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Prognostic value of immunohistochemical markers of intratumoral hypoxia in pregnancy-associated breast cancer.

Carsten F J Bakhuis ,
Paul J van Diest ,
Britt B M Suelmann ,
Natalie D Ter Hoeve ,
Sven van Kempen ,
Pieter J Westenend ,
Sabine C Linn ,
Elsken van der Wall ,
Carmen van Dooijeweert

Abstract

METHODS

Tumour tissues from 148 patients with PrBC and 45 patients with PPBC were used to create a tissue microarray (TMA), and clinical and outcome data were obtained. The TMAs were stained for hypoxia-associated protein markers: glucose transporter-1, carbonic anhydrase IX and hypoxia-inducible factor-1α.

CONCLUSION

This unique study, the first in patients with PrBC and PPBC, showed that, despite their likely exposure to angiogenesis-stimulating factors, intratumoral hypoxia is frequent and affects 79% of patients. Importantly, patients with tumours overexpressing hypoxia markers have significantly worse survival. This suggests that hypoxia may be an important mechanism in carcinogenesis and clinical behaviour of PrBC and PPBC.

RESULTS

Of all 193 tumours, 152 (79%) expressed at least one of these proteins indicative of intratumoral hypoxia. The presence of intratumoral hypoxia was associated with a higher histological grade (83% grade III vs 63%) and frequent hormone receptor negativity (68% vs 39%). In a multivariable analysis, the presence of intratumoral hypoxia indicated a significantly worse prognosis (HR 2.532, 95% CI 1.1 to 5.7) for patients with PrBC and PPBC.

AIMS

Breast cancer (BC) during pregnancy (PrBC) and the postpartum period (PPBC) often exhibits more aggressive tumour characteristics and is associated with a poorer prognosis compared with age-matched nonpregnant patients with BC. The underlying mechanisms for this increased aggressiveness remain unresolved. Intratumoral hypoxia, a known adverse prognostic marker in nonpregnant BC, has not yet been studied in PrBC/PPBC. This is particularly intriguing due to the potential exposure to angiogenesis-stimulating factors during pregnancy, which may influence tumour behaviour.

More about this publication

Journal of clinical pathology

Volume 79
Issue nr. 1
Pages 57-64
Publication date 15-12-2025

Full text links

Publisher website (DOI) 10.1136/jcp-2024-210002
Europe PubMed Central 40451281
Pubmed 40451281

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