Image analysis of the tumor immune microenvironment in recurrent schwannomas
Background: Schwannomas are the most common benign nerve tumors. Unfortunately, there have recurrences in 2-11% cases after total resection. At the moment, little is known about the factors that lead to increased risk of relapse and correlation of biological behavior of tumors with morphological and immunohistochemical patterns. Accurate digital quantification of ICH expression is important to ensure that accurate forecasts are given to patients. It’s known in immuno-oncology that the tumor immune microenvironment affects the prognosis of the disease. We hypothesize that image analysis of H&E and ICH slides of schwannomas may contain prognostic information.
Methods: This was a retrospective review of a digitized H&E-stained whole slide images and IHC slides stained for CD68, CD3, CD8, CD20, MMP2, MMP3. Cases were collected from 121 patients with schwannomas, who was treated in Polenov Neurosurgical Institute in period since 01.01.2005 to 31.12.2022. Tissue specimens from 24 cases (half of them (n=12) had recurrences, others don’t) were all processed and reviewed by a pathologist with using Aperio ImageScope - Pathology Slide Viewing Software (12.4 ver., Leica Aperio AT2) on x400 magnification at the most representative areas that were negative for artifactual distortion. The IHC positive staining cell number percent was counted by using cytoplasmic and membranous modules. IBM SPSS Statistics v.26 (IBM Corporation) program and non-parametric statistical methods were used.
Results: In our study in recurrent schwannomas percent of Antoni A pattern 75% (Q1-Q3: 35-97,5%) was higher than in tumors without relapses 70% (Q1-Q3: 40-80%) in H&E-stained whole slide images, schwannomas percent of Antoni B pattern was 25% (Q1-Q3: 2,5-65%) and 30% (Q1-Q3: 20-60%) in every group respectively. The CD68 positive cell percent in Antoni B pattern was 50% (Q1-Q3: 35-70%) and 60% (Q1-Q3: 40-70%), р=0,266. The CD20 positive cell percent in Antoni A pattern was 1% (Q1-Q3: 1-1%) and 0% (Q1-Q3: 0-1%) in tumors with and without relapses respectively, р=0,045. The CD3 positive cell percent in hot-spots in Antoni A pattern was 5,5% (Q1-Q3: 2,0-7,0%) and 10,0% (Q1-Q3: 5,0-17,5%) in tumors with and without relapses respectively, р=0,045. The CD8 positive cell percent in hot-spots in Antoni A pattern was 53,5% (Q1-Q3: 1-6%) and 4% (Q1-Q3: 2-5%) in tumors with and without relapses respectively, р=0,799. The MMP2 (metalloproteinase 2) percent was 62,5% (Q1-Q3: 37,5%-70,0%) and 35% (Q1-Q3: 22,5-42,5%) in tumors with and without relapses respectively, р=0,039. The MMP3 (metalloproteinase 3) percent was 45,0% (Q1-Q3: 30,0-62,5%) and 15,0% (Q1-Q3: 10,0-42,5%) in tumors with and without relapses respectively, р=0,028.
Conclusions: Schwannomas with recurrences have a higher percentage of Antoni A pattern, higher percentage CD20+ B-lymphocytes and lower levels of CD3+ T-lymphocytes. Also, tumours with adverse clinical prognosis showed higher levels of MMP2, MMP3. Image analysis of the ICH expression of tumor immune microenvironment cells can be used as novel way for identification of schwannomas with increase risk of poor clinical outcomes.
- To find schwannomas with increase risk of poor clinical outcomes by using Image analysis of the tumor immune microenvironment
Dzhamilia Murzaeva, MD
Almazov National Medical Research Centre, Saint Petersburg
Dzhamilia Murzaeva is a PhD student at the Department of Pathology, Polenov Russian Scientific Research Institute of Neurosurgery – branch of Almazov National Medical Research Centre, St. Petersburg. All her educational undertakings were sponsored by the government, up to the level of medical school where he graduated with honors in 2019 in Tyumen. During medical school she worked as a nurse and pharmacist. Dzhamilia’s field of interest is neuropathology, digital pathology, molecular pathology and using of artificial intelligence in tissue imaging. She is passionate to implement in molecular pathology and digital pathology in Siberia. She is involved in daily pathological diagnoses of cases from Federal Neurosurgery Center and Regional Oncological Center. Also she teaches medical students at the university.