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2016 | 14 | 4 | 197–203
Article title

Differential relationship between two hypoxia markers: HIF-1α and GLUT1 and classic prognostic factors in invasive breast carcinoma

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PL
Zróżnicowana zależność pomiędzy dwoma markerami hipoksji: HIF-1α i GLUT1 aklasycznymi czynnikami prognostycznymi w inwazyjnym raku piers
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Abstracts
EN
Background: Tumor hypoxia is an adverse prognostic factor which promotes cancer aggressiveness and limits its radio- and chemosensitivity. The aim of our study was to explore the relationship between endogenous hypoxia markers and classic prognostic factors, including clinical stage and the expression of ER, PR, and HER2 in primary untreated breast carcinoma. Methods: A retrospective immunohistochemical analysis of archived tissue blocks collected from 153 women, who underwent total mastectomy and lymph node dissection, included the expression of two hypoxia-related proteins: HIF-1α and GLUT1. Results: GLUT1 labelling index (LI) showed a positive correlation with T stage (R = 0.18, p = 0.026) and HER2 status (R = 0.25, p = 0.002), and a negative correlation with the expression of ER (R = −0.19, p = 0.017) and PR (R = −0.17, p = 0.032). HIF-1α LI showed a positive correlation with ER expression (R = 0.16, p = 0.045). In the multivariate regression analysis, a different relationship between classic prognostic factors and the two tested hypoxia proteins was proven. Higher GLUT1 expression correlated with ER and PR negativity (p = 0.02 and p = 0.01, respectively) as well as with higher expression of HER2 (p = 0.04). HIF-1α showed no association with PR and HER2, but a positive correlation with ER (p = 0.02). Neither of the hypoxia proteins was associated with a tumor grade. Only one clinical feature, T stage, correlated with both of the hypoxia markers: positively with GLUT1 (p = 0.049) and negatively with HIF-1α (p = 0.01) expression. Conclusions: In breast cancer, GLUT1 expression may be considered an additional prognostic factor which correlates with an adverse status of HER2 and hormonal receptors, and indicates a more hypoxic, radio- and chemotherapy refractory profile of carcinoma.
PL
Tło: Hipoksja w  guzie nowotworowym stanowi niekorzystny czynnik prognostyczny, ogranicza jego promienioi chemiowrażliwość oraz promuje bardziej agresywny przebieg choroby. Przewidywanie rokowania i odpowiedzi na leczenie wymaga wiedzy o związku hipoksji z uznanymi czynnikami prognostycznymi. Celem badania było określenie zależności pomiędzy endogennymi markerami hipoksji w  pierwotnym przewodowym raku piersi a  klasycznymi czynnikami prognostycznymi, takimi jak stopień zaawansowania klinicznego oraz ekspresja receptorów ER, PR i HER2. Metody: Retrospektywna analiza immunohistochemiczna archiwizowanych bloczków tkanek pobranych od 153 kobiet, poddanych mastektomii i limfadenektomii pachowej, objęła ekspresję dwóch związanych z hipoksją białek: HIF-1α i GLUT1. Wyniki: Indeks wiązania GLUT1 (GLUT1 LI) wykazał korelację dodatnią z wielkością guza (R = 0,18, p = 0,026) i ekspresją HER2 (R = 0,25, p = 0,002) oraz ujemną z ekspresją ER (R = −0,19, p = 0,017) i PR (R = −0,17, p = 0,032). HIF-1α LI korelował wyłącznie z ekspresją ER (R = 0,16, p = 0,045). W analizie wieloczynnikowej wykazano zróżnicowaną zależność pomiędzy klasycznymi czynnikami prognostycznymi i testowanymi markerami hipoksji. GLUT1 LI korelował negatywnie z ekspresją ER i PR (odpowiednio p = 0,02 i p = 0,01) oraz pozytywnie z ekspresją HER2 (p = 0,04). Nie udowodniono korelacji pomiędzy HIF-1α LI a ekspresją PR czy HER2, natomiast wykazano jego dodatnią zależność z ekspresją ER (p = 0,02). Żaden marker hipoksji nie korelował ze stopniem zróżnicowania histologicznego nowotworu. Tylko jeden kliniczny czynnik – wielkość guza (T) – korelował z ekspresją badanych białek: dodatnio z GLUT1 (p = 0,049), a ujemnie z HIF-1α (p = 0,01). Wnioski: Ekspresja GLUT1 w raku piersi może stanowić dodatkowy czynnik prognostyczny, korelujący z niekorzystnym statusem receptora HER2 i receptorów hormonalnych oraz wskazywać na bardziej hipoksyczny, oporny na radioi chemioterapię, profil raka.
Discipline
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Year
Volume
14
Issue
4
Pages
197–203
Physical description
Contributors
  • Department of Oncology and Brachytherapy, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Poland; Department of Radiotherapy, Prof. Francis Łukaszczyk Oncology Center, Bydgoszcz, Poland, agnieszka.zyromska@gmail.com
  • Department of Tumor Pathology and Pathomorphology, Prof. Francis Łukaszczyk Oncology Center, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland
author
  • Department of Tumor Pathology and Pathomorphology, Prof. Francis Łukaszczyk Oncology Center, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland
  • Department of Tumor Pathology and Pathomorphology, Prof. Francis Łukaszczyk Oncology Center, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland
  • Department of Oncology and Brachytherapy, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Poland; Department of Radiotherapy, Prof. Francis Łukaszczyk Oncology Center, Bydgoszcz, Poland
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Document Type
article
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YADDA identifier
bwmeta1.element.psjd-3276d5d8-f5c4-4140-bbf0-c11f25a436a1
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