# Highlighting the Importance of Signaling Pathways and Immunohistochemistry Features in HCC: A Case Report and Literature Review

## TL;DR

This paper presents a rare case of hepatocellular carcinoma with specific genetic features and discusses its implications for prognosis and treatment.

## Contribution

The paper highlights a rare case of HCC with PIK3CA-positive and PYGO2-negative features, offering insights into its clinical behavior and treatment considerations.

## Key findings

- The case shows elevated alpha-fetoprotein levels and imaging features consistent with aggressive HCC.
- PIK3CA mutation suggests activation of the PI3K/AKT/mTOR pathway, linked to poor prognosis and treatment resistance.
- PYGO2 negativity may indicate different tumor behavior compared to Wnt-positive HCC cases.

## Abstract

Background and Clinical Significance: In hepatocellular carcinoma (HCC), numerous signaling pathways become aberrantly regulated, resulting in sustained cellular proliferation and enhanced metastatic potential. Tumors that lack PYGO2 may not show the same types of tissue remodeling or regenerative features driven by the Wnt/β-catenin pathway, which could make the tumor behave differently from others that are Wnt-positive. PIK3CA-positive tumors are often associated with worse prognosis due to the aggressive nature of the PI3K/AKT pathway activation. This is linked to higher chances of metastasis, recurrence, and resistance to therapies that do not target this pathway. Case presentation: In this paper we present a rare case of hepatocellular carcinoma with PIK3CA-positive and PYGO2-negative signaling pathways, several key aspects of the tumor’s behavior, prognosis, and treatment options. Although alpha-fetoprotein (AFP) levels were significantly elevated, the CT and MRI examination showed characteristics of malignancy, HCC with secondary hepatic lesions and associated perfusion disturbances. The case particularities and immunohistochemistry features are highlighted in the context of literature review, the PIK3CA mutation suggesting the activation of the PI3K/AKT/mTOR pathway, a critical signaling pathway involved in cell survival, proliferation, and metabolism. Conclusions: Due to the aggressive nature of PIK3CA mutations, close monitoring and consideration of immunotherapy and targeted treatments are of crucial importance.