, and histopathology. Materials and Methods: We reviewed our prospectively collected renal cancer database of 47 patients. All patients were evaluated preoperatively and staged and underwent partial or radical nephrectomy as per the feasibility criteria. RUNX 3 expression in tumor tissue and adjoining parenchyma was sampled in all patients, and serum levels of VEGF were measured in pre-and post-operative period on day 7 and day 30 after surgery. 10 age- and sex-matched healthy volunteers served as control group. Results: We observed that RUNX3 gene expression was significantly lower in tumor tissue than in normal renal parenchyma of a renal cancer patient. The serum VEGF levels were significantly increased in patients with renal cell carcinoma (RCC) compared to normal healthy volunteers and showed decreasing trend after the surgery. Loss of RUNX3 gene expression and higher VEGF levels strongly correlated with high-grade tumors; however, it was not related to tumor size and histopathology. There was no correlation of RUNX 3 with VEGF levels in RCC patients. Conclusion: The results of this study showed that renal cancer patients had increased VEGF levels which were effectively alleviated by curative resection. Lower expression of RUNX3 in renal cancer suggests its tumor suppressive role and new insights into targeted therapies linking RUNX3 gene may have some diagnostic and therapeutic implications in RCC patients. We did not find any correlation between RUNX3 gene and serum VEGF