Molecular biological analysis of pituitary apoplexy induced by hypoxic stimulation in pituitary adenoma

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Hypoxia, which is involved in a wide range of biological processes, has been extensively investigated in malignant tumors. The role and mechanism of hypoxia in benign tumors, in particular pituitaiy adenomas, is well understood. Some studies indicate that pituitary adenoma tissues are hypovascular and have lower oxygen saturation relative to the normal pituitary gland and suggest that this may induce hypoxia. Our previous study showed that laminin beta 2 mRNA is upregnlated under hypoxic conditions (1% oxygen) but not under normoxic conditions (21% oxygen) in the HP-75 cell line. In the present study, we further investigated the expression of laminin beta 1, 2 or 3 chains, under hypoxic and normoxic conditions in HP-75 cells using Western blotting. We found that only laminin beta 2 had a significantly higher expression under hypoxia than under normoxia in the HP-75 cell line. The expression of laminin beta chains was investigated by fluorescent immunohistochemistry of paraffin-embedded sections of tissue from the pituitary adenomas of 42 cases (30 cases without apoplexy and 12 with apoplexy) categorized according to Knosp grading and tumor size. We found that only laminin beta 2 expression correlated significantly with tumor size and apoplexy, but did not correlate with invasiveness. In conclusion, laminin beta 2 can be regarded as a surrogate marker of hypoxia as its levels are significantly elevated under hypoxic conditions, and it is the predominant beta chain expressed in invasive pituitary adenomas, macroadenomas, and apoplexy.