Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

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On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



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Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
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Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




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"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2023 | Month : June | Volume : 17 | Issue : 6 | Page : EC15 - EC19 Full Version

Isocitrate Dehydrogenase (IDH1) and p53 Mutations in Gliomas: A Cross-sectional Study from a Tertiary Care Hospital, Karnataka, India


Published: June 1, 2023 | DOI: https://doi.org/10.7860/JCDR/2023/63262.18090
Nissy J Louis, Sapna Patel, Harish Srikantegowda

1. Postgraduate, Department of Pathology, JSSAHER, Mysuru, Karnataka, India. 2. Associate Professor, Department of Pathology, JSSAHER, Mysuru, Karnataka, India. 3. Professor and Head, Department of Surgery, JSSAHER, Mysuru, Karnataka, India.

Correspondence Address :
Sapna Patel,
#3, Vth Main Road, Yadavagiri, Mysuru-570020, Karnataka, India.
E-mail: drsapnaharish@gmail.com

Abstract

Introduction: Gliomas, being the most common Central Nervous System (CNS) neoplasms, are broadly divided into astrocytomas, oligodendrogliomas and ependymomas. World Health Organisation (WHO) 2016 criteria incorporated Immunohistochemistry (IHC), molecular diagnostic techniques and histological tumour grading into its diagnostic criteria. Isocitrate Dehydrogenase (IDH1) mutations are commonly seen in young people with good prognostic implications. The detection of Tumour Protein53 (p53) mutations in gliomas and its association with the grade of the tumour can be used as a diagnostic, prognostic and therapeutic tool for better survival in affected individuals. IHC can be used as surrogate markers in detecting the mutational status of IDH1 and p53.

Aim: To study the expression of IDH1 and p53 mutations in gliomas and to evaluate its association with known clinicopathological variables.

Materials and Methods: This cross-sectional, retrospective, analytical study was conducted in the Department of Pathology at JSSAHER, Mysuru, Karnataka, India, from October 2018 to September 2022. All histopathologically diagnosed glioma cases, who underwent surgery, were appropriately reviewed and graded. IHC was performed for the detection of IDH1 mutational status and p53 expression. The tumour was labelled as, IDH1 positive with cytoplasmic staining and p53 positive when nuclear staining was observed in more than 5% of tumour cells. The p53 expression was further quantified in scores as low ≤8 and high >8 score. The associations of clinicopathological variables and the comparison of the scores of p53 mutation across various categories of gliomas were analysed statistically. The data was analysed using Statistical Package for Social Sciences (SPSS) version 26.0.

Results: The mean age of the study participants was 42.6 years with the standard deviation of 12.8 years. A total of 35 cases (20 males and 15 females) were analysed. The maximum number of cases was in the age group of 31-40 years (n=13) followed by 41-50 years of age group (n=11). Three of them were seen in age less than 20 years. The male: female ratio was 1.33:1. Out of total cases, 20 cases showed IDH1 positivity, 11 cases showed high p53 expression and five cases demonstrated both IDH1 positivity and high expression of p53. A statistically significant association (p-value=0.014) was seen between the grade of the tumour and p53 immunoreaction.

Conclusion: The present study of the detection of IDH1 and p53 mutations, could provide reliable information for improved tailoring of patient therapy as study revealed that, there was a significant association of p53 expression with the grade of the tumour with low expression in low grade gliomas and high p53 expression in high grade gliomas.

Keywords

Astrocytomas, Ependymomas, Oligodendrogliomas, Prognosis, Tumour protein53

Gliomas are the commonest primary intracranial CNS neoplasms. These tumours have features, that are histologically similar to the normal glial cells and are grouped into astrocytomas, oligodendrogliomas and ependymomas, and each of these types has a wide spectrum of aggressiveness (1). The WHO grades 1 and 2 tumours were once referred to as “low grade gliomas,” while the more aggressive and rapidly growing tumours were referred to as “high grade gliomas.” These terminologies are no longer used as per the recommendation given by WHO, because these lesions refer to a heterogeneous group of neoplasms with vastly differing prognosis and treatments due to their diverse biological characteristics (1).

The WHO’s categorisation of gliomas was first released in 1979 and since, 2016 edition of the WHO classification (2), gliomas have been categorised according to histology and molecular characteristics (1). It is envisaged that, this categorisation would result in more biologically homogenous defined diagnostic entities, which will improve patient care, determine therapy response and prognosis more precisely, and increase diagnostic accuracy (2).

The classification of oligodendroglial and astrocytic tumours also changed with the addition of molecular parameters (3). They are classified based on their growth patterns, IDH1 genetic status and ATRX (Alpha-thalassemia/mental retardation, X-linked) immunoreaction (4). Along with those mentioned in the “Consortium to Inform Molecular and Practical Techniques to CNS Tumour Taxonomy- Not Official WHO (cIMPACT-NOW)” updates one through seven, more molecular approaches have been integrated into the 5th (2021) edition (5). IDH1-mutant tumours are associated with a considerably better prognosis than IDH1-wildtype tumours (6). Studies also showed that, “mutant type p53” has a better prognosis and responds well to chemotherapy and radiotherapy when compared to “wild type p53”. Moreover, “p53 positive tumours” are said to have a long survival when compared to “p53 negative tumours” (7) and are also essential in predicting the clinical course of the disease. Assessment of the expression of p53 and IDH1 can be helpful in further stratification of the patients for the specific treatment plan.

The study uses IHC and demonstrates glioma cases into either IDH1 mutant and IDH1 wild-type cases. Additionally, p53 expression and IDH1 mutational status is also associated with various clinical parameters like age of the patient in the present study. IDH mutation and p53 expression are said to have a better prognosis (6),(7) and hence, can be beneficial in monitoring immunotherapy.

The aim of the present study was to study the expression of IDH1 and p53 mutations in gliomas and to evaluate association of IDH1 and p53 expressions with known clinicopathological variables.

Material and Methods

This cross-sectional, retrospective analytical study was conducted in the Department of Pathology at JSSAHER, Mysuru, Karnataka, India. The duration of the study was 48 months (which is four years), from October 2018 to September 2022. A total of 35 glioma cases were included using a convenient sampling technique. Permission to conduct the study was obtained from the Institutional Ethical Committee (JSS/MC/PG/5156/2020-21).

Inclusion criteria: All histopathologically diagnosed cases of gliomas were included in the study.

Exclusion criteria: Patients with no available pathology material for IDH1 and p53 immunostain were excluded from the study.

Study Procedure

All the cases were appropriately evaluated and categorised based on their histological characteristics. Tissues from surgically excised brain tumours were embedded in paraffin and stained with Haematoxylin and Eosin (H&E) after being fixed in 10% neutral buffered formalin. For the retrospective cases (which were from October 2018 to September 2020), the clinical and histopathological data were retrieved from the hospital information system and 3-4 μm thick sections were obtained from representative paraffin blocks and studied. For prospective cases (which were from October 2020 to September 2022), routine processing was done and studied. IHC was performed on 3 μm thick sections that were air-dried and coated with Polylysine. The slides were baked at 60°C for an hour in a hot air oven and then deparaffinised followed by rehydration. The slides were heated in a pressure cooker with antigen retrieval solution and sodium citrate buffer at pH 6. Mouse monoclonal antibrain tumour marker, clone H09 anti-IDH1 R132H/DIA-H09- L Ready To Use (RTU) was used for detection of the presence of IDH1 mutation. Antibody clone H09 reacts specifically with the IDH1R132H point mutation in tissue sections from formalin-fixed brain tumour specimens. The tumour was categorised as IDH1 positive with cytoplasmic staining (8). No scoring or grading systems were used in the present study to further subcategorise the IDH1 positive cases. Sections from brain tumour diagnosed as diffuse astrocytoma was used as positive control and sections treated with phosphate buffer saline, rather than the primary antibody were used as negative control.

Monoclonal antibody p53 (Novacastra, Mouse Monoclonal Antibody: P53-DO7-R-7-CE, RE7290-CE) was used for p53 antigen detection. Diaminobenzidine (DAB) chromogen substrate, which was prepared by mixing 50 μl of DAB chromogen with 1 mL of DAB buffer, was used to detect the bound antibody. If ≥ 5% of the cells in 10 High Power Fields (HPF) showed nuclear staining, the tumour was considered to be p53 positive (9). Based on the percentage of tumour cells, that showed positivity for p53, they were placed into one of the six categories-if the percentage of the total number of tumour cells is less than 5%, then it is scored as zero and when, the percentage of tumour cells is between 5%-30%, 31%-50%, 51%-70%, 71%-90% and greater than 90%, then the score given was 1,2,3,4 and 5, respectively (9). Secondly, the tumour cells were scored based on p53 staining intensity as weak, moderate and intense expression with a score of 1+, 2+ and 3+, respectively (9). The results of p53 IHC were quantified as scores and the weighted score for each tumour was calculated by multiplying the percentage and staining intensity scores, with a score of ≤8 assigned as low 16expression and >8 assigned as high expression (9). Section from colon cancer was used as a positive control, whereas, phosphate buffer saline was applied to sections as a negative control in place of the primary antibody.

Statistical Analysis

The data was analysed using SPSS version 26.0. Descriptive statistics like proportions and inferential statistics like Pearson’s Chi-square test were used as appropriate to evaluate the association of IDH1 and p53 expressions with known clinicopathological variables. Kruskal-Wallis test was used to compare the scores of p53 mutation among various categories of gliomas. The p-value ≤0.05 was considered statistically significant. Graphs were created using Microsoft excel 2019.

Results

The present study included 23 retrospective and 12 prospective cases and comprised 30 cases of astrocytomas (Table/Fig 1)a-d, two cases of oligodendrogliomas (Table/Fig 1)e and three cases of ependymomas (Table/Fig 1)f which were diagnosed histopathologically (histopathological grading for these gliomas has been provided in (Table/Fig 2)). There was a wide age range with gliomas being reported between the age groups of 14 and 67 years the mean age is 42.6 years. The maximum number of cases was in the age group of 31-40 years (n=13) followed by 41-50 years of age group (n=11). Three of them was seen in age less than 20 years. The male: female ratio was 1.33:1 (20 males and 15 females). Majority of the cases belonged to grade 4 {number of cases (n), n=14} gliomas followed by grade 2 (n=12). Among 35 cases of gliomas studied, 20 of them showed IDH1 positivity (Table/Fig 3)a. Pilocytic astrocytomas and ependymomas showed IDH1 negative immunoreaction (Table/Fig 3)b irrespective of the age and the grade of the tumour and oligodendrogliomas showed low expression of p53 (Table/Fig 3)c-f.cases (Table/Fig 2). Less than 5% of the tumour cells (negative p53 expression) were stained for p53 in five cases. The p-value ≤0.05 was considered to be statistically significant and in the current study, there was statistical significance between the expression of p53 and the tumour grade (p=0.014) (Table/Fig 5), but not between the expression of p53 and age (p=0.151) (Table/Fig 4).

Discussion

Gliomas constitute about 80% of all brain malignancies and are further classified into four tumour grades, with grade 1 being the least aggressive and grade 4 being the most aggressive. There are different mutations implicated in the development of gliomas like IDH1, p53, ATRX, Cyclin-dependent Kinase Inhibitor 2B (CDKN2B), and a few other mutations. IDH1 mutation provides a growth advantage to the cells that express it by increasing the level of 2-hydroxyglutarate. The p53 mutation leads to the development of tumours by promoting the uncontrolled growth of cells. The type of therapy is determined by the location, grade of the tumour and the patient’s age (10). Grade 1 and 2 tumours are usually treated with surgery, while grade 3 and 4 tumours are treated with a combination of surgery, radiation, and chemotherapy (10),(11).

The present study showed gliomas with a mean age of 42.6 years. Lewandowska MA et al., and Deng L et al., observed a mean age of 36 years and 42.06 years respectively, in their studies (12),(13). Both, the current study (57.1%) and those conducted by Watanabe T et al., and Chen N et al., found that, males predominated (14),(15). In the present study, for all glioma types, males were predominantly affected except in grade 2 gliomas where, females predominated. The study had the highest percentage of grade 4 gliomas (40%) compared to studies by Mellai M et al., (Table/Fig 6) and Rasmussen BK et al., (12),(13),(14),(16),(17).

The IDH1 mutations are more prevalent than IDH2 mutations among the two frequent IDH mutations in gliomas and occur in both astrocytomas, as well as, in oligodendrogliomas. p53 mutations occur in those cells which are already committed to any one of these lineages (18) and further tells us that, IDH1 mutation occurs early in the development of gliomas which is later accompanied by p53 mutation as the tumour progresses. Hartmann C et al., studied 80 anaplastic astrocytoma cases, among which 40 cases (50%) showed IDH1 immunopositivity (19). The current study showed 75% of grade 3 astrocytomas that demonstrated IDH1 positivity. Capper D et al., in a study showed, 94% of grade 3 oligodendrogliomas positive for IDH1 immunoreaction (20). The present study demonstrated 57% of grade 3 gliomas with IDH1 immunopositivity.

The study conducted by Lewandowska MA et al., analysed that, longer survival was seen in those patients, who had low expression of IDH1 (12). As an example, they have considered two cases of grade 2 astrocytoma, one with low expression (1+ or 2+) of IDH1 and the other with high expression (3+ or 4+) of IDH1, the one with low expression of grade 2 astrocytoma was said to have a longer survival when compared to that of a high expression (12). Previously, IDH mutation was considered to be the single most prognostic marker in Glioblastoma Multiforme (GBM) (21),(22). Hence, IDH mutations in gliomas are targeted for diagnostic, therapeutic, and prognostic purposes (23). Mellai M et al., suggested that, IDH1 was said to have a prognostic significance in grade 3 and grade 4 gliomas and had better survival, when compared to those patients, who had gliomas without IDH1 mutations (16). However, Balss J et al., found that, there was no association between IDH1 and p53 mutation (18). The present study also demonstrated a similar observation.

p53: In approximately, 50% of all malignancies, the p53 gene is mutated and greater than 65% of gliomas have the p53 protein genetically altered. In 2006, Hu X et al., studied 152 glioma patients (24). The mean age in that study, was 40.3 years ranging from 21-79 years, had male predominance and p53 expression was seen maximum in grade 3 glioma, which was similar to the present study. The current research, however, demonstrated a significant association (p-value=0.014) between p53 expression and the tumour grade, which was consistent with the 81 case study by Cho MY et al., (25). The latter study also said that, the frequency of p53 expression was the highest in grade 3 astrocytoma when compared to grade 4. The maximum expression in the present study was seen in grade 3 (which is 100%), followed by grade 4 and then grade 2. Low expression of p53 was seen maximum in grade 2 tumours followed by grade 3 and then grade 4. But, the frequency of gliomas expressing high immunopositivity of p53 was seen highest in grade 4. This result suggested that, p53 targeted therapy could be helpful in these patients if detected in the early stages of disease progression.

Popova SN et al., studied gliomas in 219 cases over a period of 18 years and analysed that, none of the oligodendroglioma cases showed high expression of p53, which was consistent with the present study (26). A descriptive study done by Arshad H et al., grouped the gliomas into four grades and performed p53 and MIB1 immunohistochemical stains (27). They concluded that, the histopathological grade was the most important prognostic factor in regard to the survival of the patient and the IHC staining could be clubbed along with the histological grade, as an additional tool in knowing the clinical course of the patient (27). Another study, conducted at the University of Texas from the tissue samples obtained from 182 patients determined the significance of p53 as a prognostic marker and suggested that, the IHC status of p53 could be an important predictor for patient survival (7).

Limitation(s)

The sample size of the present study was low therefore, more studies using a large number of cases are required to obtain more corroboration. An equal distribution of cases was not obtained among all the tumour grades of gliomas and follow-up of the cases was not possible. Hence, addressing the parameters like the recurrence of the tumour, prognosis and survival studies of the patients was not done. Selection bias cannot be ruled out, as it was a single Institutional study. Ancillary techniques like Fluorescent In-situ Hybridisation (FISH) and molecular detection techniques could not be performed in the present study, considering its unavailability in the Institute where the study was conducted.

Conclusion

The hybrid taxonomy of WHO CNS 2021 criteria, include the reporting of gliomas in structured layering and integrated diagnoses using histopathological examination, immunohistochemical assessment and molecular studies in certain entities. The present study revealed that, there was a significant association of p53 expression with the grade of the tumour with low expression in low grade gliomas and high p53 expression in high grade gliomas. Therefore, the present study emphasises the detection of IDH1 and p53 mutations in gliomas, that may act as an objective tool to supplement subjective methods of evaluation in differentiating low grade gliomas from high grade gliomas.

Acknowledgement

The authors would like to thank the technical staff of the hospital for their skillful assistance in the present study. The authors are also thankful to the Head of the Department for the valuable support throughout the study and also, wish to thank Dr. Suchitha S for her valuable contribution and expertise in all aspects of the present study.

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DOI and Others

DOI: 10.7860/JCDR/2023/63262.18090

Date of Submission: Feb 04, 2023
Date of Peer Review: Mar 03, 2023
Date of Acceptance: May 25, 2023
Date of Publishing: Jun 01, 2023

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Feb 03, 2023
• Manual Googling: Apr 18, 2023
• iThenticate Software: May 24, 2023 (6%)

ETYMOLOGY: Author Origin

EMENDATIONS: 6

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