Unusual Infiltrative Patterns of Malignant Cells in Endometrial Carcinoma and Immunohistochemical Expression of P53

March 11, 2023 updated by: Marina Adel Adly, Assiut University

Study of the Unusual Infiltrative Patterns of Malignant Cells and the Immunohistochemical Expression of P53 in Different Histological Types of Endometrial Carcinoma

The goal of this observational study is to clarify the significance of TB, PDC, DR, MELF, and immunohistochemical expression of those infiltrative patterns in patients with endometrial carcinomas (EC). The main questions it aims to answer are:

  1. What is the relationship between TB, PDC, DR, MELF, and other clinicopathological features of patients with endometrial carcinomas (EC)?
  2. What is the association of TB, PDC, DR, and MELF patterns with disease-free survival and overall survival?
  3. Will the evaluation of the immunohistochemical expression of P53 in the TB, PDC, DR, and MELF patterns be important?

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

Endometrial carcinoma is the most common gynecological tumor in economically developing countries. Because of early symptoms, such as abnormal uterine bleeding, endometrial carcinoma is often diagnosed at an early stage with a favorable prognosis. However, 15-20% of these tumors recur after surgery, leading to poor prognosis.

The International Federation of Gynecology and Obstetrics (FIGO) and the TNM classification are the most widely accepted prognostic classifications. They are based on the assessment of the extent of myometrial invasion and lymph node and distant metastasis. Other tumor characteristics such as histological type and grade, tumor size, and lymphovascular space involvement have also been reported as important prognostic factors. According to risk stratification systems, low-grade and early-stage ECs are classified into low or intermediate-low-risk groups. So, it is necessary to find new parameters to identify patients at a higher risk of relapse among early-stage diagnoses in order to treat and follow them properly without overtreating other patients who remain with an excellent prognosis. This is one of the main gaps that need further improvement in the classification and staging of the disease and this issue needs to be addressed in the near future.

Epithelial-to-mesenchymal transition (EMT), the ability of tumor cells to transform epithelial cell traits into mesenchymal cell traits, is associated with the acquisition of tumor infiltration ability in various carcinomas. Recently, the paracrine signaling of tumor cells and stromal cells in the microenvironment at the tumor invasion front has been shown to play an important role in the induction of EMT. In colorectal cancer, the Wnt/β-catenin signaling pathway that induces EMT is activated in single cells and dedifferentiated tumor cells at the tumor invasion front. Hence, single cells and dedifferentiated tumor cells at the tumor invasion front are believed to be the morphological representations of tumor dedifferentiation and migration associated with EMT. Furthermore, cancer-associated fibroblasts (CAFs) have been reported as a microenvironmental factor related to EMT at the tumor invasion front. CAFs are mobilized by tumor cells via growth factors and cytokines and actively interact with tumor cells in addition to forming a myofibroblastic microenvironment that promotes cancer growth at the tumor invasion front. It has been reported that the paracrine signaling repertoire of tumor cells induces EMT in several cancers.

Single cells, dedifferentiated tumor cells, and CAFs are histopathologically reported as tumor budding (TB), poorly differentiated cluster (PDC), and desmoplastic reaction (DR), respectively in colorectal cancer; each of these is a poor prognostic factor. TB has also been reported as a poor prognostic factor in other carcinomas, including those of the stomach, pancreas, and cervix, and DR has been reported in carcinomas of the pancreas, and thyroid. To our knowledge, TB, PDC, and DR are in EC.

In EC, the microcystic, elongated, and fragmented (MELF) pattern of invasion has been reported as an infiltrative morphology at the tumor invasion front. Therefore, the MELF pattern is also a pathological finding that indicates EMT. Moreover, this pattern has a high frequency of lymphovascular space invasion (LVSI) and lymph node metastasis and occurs in extrauterine disease. By contrast, its effect on long-term prognosis has not been reported and its clinical significance is unclear.

P53 is a Tumor suppressor gene at 17p13, 53 kDa. It ensures that cells repair any damaged DNA before cell division by inducing cell cycle arrest to allow time for DNA repair or to force the cell to undergo apoptosis via activation of the BAX gene Overexpression and complete absence are interpreted as mutation-type, with p53 expression levels in between these extremes are taken as wild type. IHC for p53 protein is available in most pathology labs. This will help us to decide the extent of surgery as complete pelvic and paraaortic node dissection may be considered in endometrial cancers with myometrial invasion having p53 mutation, as it could be detected in about 25% of all endometrial cancer patients .p53 expression pattern was associated with tumor budding status in T1 CRC patients as the rate of p53 positivity was higher in budding tumor compared with tumors without budding.

Study Type

Observational

Enrollment (Anticipated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

Endometrial cancer patients

Description

Inclusion Criteria:

  1. Histologically proven Endometrial cancer specimens.
  2. underwent total abdominal hysterectomy, with myometrial invasion.

Exclusion Criteria:

  1. Endometrial biopsies
  2. hysterectomy specimens diagnosed with different pathological lesions rather than EC.
  3. Specimens with prior chemotherapy or radiotherapy.
  4. specimens without myometrial invasion.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Unusual infiltrative patterns and their IHC expression P35
Time Frame: 2 years
Presence or absence of Tumor budding, microcystic elongated fragmented pattern, desmoplastic reaction and poorly differentiated clusters
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

April 1, 2023

Primary Completion (Anticipated)

April 1, 2025

Study Completion (Anticipated)

August 1, 2025

Study Registration Dates

First Submitted

February 23, 2023

First Submitted That Met QC Criteria

February 23, 2023

First Posted (Actual)

March 6, 2023

Study Record Updates

Last Update Posted (Actual)

March 14, 2023

Last Update Submitted That Met QC Criteria

March 11, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • myometrial invasion, P53

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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