Hypoxia-Inducible Factor-1 Alpha Expression Correlates with  Lymphovascular Invasion and Nodal Metastasis in Invasive  Breast Cancer

Agnes Dyah Christinahadi; Berti Julian Nelwan; Muhammad Husni Cangara; Upik Anderiani Miskad; Suryani Tawali; Gunawan Arsyadi

doi:10.31557/apjcb.2026.11.1.103-108

Authors

Agnes Dyah Christinahadi Department of Pathology Anatomy, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
Berti Julian Nelwan Department of Pathology Anatomy, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. Pathology Anatomy Laboratory, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
Muhammad Husni Cangara Department of Pathology Anatomy, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. Pathology Anatomy Laboratory, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
Upik Anderiani Miskad Department of Pathology Anatomy, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. Pathology Anatomy Laboratory, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
Suryani Tawali Department of Public Health and Preventive Medicine, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
Gunawan Arsyadi Department of Pathology Anatomy, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.

DOI:

https://doi.org/10.31557/apjcb.2026.11.1.103-108

Keywords:

breast cancer, hypoxia-inducible factor 1-alpha, metastasis, lymphovascular invasion, lymphatic metastasis, lymph nodes

Abstract

Background: Breast cancer prognosis is critically influenced by lymphovascular invasion (LVI) and lymph node metastasis. Hypoxia-inducible factor-1 alpha (HIF-1α) is a key protein implicated in tumor progression and metastasis. This study aimed to investigate the relationship between HIF-1α expression and the presence of LVI and regional lymph node metastasis in invasive breast cancer.

Methods: This cross-sectional study analyzed 80 paraffin-embedded tissue specimens from participants with stage I–III invasive breast carcinoma. Participants were categorized based on the presence or absence of LVI and lymph node metastasis. HIF-1α expression was evaluated using immunohistochemistry and a semi-quantitative scoring system (IR-Score). The association between HIF-1α expression (positive vs. negative) and clinicopathological variables was analyzed using the Chi-Square test and odds ratio (OR) calculations.

Results: Positive HIF-1α expression was predominant in tumors with LVI (74.1 %) or lymph node metastasis (70.3 %). A significant association was found between HIF-1α expression and LVI (p=0.012), with HIF-1α-positive tumors showing an approximate four-fold increased risk for LVI (OR 3.896; 95 % CI 1.451–10.462) compared to HIF-1α-negative samples. Similarly, a significant association was observed between HIF-1α expression and lymph node metastasis (p=0.031), conferring an increased risk when compared to HIF-1α-negative tumors (OR 3.947; 95 % CI 1.256–12.409). The mean proportion of stained cells was significantly higher in LVI-positive tumors (p=0.015) and metastatic tumors (p=0.039).

Conclusion: HIF-1α expression is significantly associated with lymphovascular invasion and lymph node metastasis in invasive breast cancer. These findings underscore the potential of HIF-1α as a prognostic biomarker for tumors with high metastatic potential.