Immunohistochemical Evaluation of Protein P16 Expression in Ovarian Germ Cell Tumors.
2 other identifiers
observational
62
1 country
1
Brief Summary
Ovarian germ cell tumors (OGCTs) constitute 10% of ovarian tumors in Egypt and mainly affect young females. Teratomas are the most common type.Most of teratomas is benign. However, it is liable for malignant transformation. Others are malignant including dysgerminoma, immature teratoma, yolk sac tumor,.etc and accounts 1-1.5% of cancers in young females. The pathogenesis of OGCTs is not clearly understood. P16 is a member of cyclin-dependent kinase (CDK) inhibitors. It arrests the cell cycle in G1 phase, so it is known as a tumor suppressor protein.P16 immunohistochemical(IHC) expression has been widely investigated in different cancers. Its IHC expression is either absent or overexpressed. Overexpression of p16 is documented in Human Papilloma Virus related endocervical neoplasms and High grade squamous intraepithelial lesions of the vulvovaginal region.Absence of p16 expression is detected in multiple cancers such as Lung cancer, colorectal cancer and lymphoma. P16 IHC expression in OGCTs is poorly investigated. One study suggests that absent p16 is involved in proliferation of malignant OGCTs via molecular assessment.Another study suggested that decrease P16 is involved in malignant transformation of Mature cystic teratoma to squamous cell carcinoma.However, Previous studies are still limited and recommended further studies to confirm its results. As the role of altered P16 protein in OGCTs is not widely investigated, we hypothesized that abnormal P16 expression may be involved in its pathogenesis and germ stem cell proliferation.This will give more information about molecular pathways of germ stem cell proliferation to give a hope for CDK inhibitors as novel target therapies in the management of OGCTs.
Trial Health
Trial Health Score
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participants targeted
Target at P25-P50 for all trials
Started Dec 2019
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 24, 2019
CompletedFirst Submitted
Initial submission to the registry
February 23, 2020
CompletedFirst Posted
Study publicly available on registry
February 25, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2021
CompletedResults Posted
Study results publicly available
September 8, 2021
CompletedSeptember 8, 2021
August 1, 2021
1.3 years
February 23, 2020
April 9, 2021
August 12, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
P16 Evaluation in Ovarian Germ Cell Tumors
For P16 IHC staining, the percentage of P16 positive cells and the location of positive signals (nuclear or cytoplasmic) were visually estimated for neoplastic components of all lesions. German Semi-quantitative scoring system were used to evaluate P16 expression as every tumor will be given a score according to the intensity of the cytoplasmic and nucleic staining (no staining = 0, weak staining = 1, moderate staining = 2, strong staining = 3) And the extent of stained cells (0% = 0, 1-10% = 1, 11-50% =2, 51-80% = 3, 81-100% = 4). The final immunoreactive score will be determined by multiplying the intensity scores with the extent of positivity scores of stained cells, with the minimum score of 0 and a maximum score of 12 ( score 0, 1,2,3,4,6,8,9 and 12).
Antibody exposure overnight, assessed up to 3 days for each run of sections assessed.
Measurement of Ki67 Expression in Malignant Ovarian Germ Cell Tumors.
For KI67 IHC staining for malignant cases, percentage of nuclear positivity stained cells were assessed, regardless intensity of staining in all sections examined (at least 1000 tumor cells were counted per section for estimation of KI index).Correlation analysis was used to test the association between Ki-67 and other variables (Spearman' Ranked correlation). A p-value \< 0.05 was considered significant.
Antibody exposure 2 hrs , assessed up to 1 day for each run of sections assessed.
Secondary Outcomes (1)
Correlation Between P16 Cytoplasmic Score and FIGO Staging of MOGCTs.
After obtaining of results and collecting raw data , within 2 months.
Study Arms (3)
Malignant ovarian germ cell tumors ( MOGCTs).
22 cases of malignant ovarian germ cell tumors ; include Dysgerminoma , yolk sac tumor and immature teratomas will be treated by anti P16 antibody and Ki67 antibody.
Mature cystic teratomas.
20 cases of mature teratomas will be treated by anti P16 antibody .
Normally apparent ovaries.
20 cases of normally apparent ovaries will be treated by anti P16 antibody .
Interventions
Treatment of slides that cut from paraffin embedded blocks related to groups by immunohistochemical method by p16INK4a Recombinant Rabbit Monoclonal Antibody (RM267).
Treatment of slides that cut from paraffin embedded blocks related to malignant case group by immunohistochemical method by Ki67 antibody.
Eligibility Criteria
Sixty-two formalin-fixed, paraffin wax-embedded ovarian specimens .These specimens includes: (Group A) 22 malignant ovarian germ cell tumors (MOGCTs): 5 dysgerminomas, 8 immature teratomas (four of them Grade II and the other four are Grade III, FIGO grading system) and 9 yolk sac tumors. The patients ranged in age from 12 to 23 years (median age 16.5 years). The initial diagnosis was re-evaluated according to the WHO Classification of Ovarian Tumors. , (Group B) 20 apparent normal ovarian tissue as a control group that are surgically resected with TAH and salpingo-opherctomy for non-ovarian, non-malignant causes. The patients ranged in age from 42 to 64 years (median 50 years old). and(Group C) 20 mature cystic teratomas as equal benign comparison group.
You may qualify if:
- Ovarian germ cell tumors :
- benign ( mature cystic teratoma ).
- malignant ones ( 5 dysgerminoma , 8 immature teratoma and 9 yolk sac tumor).
- Normal ovaries .
You may not qualify if:
- Epithelial ovarian tumors
- sex cord -stromal ovarian tumors.
- metastatic ovarian lesions.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Assiut University
Asyut, 71111, Egypt
Biospecimen
Formalin fixed paraffin embedded blocks of 62 ovarian specimens will be included in this study. These specimens will be divided into 2 groups: 1-42 surgically resected ovarian germ cell tumors specimens: 22 malignant ones( dysgerminoma , immature teratoma and yolk sac tumor) as a case group and equal 20 benign ones (mature cystic teratoma ) as comparison group . 2- 20 normally apparent ovaries that surgically resected with specimens of total abdominal hysterectomy and salpingo-Oopherctomy for non-ovarian causes in perimenopausal women as a control group .
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Demonstrator at pathology department
- Organization
- Assiut Univercity
Study Officials
- PRINCIPAL INVESTIGATOR
Omar Ahmed, Master
Pathology department- Faculty of medicine - Assiut university
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- observational
- Observational Model
- CASE CONTROL
- Time Perspective
- RETROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Demonstrator at Pathology department - faculty of medicine - Assiut university.
Study Record Dates
First Submitted
February 23, 2020
First Posted
February 25, 2020
Study Start
December 24, 2019
Primary Completion
April 1, 2021
Study Completion
April 1, 2021
Last Updated
September 8, 2021
Results First Posted
September 8, 2021
Record last verified: 2021-08
Data Sharing
- IPD Sharing
- Will not share