Tez Projesi, Tıpta Uzmanlık
Project no. 22428 · Status: Kapanmış (Yayın bekleniyor) · 2021
Summary
Breast carcinomas constitute one of the most common malignancies all over the world and in our country. Although successful results on survival have been obtained in these malignancies with endocrine therapy for hormone receptors and targeted therapies for Human Epidermal Growth Factor Receptor 2, there is no standardized targeted therapy for tumors with a triple negative phenotype immunohistochemically. This group, which constitutes approximately 20% of all breast carcinomas, progresses with a significantly worse prognosis compared to others. The immunotherapy option, which started with satisfactory results in melanomas, has been tried in many solid tumors and successful results have been obtained. The main purpose of immunotherapy is to restore tumor recognition ability of immune cells whose this ability has been inhibited by different mechanisms. PD-1 (Programmed Cell Death 1) and its ligand PD-L1 (Programmed Cell Death Ligand 1) constitute one of the mechanisms that provide suppression of the immune system. While PD-1 and PD-L1 in healthy tissue prevent damage to the host due to over-activation of the immune system, it has been shown that tumors can escape from the immune system with this mechanism, with their increased levels shown in many malignancies. It is thought that PD-1 and PD-L1 expression in tumors can be determined by evaluating the expression of PD-1 and PD-L1 in tumors to select the patient population that will benefit from treatments for PD-1 and PD-L1 blockade. The term tumor infiltrating lymphocytes represents mononuclear cells in the tumor microenvironment. It has been shown to be a good prognostic marker in the majority of malignancies. Consensus was formed for the determination of tumor infiltrating lymphocyte ratio in breast carcinomas and recommendations were made in this regard. It seems that it will become a necessity to indicate this rate in pathology reports in the near future. Overall 104 cases with immunohistochemically triple negative phenotype were included in our study between 2011 and 2017. In cases where we evaluated PD-L1 and tumor infiltrating lymphocyte ratio, we investigated the effects of these parameters on clinicopathological findings and survival. Our mean follow-up period was 61.5±31.51 months. A positive correlation was found between PD-L1 expression and p53 ratio (p=0.001). The presence of intraepithelial PD-L1 positive staining immune cells in tumors with ?1% PD-L1 expression was noted as a new parameter for PD-L1 evaluation. Although there was no statistically significant difference between tumor infiltrating lymphocytes and clinicopathological findings, a positive correlation was observed between the increase in tumor infiltrating lymphocyte rate and PD-L1 expression (p=0.001). Considering the survival data, we determined that the presence of intraepithelial PD-L1 positive tumor infiltrating immune cells in PD-L1 positive cases increased the overall survival, although the presence of PD-L1 expression did not show a statistically significant difference in this direction (p=0.006). The increase in tumor infiltrating lymphocyte ratio had a positive effect on both overall and distant metastasis-free survival (p=0.040 and p=0.006). Accordingly, it was found that the risk of death was increased 5.18 times (p=0.013) in patients without intraepithelial PD-L1 positive tumor infiltrating immune cells. The risk of death in patients with tumor infiltrating lymphocyte rate ?10% was 5.40 times compared to those with >40% (p=0.024); The risk of distant metastasis was calculated as 11.95 times increased. In our study, it was concluded that the ratio of tumor infiltrating lymphocytes made a statistically significant difference on survival in triple negative breast carcinomas which have a worse prognosis. Although PD-L1 positivity (?1%) prolongs survival, this difference is not statistically significant. The presence of intraepithelial PD-L1 positive tumor-infiltrating immune cells in PD-L1 positive cases prolonged survival in a statistically significant way. We believe that tumor infiltrating lymphocyte ratio should be included in pathology reports as it provides valuable prognostic information. Further studies are needed to elucidate the effect of the presence of intratumoral PD-L1 positive immune cells on prognosis.