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Volume 2
Journal of Molecular Cancer
Cancer & Primary Healthcare 2019
May 20-21, 2019
Cancer Research & Oncology
Primary Healthcare and Medicare Summit
May 20-21, 2019 | Rome, Italy
25
th
Global Meet on
World Congress on
&
The Immunogradient of CD8+ cell density in the tumour-stroma interface zone predicts
overall survival of patients with hormone receptor-positive invasive ductal breast
carcinoma
Dovile Zilenaite
Vilnius University Hospital Santaros Clinics, Lithuania
Statement of the Problem:
Tumour infiltrating lymphocytes (TIL) are associated with better prognosis in
triple-negative and HER2-positive breast cancer (1, 2), and TIL assessment by digital image analysis (DIA)
has been successfully implemented in colorectal and other cancers (3). However, results in hormone receptor-
positive breast cancer (HRBC) based on manual scoring remain contradictory (2). Here we used an automated
DIA method to extract prognostic value of novel Immunogradient indicators in CD8+ cell density profiles in
HRBC.
Methodology & Theoretical Orientation:
Surgically excised HRBC samples from 102 patients were
immunohistochemically stained for CD8, digitized and analysed by the HALO™ platform. The DIA data was
subsampled by a hexagonal grid and explicit rules were then used to extract the tumour-stroma interface zone
(IZ) and compute novel Immunogradient indicators from TIL density profiles across the IZ. The prognostic
value was evaluated by survival analysis. Findings: The IZ Immunogradient indicators (mean CD8+ density
in the tumour aspect of the IZ, Immunodrop, Centre of Mass) allowed prognostic stratification of patients in
univariate analyses (hazard ratios: 0.21 (p=0.0002), 2.79 (p=0.0140), and 0.28 (p=0.0044), respectively). The
best and independent indicator of better OS by multiple Cox regression model (hazard ratio: 0.23 (p=0.0007))
was an aggregated Immunogradient factor (Agg. Factor), obtained by the sum of two factor scores (CD8+
density and “gradient towards the tumour”). Remarkably, the aggregated Immunogradient factor revealed a
striking drop of patients’ survival probability 5 years after surgery.
Conclusion & Significance:
The Immunogradient indicator for CD8+ cell density is an independent predictor
of better OS in HRBC patients with the particular diversion of OS 5 years after the surgery.
Biography
Dovile Zilenaite is a medical geneticist at the National Center of Pathology, Affiliate of VULSK and a doctoral student at Vilnius University
Faculty of Medicine. Her research focuses on the development and standardization of multiple IHC procedures for multiparametric and
spatial analysis, digital image analysis and prognostic modelling in the breast cancer patients. Main scientific interests: genetics, cancer
biology, immunology, digital analysis and analytics of whole slide pathology images to describe heterogeneity of tumor cell population
and microenvironment.
zildov@vpc.ltJ Mol Cancer, Volume 2