Parenchymal and stromal adaptations to hypoxia in adenoid cystic carcinoma and mucoepidermoid carcinoma: a comparative immunohistochemical analysis of HIF-1α, NOTCH-1, ADAM-12 and HB-EGF.

OBJECTIVE

To evaluate the expression of hypoxia-inducible factor 1 alpha (HIF-1α), NOTCH-1, ADAM-12, and heparin-binding epidermal growth factor (HB-EGF) in adenoid cystic carcinoma (ACC), mucoepidermoid carcinoma (MEC), and normal salivary glands (SG), exploring hypoxia-related stromal and parenchymal adaptations with potential implications for tumor stratification and therapeutic targeting.

STUDY

DESIGN

Forty-six formalin-fixed, paraffin-embedded samples were analyzed: 17 ACC, 19 MEC, and 10 SG controls. Immunohistochemistry was performed for all markers. Protein expression was quantified as percentage of positive labeling area in both parenchymal and stromal compartments. Statistical comparisons were conducted using the Kruskal-Wallis test followed by Dunn's posthoc test with Holm correction (P < .05).

RESULTS

All proteins demonstrated significantly higher parenchymal expression in ACC and MEC compared with SG (all P ≤ .002), without significant differences between tumor types. In the stromal compartment, HB-EGF expression was higher in MEC than ACC (P < .0001), whereas HIF-1α expression was higher in ACC than MEC (P < .0001). ADAM-12 and NOTCH-1 were increased in tumor stroma relative to SG but did not differ between ACC and MEC.

CONCLUSIONS

Hypoxia-related proteins exhibit compartment-specific patterns that distinguish ACC from MEC at the stromal level, supporting molecular stratification and potential targeted approaches in SG carcinomas.