Abstract

Objective:
Triple-negative breast cancer (TNBC) is an aggressive subtype with limited targeted treatment options. The PIK3CA gene encodes the p110α catalytic subunit of class IA phosphatidylinositol 3-kinase (PI3K), a key regulator of the PI3K/AKT signaling pathway involved in cell growth, survival, and metabolism. Because genetic alterations do not always align with protein-level expression, this study aimed to evaluate immunohistochemical PIK3CA expression in TNBC and to examine its associations with clinicopathological variables and survival outcomes. As an exploratory analysis, PIK3CA mutation status was assessed in a small subset of tumors showing high protein expression.
Methods:
A total of 65 patients diagnosed with TNBC were retrospectively analyzed. PIK3CA expression was assessed using the H-score method and categorized as negative (0–30), intermediate (31–100), and high (101–300). For survival analysis, cases were grouped as negative (0–30) and intermediate–high (31–300). PIK3CA mutation analysis was performed in six cases with high expression. Associations between expression levels and clinicopathological parameters were examined. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan–Meier method and Log-rank test.
Results:
PIK3CA expression was negative in 80.0% (n = 52) of cases, whereas 20.0% (n = 13) showed intermediate–high expression. No significant associations were observed between PIK3CA immunohistochemical expression and clinicopathological features (p> 0.05). PCR-based mutation analysis was performed in the intermediate–high expression subgroup; 33.3% (2/6) of the tested high-expression cases harbored PIK3CA mutations. All deaths occurred in the negative expression group, and overall survival was significantly better in the intermediate–high expression group (p = 0.043); however, no death events were observed in the intermediate–high subgroup (n = 13), and this finding should be interpreted cautiously due to the low number of events. No significant difference in disease-free survival was found between groups (p = 0.588).
Conclusion:
PIK3CA protein expression was not associated with conventional clinicopathological prognostic parameters in TNBC. Nevertheless, moderate–high PIK3CA expression was associated with better overall survival in univariate analysis only, indicating a hypothesis-generating, rather than an independent, prognostic effect. Moreover, despite the lack of significant differences at the immunohistochemical level, PIK3CA mutations were identified by PCR in a limited subset of high-expression cases, highlighting a potential discordance between protein expression and molecular alteration. These findings warrant validation in larger, multicenter studies.”

Key words: Keywords: TNBC; PIK3CA; immunohistochemistry; prognosis; survival.