Assessment of PI3KCA immunohistochemical expression and tumor infiltrating lymphocytes (CD4 and CD8) in invasive breast carcinoma and their relation to molecular subtypes

Document Type : Original Article


1 Pathology Department, Faculty of Medicine, Tanta University, Egypt.

2 Pathology department, Faculty of medicine, Tanta university , Tanta, Egypt.

3 Pathology Department, Faculty of Medicine, Tanta University, Tanta, Egypt.


Background: Invasive breast carcinoma (IBC) exhibits multiple genetic and epigenetic alterations. Phosphatidylinositol-4, 5-biphospate- 3 -kinase, catalytic subunit alpha (PI3KCA) is frequently mutated in IBC and plays a key role in cell survival and growth. However, the role of PI3KCA protein expression in IBC and its subtypes is still controversial.  Tumor infiltrating lymphocytes (TILs), including CD4+ and CD8+ T cells are important biomarkers in breast carcinoma and regulate tumor microenvironment. TILs expression levels, either high or low, are contradictory regarding IBC patients’ survival and prediction of chemotherapy response. Aims: This retrospective study aimed to assess the immunohistochemical expression of PI3KCA, CD4, and CD8 in IBC patients. Materials and Methods: Paraffinized tissues were prepared from IBC patients (n=63) collected from Pathology Department, Faculty of Medicine, Tanta University.  We assessed the expression of PI3KCA, CD4, and CD8 in relation to the available clinicopathological parameters and molecular subtypes of IBC. Moreover, we correlated immunohistochemical expression of PI3KCA to CD4/CD8 ratio in IBC cases. Results: Positive PI3KCA immunohistochemical expression, low positive CD4 and high positive CD8 T-lymphocytes were detected in 54%, 50.8%, and 49.2% of the studied cases, respectively, with statistically significant relations with higher tumor grade, advanced tumor stage, triple negative breast cancer (TNBC), lymphovascular and perineural invasion, and presence of major in-situ component. There was a significant strong negative correlation between PI3KCA expression and CD4/CD8 ratio. Conclusions: Positive expression of PI3KCA, low CD4+, high CD8+ T cells as well as low CD4/CD8 ratio in IBC correlate with unfavorable clinicopathological parameters. This study helps to evaluate the combined novel targeted therapy with immunomodulatory agents.


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