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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
Original article / research
Full Version
Histomorphological Features of Ovarian Neoplasms and Expression of p53 and WT1 in Surface Epithelial Tumours: A Cross-sectional Study
Correspondence Address :
Dr. Nupur Kaushik,
15/342B, Gokul Rooms, Opposite Lady Lyal Hospital, Agra, Uttar Pradesh, India.
E-mail: cool.nupurkaushik@rediffmail.com
Introduction: Ovary is the most common site of neoplastic and non neoplastic lesion, can present in childhood to postmenopausal age group and remain the most lethal of all gynaecological malignancies. Tumour Protein (p53) gene mutations or deletions are most common in ovarian carcinoma. However, Wilms’ Tumour gene1 (WT1) and p16 expression are also seen in serous ovarian carcinoma. These Immunohistochemistry (IHC) markers are useful in the differential diagnosis of serous ovarian carcinomas.
Aim: To study histomorphology of ovarian neoplasm along with expression of p53 and WT1 in surface epithelial tumours and to assess the prevalence of various ovarian neoplasms in different age groups.
Materials and Methods: This cross-sectional study was conducted in Department of Pathology, Sarojini Naidu Medical College, Agra, Uttar Pradesh, India, over a period of two years (from September 2018-September 2020). A total of 78 ovarian specimen received in histology laboratory was studied for gross and microscopic features. The p53 and WT1 IHC expression pattern was studied in surface epithelial tumours. Statistical significance was calculated in relation to p53 and WT1 expression with histological type and grade of tumour using Chi-square test.
Results: A total of 78 cases were studied, out of which benign tumours were the most common 40 (51.3%) cases, followed by malignant tumours 32 (41.0%) cases and borderline malignancy 6 (7.7%) cases. The most common benign lesions were mucinous cystadenoma 20 (50%) cases. Serous carcinomas were most common malignant tumours 19 (59.3%) cases followed by Germ Cell Tumours (GCT) 5 (15.6%) cases. All benign and borderline epithelial ovarian tumours were found p53 and WT1 negative. Out of 22 cases of malignant surface epithelial tumour, 14 (63.6%) and 12 (54.4%) were positive for p53 and WT1 respectively and all were serous carcinomas.
Conclusion: Ovarian lesions present with wide spectrum of histomorphological features. The p53 and WT1 show different rates of expression and staining pattern in various epithelial ovarian carcinomas. Hence routine gross, proper histological examination and correct IHC interpretation is required for specific diagnosis.
Benign, Dysgerminoma, Immunohistochemistry, Malignant, Serous carcinomas
Ovarian tumours represent 3% of female malignancies (1). The estimated incidence of developing ovarian cancer in a women lifetime is 1 in 70, which keep increasing with age, and peaks around the eighth decade (2). They are diverse group of tumours with multiple, poorly understood pathogenesis. Understanding genetic mutations, tumour suppressor/oncogenes, and cell regulators provide insight in their pathogenesis and help developing new technologies for early detection (1). Mutations or deletions of p53 gene are the most common molecular alteration in ovarian carcinoma (3). WT1 expression is also associated with variable human cancers and its location in female genital tract which can help in differentiating serous ovarian carcinoma from other tumour. The clinical presentation does not differentiate between benign and malignant tumours. Though the morphology of the ovarian tumours provide a diagnostic clue, but IHC help in differential diagnosis, evaluating molecular changes, which further abet in the characterisation of morphology and clinical behaviour (4). The aim was to study, histomorphology of ovarian neoplasm along with expression of p53 and WT1 in surface epithelial tumours and to assess the prevalence of various ovarian neoplasms in different age groups.
This cross-sectional study was hospital-based, conducted in Department of Pathology, Sarojini Naidu Medical College, Agra, Uttar Pradesh, India, over a period of two years (from September 2018-September 2020). The study was carried out on all gross specimens of clinically diagnosed ovarian neoplasms received in histology laboratory. A total of 78 patients showing ovarian neoplasm on histology were studied. Ethical approval from Institutional Ethics Committee (IEC) was obtained for this study (ethical clearance certificate number of IEC/2021/13). Written consent was taken from all patients and data was used in unidentified manner.
Inclusion criteria: All the ovarian tumour specimens, clinically diagnosed as ovarian neoplasms with definite histopathological diagnosis were considered.
Exclusion criteria: Non neoplastic lesions were excluded. Ovarian tumours treated with neo-adjuvant chemotherapy or radiotherapy was excluded as it could potentially interfere with IHC staining. Inadequate samples were excluded.
Methodology: The histopathological sections from the surgical specimen of ovarian tumours were taken. The samples were fixed in 10% neutral buffered formalin for duration of 12-24 hours. Fixation for long duration greater than 72 hours was avoided. Paraffin wax blocks were made and 3-4 μm sections were taken on poly-L-lysine coated slides. Three sections were taken; one was processed for Haematoxylin and Eosin (H&E) staining while other for p53 and WT1 IHC staining with DAKO FLEX monoclonal mouse antihuman p53 and WT1 antibody. The ovarian tumours were classified according to WHO Classification of Tumours of Female Reproductive organ (2014) (5).
Gross and histomorphological features of all ovarian neoplasms were studied. P53 and WT1 expression and staining pattern of all surface epithelial tumours were studied. Clinical and histomorphological parameters like age, stage of presentation, histological differentiation and grade of tumours were studied in relation to p53 and WT1 expression. All the patients of malignant surface epithelial tumours were followed till the end of study.
Interpretation of staining (6):
1) Nuclear staining for the marker was considered and expressed in percentage.
2) The criteria used to define p53 positive cells are:
a) If >60% of cells are positive, diffuse positive due to missense mutation of p53.
b) If <5% of the cells positive, null positive staining due to nonsense mutation of p53.
3) Cases are considered negative when 5-60% cells show patchy/focal staining due to wild/normal type of p53 mutation.
Nuclear WT1 protein expression was analysed in the cases with >1% positive tumour nuclei was considered positive, and those with zero or <1% was considered negative (4).
Statistical Analysis
The proportion of tumours showing p53 and WT1 positivity is expressed as percentage. Chi-square test was used to find if there is any statistically significant association between p53 and WT1 expression and the parameters studied. Statistical analysis was done using Statistical Package for the Social Sciences (SPSS) version 16.0. The p-value of <0.05 was considered statistically significant.
Among the 78 cases of ovarian neoplasms, the histomorphological diagnosis was made according to the WHO classification (Table/Fig 1) (5). The most common type was surface epithelial tumours in 63 (80.8%) cases, followed by GCT in 07 (8.9%) cases, Sex-Cord Stromal Tumour (SC-ST) in 06 (7.7%) cases and secondary tumours in 02 (2.6%) cases. Metastatic tumours of ovaries were far less common than primary ovarian tumours. Out of 78 cases, 40 (51.3%) cases were benign followed by malignant 32 (41.0%) cases and borderline type 06 (7.7%) cases.
The maximum numbers of cases were found in 31-40 years of age group. The most common age group for benign lesion was 31-40 years with 15 out of 40 (37.5%, cases) and for malignant lesions was 51-60 years with 12 out of 32 (37.5% cases), while borderline type tumours were found in 21-50 years age group. The mean age for benign lesion was 37 years, borderline lesion was 35.5 years and for malignant lesions it was 50.18 years. The lowest age in which the tumour found was 17-year-old girl who presented with pain abdomen and was diagnosed as mucinous cystadenoma. The oldest lady aged 72 years, presented with abdominal pain and distention and diagnosed as high grade serous cystadenocarcinoma (Table/Fig 2).
Out of total 78 cases, the most common benign tumour was mucinous cystadenoma 20 (25.6%) cases, most common malignant tumour was high grade serous-cystadenocarcinoma 15 (19.3%) cases and most common borderline was mucinous cystadenoma borderline type 5 (6.4%) cases. Benign serous tumours were found between 21-50 years of age group. All serous carcinomas cases were found above 40 years of age.
Out of total 78 cases, 7 (8.9%) cases were GCT seen below 30 years of age (Table/Fig 3),(Table/Fig 4),(Table/Fig 5) followed by SC-STs 6 (7.7%) cases of all ovarian tumours seen above 20 years of age (Table/Fig 6),(Table/Fig 7). Metastatic tumours of ovaries were far less common then primary tumours and found in only 2 (2.6%) cases.
Abdominal pain was the most common presenting complaint in all patients. Few patients who complained of abdominal distention along with abdominal pain were diagnosed as having malignant neoplasms subsequently. Only one patient diagnosed with choriocarcinoma presented with abnormal bleeding per vaginum.
Bilateral ovarian tumours were seen in 30 patients. Mostly benign tumours were unilateral; only 9 (22.5%) cases out of 40 benign tumours were bilateral. Maximum numbers of malignant tumour were bilateral in 18 (56.2%) cases out of 32 cases, in which 15 (46.8%) were serous carcinomas. Equal numbers of borderline type cases were unilateral and bilateral respectively. No single case of mucinous cystadenomas was seen bilaterally while all cases were unilateral.
Out of 63 cases of surface epithelial tumours, maximum was benign 35 (55.5%) cases followed by malignant 22 (34.9%) cases. Papillary was the most common growth pattern seen in 40.9% cases. Micropapillary fronds were seen in 03 (75%) cases out of 4 cases of low-grade serous cystadenocarcinoma; however, tubulo-cystic pattern was seen in 02 (100%) cases of clear cell carcinoma. Majority of cases of high-grade serous cystadenocarcinomas showed characteristic histopathological features, represented by destructive infiltration of tumour cells forming branching papillae, slit-like fenestrations and complex glandular architecture. The tumour cells showed mild to moderate to severe nuclear atypia, and frequent mitosis (Table/Fig 8),(Table/Fig 9),(Table/Fig 10).
p53 and WT1 expression in relation to histological type of tumours: Among the total 63 cases of surface epithelial tumours, 22 cases were malignant. Out of 22 epithelial malignant cases 14 (63.6%) and 12 (54.4%) were positive for p53 and WT1, respectively and all were serous carcinomas. All cases of clear cell carcinoma and endometrioid carcinomas were found p53 and WT1 negative. In malignant surface epithelial tumours, statistical association of p53 and WT1 expression with histological type of tumours was found to be insignificant (p-value >0.05). All benign and borderline epithelial tumours were found p53 and WT1 negative (Table/Fig 11),(Table/Fig 12).
p53 and WT1 expression in relation to grade of tumour: Out of 19 serous carcinomas 14 (73.6%) and 12 (63.1%) were positive for p53 and WT1 respectively and all were serous malignancies. Fourteen (93.3%) of high grade serous carcinoma showed diffuse positive staining while one (6.7%) showed aberrant null staining. All low grade serous ovarian carcinomas were negative for p53. Out of 19, 12 serous malignancies were positive for WT1 among which 10 were high grade serous carcinomas and two were low grade serous carcinoma. A 66.7% of high grade serous carcinoma showed positivity for WT1 while 33.3% were negative for WT1, Statistical significance of p53 and WT1 expression with grade of tumour was found insignificant (p-value >0.05) (Table/Fig 13),(Table/Fig 14),(Table/Fig 15),(Table/Fig 16),(Table/Fig 17),(Table/Fig 18).
Association of p53 and WT1 staining with tumour stage and patient survival: Among 22 cases of malignant serous carcinoma, one case of low grade serous cystadenocarcinoma belongs to stage I. One case of high grade serous cystadenocarcinoma belongs to stage II. Twelve cases of serous cystadenocarcinoma (three cases of low grade and nine cases of high grade) and one case each of clear cell carcinoma and endometrioid carcinoma belong to stage III. Five cases of serous cystadenocarcinoma high grade type and one case of clear cell carcinoma belong to stage IV. P53 was negative in stage 1 tumours, all cases of stage 2, 57.1% of stage 3 cases and 83.3% of stage 4 cases were positive for p53. This result was statistically significant by Chi-square test with p-value <0.05. Hence, p53 positivity increased with higher stage. WT1 was positive in all stage 1 and 2 tumours, 50% of the stage 3 and 66.7% of stage 4 cases. This result was statistically significant by chi-square test with p-value of <0.05 but positivity rate of WT1 is low as compared to p53.
All cases of malignant epithelial tumours were followed till the end of study. Among p53 positive tumours, nine (64.3%) cases were alive till the end of study, while five (35.7%) died. Among WT 1 positive tumours, seven (58.3%) cases were alive till the end of the study, while five (41.7%) died. The result was statistically insignificant by chi-square test with p-value >0.05.
Among all gynaecological cancers, ovarian cancer is the second leading cause of mortality (7). Ovarian lesions are difficult to diagnosis, due to absence of symptoms or similar clinical presentation among benign and malignant lesions (8). Histomorphological study of tumour is still today a gold standard method, providing information regarding the frequency and pattern of ovarian tumours (9).
Epithelial ovarian cancers are classified into type I and type II based on molecular and clinico-pathological studies. Type I tumours are characterised by mutations in Kirsten Rat Sarcoma viral oncogene homolog (KRAS), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), Phosphatase and Tensin Homolog deleted on chromosome 10 (PTEN) and Erb-B2 Receptor Tyrosine Kinase (ERBB2), but not TP53, they are genetically stable and typically present at a low stage comprising of low-grade serous, endometrioid, clear-cell, and mucinous ovarian carcinoma. Type II tumours are highly-aggressive, genetically unstable, present in an advanced stage and express a mutated TP53 (10). The IHC results are known to change according to the monoclonal antibody used. The most common antibodies used for p53 are DO-7 and PAb-1801 monoclonal antibodies. These antibodies detect both “wild” type and mutant p53 proteins (11).
The p53 results are influenced by many factors like: a) type of tissue used (p53 antigen is reported to be better expressed in fresh frozen sections); b) different enzymes used for staining; c) Antigen retrieval technique; d) different reported results in the different “cut-off” values; and e) Interobserver variability (12).
In this study, gross and microscopic features of all 78 ovarian neoplasms were studied. Expression of p53 and WT1 was studied in surface epithelial tumours.
In this study, out of total 78 ovarian neoplasms cases, most common lesions were benign 40 (51.4%) cases followed by malignant 32 (41.0%) cases and borderline malignancy 6 (7.7%) cases. The incidence of malignant tumours was higher in present study as compared to Sawant A and Mahajan S; Gupta N et al., Pilli G et al., who found that malignant ovarian tumours constituted 18.2%, 22.9% and 21.6% and of all ovarian tumours, respectively (9),(13),(14).
In this study, out of 78 cases, 63 (80.8%) cases of surface epithelial tumours, 7 (8.9%) cases of GCT and 6 (7.7%) cases of SC-ST which was in concordance with different studies they also found most common surface epithelial tumours followed by GCT and SC-ST (9),(13),(14),(15),(16).
In this study, 63 cases of surface epithelial tumours were studied. Out of which, 35 (55.5%) were benign tumours, 6 (9.9%) were borderline tumours and 22 (34.6%) were malignant tumours, which was found in accordance with other studies (15),(16),(17),(18),(19).
Similar to this study, other studies have also shown that most ovarian tumours occur in reproductive age group. Peak incidence of ovarian tumour was between 21-40 years. Benign ovarian tumours are common in all age group whereas malignant ovarian tumours are more common in elderly like in present study most common group was 51-60 years. Malignant GCT are most common ovarian cancers among children and adolescent females. In patients under age of 21, approximately 60% ovarian tumours were GCT, accounting for two-third of ovarian cancer in first two decades of life (16). In this study, three cases of ovarian tumours were found under the age of 21, out of which 02 (66.7%) were GCT.
According to the literature reports positive results of 48.5% to 69% in studies using the p53 DO-7 antibody (20). In this study, a p53 over-expression was found in 63.6% (14/22) cases, which was found in concordance to Amanullah NAR et al.,Gayathiri G and, Umasamundeeswari R, Choudhary P et al., Psyrri A et al., Kuprjanczyk J et al., Ayadi L et al., Reles A et al., they found p53 expression in 62-83.3% (1),(15),(17),(20),(21),(22),(23). Present study result was non concordance with Mohamed AO et al., Sreeja TT et al., de Graeff P et al., Marks JR et al., they found p53 expression in 35.1-54% cases (10),(19),(24),(25). This may be attributed to heterogeneity of lesions, properties of antibodies used, variability in interpretation of slides, different scoring method applied for p53 immunoreactivity and antigen retrieval technique (17),(19).
According to molecular alterations involved in serous carcinogenesis, the new WHO classification categorises serous carcinoma into low grade and high grade carcinomas. Histopathologically, nuclear pleomorphism, necrosis and mitotic activity help in differentiating between low grade and high grade serous carcinoma. Necrosis is not found in low grade serous carcinoma and the mitotic activity is also low (26). In this study, p53 expression was seen in epithelial ovarian cancer cases, strong positive expression was found in high grade serous cystadenocarcinoma 93.3% (14/15) cases as compared to low grade, all low grade serous carcinomas were negative for p53, which was found in concordance to Amanullah NAR et al., {93.7% (15/16) of high-grade serous cystadenocarcinomas}, Gayathiri G and Umasamundeeswari R {85% (12/14) of high grade and 75%(3/4) of low grade}, Matsuo K et al., {71.4% cases of high grade serous carcinoma}, Nofech-Mozes S et al., {83.6% cases of high grade serous carcinomas} and Koebel M et al., {69% (118/171) cases of high grade serous carcinomas} (1),(15),(27),(28),(29); however, Mohamed AO et al., found p53 expression in 53.7% (29/54) cases of high grade serous carcinomas but none of low grade carcinomas similar to present study (10).
Study of Yemelyanova A et al., reported that p53 immunohistoch-emical scoring systems should not interpret the complete absence of expression as consistent with wild-type TP53. It is implicated that only when both patterns of immunostaining commonly associated with TP53 mutation (60-100% of tumour cells positive and tumours completely negative for p53) were combined, immunohistochemical analysis would give 95% correlation with nucleotide sequencing of the mutations (30).
P53 expression in relation to histological type of tumours: Present study showed expression of p53 in carcinomas mainly, this was reported by others who found that malignant surface epithelial tumours, especially serous cystadenocarcinomas of ovary showed high expression of p53 as compared to the benign and borderline tumour.
Statistically, there was no significant association between p53 expression and histological type of tumours. Review of literature showed conflicting results; some with no significant relation and others with significant relationship. Gursan N et al., found most significant with serous carcinoma (31). In the study of Choudhary P et al., and Ayadi L et al., there was no significant difference in expression of p53 between serous and non serous tumours (17),(22).
In this study, p53 expression was mainly found in high grade serous cystadenocarcinoma. All low grade serous carcinomas were negative for p53. However, the expression of p53 with grade of tumour was statistically non significant which was in concordance with studies conducted by Abubaker J et al., and Herod JJ et al., (32),(33).
High proliferation rate is associated with TP53 alteration, but the association between p53 expression and patient prognosis is controversial (4). Michael A et al., found a significant correlation between the presence of p53 overexpression with stage (p-value <0.01) and poor outcome (p-value =0.05) in patients of ovarian cancer (34); however, Marks JR et al., found no statistical significance between p53 over expression with stage and poor outcome, while they observed that patient with p53 expression had worse median survival (25). Shahin MS et al., found that the p53 wild- type tumours provide the best overall survival when compared with p53 having missense mutation and null mutation (35). In this study, a significant association was found between p53 expression and stage of tumour indicating that increase stage of tumour has high propensity of p53 expression (p-value<0.05), however no statistically significant association was found between patient survival and p53 expression with a p-value of >0.05. Failure of p53 to prognosticate adverse impact on ovarian carcinoma can be explained by the fact that there have been several reports about p53 null mutation which are nearly uniformly non immunoexpressive and sequencing is the gold standard for detection of mutation over immunohistochemistry (35).
WT1 expression in relation to histological type of tumours: WT1 expression is generally used to differentiate serous ovarian carcinomas from other ovarian types in female genital tract (4). Koebel M et al., stated that WT1 expression suggested serous ovarian cancers and approximately 10% of high grade carcinomas can be WT1 negative (36). Sallum LF et al., found 71.4% of low grade serous cystadenocarcinoma and 57.1% of high grade serous cystadenocarcinomas showing WT1 expression (4). In present study, 50% (2/4) of low grade serous cystadenocarcinoma and 66.7% (10/15) of high grade serous cystadenocarcinoma showed positive WT1 expression. A significant association was found between WT1 expression and stage of tumour indicating that increase stage of tumour has high propensity of WT1 expression (p-value <0.05). However the positivity rate of WT1 was low as compared to p53. WT1 expression was low as compared to reports in recent literature, might be due to irregular staining of tissue for WT1. No statistically significant association was found between patient survival and WT1 expression with a p-value >0.05.
The two types of serous ovarian carcinomas harbor different molecular abnormalities. This data from the literature was confirmed from present study by observing the different pattern of expression.
Limitation(s)
The limitation of study was restricted number of samples and use of limited marker.
Benign tumours were more common than primary malignant tumours. Surface epithelial tumours were the most common histological types. Mucinous cystadenoma was the most common primary benign tumour. Serous carcinomas were the most common primary malignant tumour followed by dysgerminoma (GCT). P53 overexpression was seen in high grade serous carcinomas. WT1 can also be used to distinguish serous ovarian carcinomas from another carcinoma. Hence, the use of p53 and WT1 IHC staining is beneficial in the pathologic work-up of ovarian carcinomas.
DOI: 10.7860/JCDR/2022/52010.16153
Date of Submission: Aug 19, 2021
Date of Peer Review: Dec 06, 2021
Date of Acceptance: Jan 09, 2022
Date of Publishing: Apr 01, 2022
AUTHOR DECLARATATION:
• 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
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