Tumour Immune and Ki-67 Scoring Methods as Prognostic Biomarkers in Diffuse Large B-cell Lymphoma and Aggressive B-cell Lymphomas

September 3, 2026 updated by: Aliaa Bakr Ahmed, Sohag University

Tumour Immune "Hotness" and Ki-67 Scoring Methods as Prognostic Biomarkers in Diffuse Large B-cell Lymphoma and Aggressive B-cell Lymphomas: An Immunohistochemical Study

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma with heterogeneity in its clinical presentations, biological behaviour and response to therapy (1-4). Nevertheless, despite R-CHOP chemotherapy being successful, a high percentage of patients relapsed early or were primary refractory, highlighting the urgent need for more accurate prognostic biomarkers (2,5).

With the emergence of new discoveries in cancer immunology, the focus has shifted to the tumour microenvironment (TME). The density and presence of tumour-infiltrating lymphocytes (TILs), especially CD3+ T cells and CD8+ cytotoxic T lymphocytes, are key determinants of the anti-tumour immune response (6-8). Now tumours are classified by their immune 'hotness'. 'Hot' tumours, with high T-cell infiltration, are associated with a better prognosis, whereas 'cold' tumours, with immune exclusion or desertion, are associated with a poorer prognosis (9-10).

On the other hand, the Ki-67 proliferation index is still the gold standard marker to measure the growth fraction of neoplastic cells (11). However, the optimal scoring method is yet to be established (12-13). Prognostic information may be obtained by global scoring (i.e. the proliferation index averaged over the whole tumour) and hotspot scoring (i.e. the area of maximum proliferation) (14-15).

In aggressive lymphomas the hotspot index could be a better representation of the highly proliferative clones that drive clinical progression (16-17). The present study was done to assess the combined effect of immune infiltration (CD3/CD8) and proliferation (Ki-67) to build a more accurate prognostic model for patients with DLBCL and other aggressive B-cell lymphomas treated

Study Overview

Status

Not yet recruiting

Conditions

Diffuse Large B-cell Lymphoma and Aggressive B-cell Lymphomas

Study Type

Observational

Enrollment (Estimated)

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

Name: Aliaa Bakr Ahmed, MD
Phone Number: 01062157907
Email: aliaa.bakr@med.sohag.edu.eg

Study Contact Backup

Name: Aliaa Bakr Ahmed, MD
Phone Number: 01062157907
Email: aliaa.bek0@gmail.com

Study Locations

Egypt
- - Sohag, Egypt, 82511
    - Sohag University
    - Contact:
      
      Aliaa Ahmed
      
      Phone Number: 01062157907
      
      Email: aliaa.bek0@gmail.com

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

Child
Adult
Older Adult

Accepts Healthy Volunteers

Sampling Method

Non-Probability Sample

Study Population

Blocks obtained from patients diagnosed as Diffuse Large B-cell Lymphoma and Aggressive B-cell Lymphomas

Description

Inclusion Criteria:

• Patients diagnosed with Diffuse Large B Cell Lymphoma, not otherwise specified (DLBCL, NOS) and other aggressive large B-cell lymphomas, according to current WHO/ICC diagnostic principles.
- Histopathological diagnosis obtained by excisional biopsy, core biopsy or adequate tissue biopsy.
- Availability of FFPE tissue blocks with sufficient viable tumor for immunohistochemical (IHC) staining.
- Diagnostic tissue obtained before the initiation of definitive systemic therapy.
- Available minimum clinical data: age, sex, date of diagnosis, treatment status, and follow-up/survival status.
- For survival analysis: cases with documented follow-up date or date of death/progression.

Exclusion Criteria:

• Inadequate tissue, exhausted block or severe fixation/processing artifact preventing reliable IHC interpretation.
- Extensive necrosis, crush artifact or decalcification artifact in the only available diagnostic tissue.
- Relapse biopsy after chemotherapy without available pretreatment diagnostic tissue.
- Primary Hodgkin lymphoma, indolent B-cell lymphoma without transformation, T-cell lymphoma or metastatic non-lymphoid malignancy.
- Cases lacking essential clinical outcome data for prognostic analysis (except for descriptive staining analysis).
- HIV-associated, post-transplant or primary CNS DLBCL may be excluded or analyzed separately due to distinct biology.

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	Time Frame
Number of Patients with DLBCL/aggressive B-cell lymphomas with assessed by CD3 and Ki67 proliferation index immunohistochemical staining Time Frame: One or two days after staining sections with the markers]	One or two days after staining sections with the markers]

Collaborators and Investigators

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

Sponsor

Sohag University

Investigators

Principal Investigator: Aliaa Bakr Ahmed, MD, Faculty of medicine, Sohag university

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 (Estimated)

October 1, 2026

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

February 1, 2027

Study Registration Dates

First Submitted

August 31, 2026

First Submitted That Met QC Criteria

September 3, 2026

First Posted (Actual)

September 4, 2026

Study Record Updates

Last Update Posted (Actual)