Hypoxia-Inducible Factor 1α and AT-Rich Interactive Domain-Containing Protein 1A Expression in Pituitary Adenomas: Association with Pathological, Clinical, and Radiological Features.
BACKGROUND
Hypoxia-inducible factor (HIF) plays a major role in tumorigenesis and cancer progression. In hypoxic conditions, HIF is upregulated and has been shown to activate multiple genes required for cells to adapt to hypoxia. AT-rich interactive domain-containing protein 1A (ARID1A), a SWI/SNF (switch/sucrose nonfermentable) chromatin remodeling gene has context-dependent tumor-suppressive and oncogenic roles in cancer. We assessed the correlations between the expression and mutations of HIF1A and ARID1A in histopathologically confirmed pituitary adenomas.


METHODS
We performed a retrospective analysis of 71 patients who had undergone surgery for pituitary adenoma. Patient demographic, radiological, and histopathological features were correlated with HIF1A and ARID1A expression.


RESULTS
Most cases were HIF1A positive (62%). No significant correlation was found between HIF1A expression and age, gender, tumor size, bone erosion, hemorrhage, or Ki-67 index. An inverse correlation was demonstrated between HIF1A and cavernous sinus invasion (P = 0.035). ARID1A loss was found in 28.2% of pituitary adenomas. No significant correlation was found between ARID1A and any of the assessed variables.


CONCLUSIONS
In our patient cohort, we found that most pituitary adenomas expressed HIF1A. To the best of our knowledge, we are the first to assess the presence of ARID1A loss in pituitary adenomas, which occurred in 28.2% of cases. No individual demographic, imaging, or histopathological feature was predictive of ARID1A. Likewise, with the exception of an increased incidence of cavernous sinus invasion, no correlation was found with HIF1A. Given the prognostic value of these markers in other malignancies, their frequency in pituitary adenomas warrants further exploration of their potential role in pituitary adenoma treatment and outcome.
['Kinali|Burak|B|', 'Senoglu|Mehmet|M|', 'Karadag|Fatma Keklik|FK|', 'Karadag|Ali|A|', 'Middlebrooks|Erik H|EH|', 'Oksuz|Pinar|P|', 'Sandal|Evren|E|', 'Turk|Caglar|C|', 'Diniz|Gülden|G|']
D000236:Adenoma D000328:Adult D000368:Aged D015331:Cohort Studies D004268:DNA-Binding Proteins D005260:Female D006801:Humans D051795:Hypoxia-Inducible Factor 1, alpha Subunit D008279:Magnetic Resonance Imaging D008297:Male D008875:Middle Aged D009687:Nuclear Proteins D010911:Pituitary Neoplasms D011388:Prolactin D014157:Transcription Factors
Pituitary adenoma ARID1A Hypoxia-inducible factor 1 Immunohistochemistry α-subunit