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Relationship: 2829

Title

A descriptive phrase which clearly defines the two KEs being considered and the sequential relationship between them (i.e., which is upstream, and which is downstream). More help

Promotion, ovarian adenomas leads to Promotion, Ovarian Cancer

Upstream event

The causing Key Event (KE) in a Key Event Relationship (KER). More help

Promotion, ovarian adenomas

Downstream event

The responding Key Event (KE) in a Key Event Relationship (KER). More help

Promotion, Ovarian Cancer

Key Event Relationship Overview

The utility of AOPs for regulatory application is defined, to a large extent, by the confidence and precision with which they facilitate extrapolation of data measured at low levels of biological organisation to predicted outcomes at higher levels of organisation and the extent to which they can link biological effect measurements to their specific causes.Within the AOP framework, the predictive relationships that facilitate extrapolation are represented by the KERs. Consequently, the overall WoE for an AOP is a reflection in part, of the level of confidence in the underlying series of KERs it encompasses. Therefore, describing the KERs in an AOP involves assembling and organising the types of information and evidence that defines the scientific basis for inferring the probable change in, or state of, a downstream KE from the known or measured state of an upstream KE. More help

AOPs Referencing Relationship

AOP Name	Adjacency	Weight of Evidence	Quantitative Understanding	Point of Contact	Author Status	OECD Status
Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia	non-adjacent	Moderate	Low	Cataia Ives (send email)	Under development: Not open for comment. Do not cite	Under Development

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KER.In general, this will be dictated by the more restrictive of the two KEs being linked together by the KER. More help

Term	Scientific Term	Evidence	Link
human	Homo sapiens	High	NCBI
mice	Mus sp.	High	NCBI

Sex Applicability

An indication of the the relevant sex for this KER. More help

Sex	Evidence
Female	High

Life Stage Applicability

An indication of the the relevant life stage(s) for this KER. More help

Term	Evidence
Adult	High

Key Event Relationship Description

Provides a concise overview of the information given below as well as addressing details that aren’t inherent in the description of the KEs themselves. More help

Ovarian tumors are abnormal mass of tissues grows on or in the ovaries of the aged females. Ovarian adenomas / cystadenomas are very common and benign type of tumors, which are found in epithelial tissues of the ovaries. Almost 60% of the ovarian tumors are due to the epithelial neoplasm (abnormal growth of tissue) of the ovary (Limaiem et al. 2022). Ovarian adenomas are classified into different categories such as serous cystadenoma, mucinous cystadenoma, endometrioid cystadenoma, clear cell cystadenoma and seromucinous systadenoma. Reports have shown that ovarian serous cystadenoma can turn progress to serous carcinoma (Cheng et al. 2004). Frequent mutations of two genes (BRAF and KRAS) are identified as the cause of the serous carcinoma.

Evidence Collection Strategy

Include a description of the approach for identification and assembly of the evidence base for the KER. For evidence identification, include, for example, a description of the sources and dates of information consulted including expert knowledge, databases searched and associated search terms/strings. Include also a description of study screening criteria and methodology, study quality assessment considerations, the data extraction strategy and links to any repositories/databases of relevant references.Tabular summaries and links to relevant supporting documentation are encouraged, wherever possible. More help

Morphological features of the different ovarian adenomas in the epithelium tissue of adult female ovaries are distinct from the each other. Endometrial hyperplasia in the ovaries of the aged female frequently observed as a consequence of the high level of the estrogen activity in the stroma cells.

MacDonald et al., had shown androstenedione production rate and estrogen level in the postmenopausal woman are five-fold higher than the normally expected level. Increased androstenedione production rate leads towards the formation of mucinous cystadenocarcinoma in the stromal cells of the ovary (MacDonald et al. 1976). Pascal et al., had reported ovarian mucinous cystadenoma with distinct feature of luteinization of the stroma cells in a 32 year old female patient (Pascal and Grecco 1988). Epithelial neoplasma of the ovary classified as borderline ovarian tumors (BOT), which have separate distinguishing features than the carcinoma. Ovarian cystadenomas are benign neoplasms present in the epithelial tissues of the patients are also categorised as borderline ovarian tumors.

Evidence Map 2.0

ID	Experimental Design	Species	Upstream Observation	Downstream Observation	Citation (first author, year)	Notes

Evidence Map

Addresses the scientific evidence supporting KERs in an AOP setting the stage for overall assessment of the AOP. More help

Title	First Author	Biological Plausibility	Dose Concordance	Temporal Concordance	Incidence Concordance

Biological Plausibility

Dose Concordance Evidence

Temporal Concordance Evidence

Incidence Concordance Evidence

Uncertainties and Inconsistencies

Addresses inconsistencies or uncertainties in the relationship including the identification of experimental details that may explain apparent deviations from the expected patterns of concordance. More help

Balat et al., had reported the detection of unthreatened late pregnancy with a large mucinous cyst adenoma of the ovary in a female patient (Balat et al. 2002). Vidhale et al., had reported the detection of serous cystadenoma in the ovary, which is benign in nature (Vidhale et al. 2022). Mittal, et al., had reported the detection of benign type of mucinous cystadenoma in the ovary (Mittal et al. 2008).

Known modulating factors

This table captures specific information on the MF, its properties, how it affects the KER and respective references.1.) What is the modulating factor? Name the factor for which solid evidence exists that it influences this KER. Examples: age, sex, genotype, diet 2.) Details of this modulating factor. Specify which features of this MF are relevant for this KER. Examples: a specific age range or a specific biological age (defined by...); a specific gene mutation or variant, a specific nutrient (deficit or surplus); a sex-specific homone; a certain threshold value (e.g. serum levels of a chemical above...) 3.) Description of how this modulating factor affects this KER. Describe the provable modification of the KER (also quantitatively, if known). Examples: increase or decrease of the magnitude of effect (by a factor of...); change of the time-course of the effect (onset delay by...); alteration of the probability of the effect; increase or decrease of the sensitivity of the downstream effect (by a factor of...) 4.) Provision of supporting scientific evidence for an effect of this MF on this KER. Give a list of references. More help

Modulating Factor (MF)	MF Specification	Effect(s) on the KER	Reference(s)
Not know

Quantitative Understanding of the Linkage

Captures information that helps to define how much change in the upstream KE, and/or for how long, is needed to elicit a detectable and defined change in the downstream KE. More help

Not enough data is available

Response-response Relationship

Provides sources of data that define the response-response relationships between the KEs. More help

Horn et al., had evaluated the 74 cases of borderline ovarian tumors and shown that majority of the cases are belongs to the serous borderline ovarian tumors (60.8%), followed by the mucinous borderline ovarian tumors (25.7%). Adenoma in the borderline ovarian tumors was found in 86.5% cases. The report had suggested that the association of papillary tubal hyperplasia and salpingoliths with the borderline ovarian tumors (Horn et al. 2017).

Time-scale

Information regarding the approximate time-scale of the changes in KEdownstream relative to changes in KEupstream (i.e., do effects on KEdownstream lag those on KEupstream by seconds, minutes, hours, or days?). More help

Observed in months to years

Known Feedforward/Feedback loops influencing this KER

Define whether there are known positive or negative feedback mechanisms involved and what is understood about their time-course and homeostatic limits. More help

Not known

Domain of Applicability

A free-text section of the KER description that the developers can use to explain their rationale for the taxonomic, life stage, or sex applicability structured terms. More help

Observed in adult female (human) also in rodents.