The role of tumor hypoxia in MUC1-positive breast carcinomas

• Published in: Virchows Archiv : an international journal of pathology 2011-10, Vol.459 (4), p.367-375
• Main Authors: Zanetti, Juliana Silva, Soave, Danilo Fiqueredo, Oliveira-Costa, João Paulo, da Silveira, Giórgia Gobbi, Ramalho, Leandra Náira Zambelli, Garcia, Sérgio Britto, Zucoloto, Sérgio, Ribeiro-Silva, Alfredo
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers, Tumor - analysis; Biomarkers, Tumor - metabolism; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Carcinoma, Ductal, Breast - metabolism; Carcinoma, Ductal, Breast - mortality; Carcinoma, Ductal, Breast - pathology; Cell Hypoxia; Disease-Free Survival; Estrogens; Female; Gynecology. Andrology. Obstetrics; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Immunohistochemistry; In Situ Nick-End Labeling; Inactivation; Investigative techniques, diagnostic techniques (general aspects); Kaplan-Meier Estimate; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Mucin-1 - metabolism; Neoplasm Staging; NF-kappa B - metabolism; Original Article; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Prognosis; Proportional Hazards Models; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Retrospective Studies; Tissue Array Analysis; Tumor Suppressor Protein p53 - metabolism; Tumors; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-011-1142-6

Mucin 1 (MUC1) is a glycoprotein that is expressed on apical cell membranes in a variety of normal tissues. MUC1 is involved in cell signaling, inhibition of cell–cell and cell matrix adhesion, apoptosis, proliferation, and transcription. Hypoxia is an important factor that promotes cancer metastasis and stimulates angiogenesis and tumor progression. Hypoxia inducible factor 1 (HIF-1α) and carbonic anhydrase IX (CAIX) are two molecules that are involved in this process. The role of hypoxia in MUC1+ invasive ductal breast carcinomas is not well established. In this study, the expression of MUC1 was correlated with the hypoxia-associated markers HIF-1α and CAIX, as well as several immunohistochemical markers and clinicopathologic features of prognostic significance in 243 invasive ductal carcinomas. MUC1 was overexpressed in 37.0% of patients and correlated with the expression of estrogen receptor ( p  = 0.0001), progesterone receptor ( p  = 0.0001), HIF-1α ( p  = 0.006), VEGF ( p  = 0.024), and p53 ( p  = 0.025). In breast cancer, MUC1 expression has been associated with increased degradation of inhibitor of NF-κB (IκBα), driving NF-κB to the nucleus and blocking apoptosis and promoting cell survival. We analyzed NF-κB expression in MUC1+ breast carcinoma and found a very significant relationship between these proteins ( p  = 0.0001). Our findings indicate that MUC1 may play a role in the regulation of hormone receptors by increasing the inactivation of p53 and targeting NF-κB to the nucleus. Our data also support the notion that activation of HIF-1α in MUC1+ breast carcinomas may modulate VEGF expression, allowing a metabolic adaptation to hypoxia.