Integrin αvβ6 Expression in Parathyroid Adenomas and Adjacent Non-Neoplastic Parathyroid Tissue: Immunohistochemical Rationale for Integrin αvβ6-Targeted PET Imaging

Background: Accurate preoperative localization of hyperfunctioning parathyroid tissue is essential for focused parathyroid surgery; however, localization remains challenging in a subset of patients with small, ectopic, multiglandular, or conventionally occult lesions. 68Ga-Trivehexin targets integrin αvβ6 and has shown promising clinical performance in primary hyperparathyroidism; however, the immunohistochemical distribution of the integrin αvβ6 in parathyroid adenomas and non-neoplastic parathyroid tissue remains insufficiently characterized. Methods: Integrin αvβ6 expression was assessed immunohistochemically in 56 surgically resected parathyroid adenomas. Adjacent morphologically non-neoplastic parathyroid tissue was available in 51 cases and served as a paired comparator. Only membranous staining was scored. Staining intensity was categorized as 0, 1+ (weak), 2+ (moderate), or 3+ (strong), and the percentage of cells at each intensity was recorded. A weighted integrin αvβ6 expression score was calculated as (1 ×% weak) + (2 ×% moderate) + (3 ×% strong), yielding a range of 0–300. Paired comparisons were performed, and correlations with adenoma dimensions were assessed. Results: Forty-five of 56 adenomas (80.4%) and 48 of 51 adjacent non-neoplastic samples (94.1%) met the predefined positivity criterion. The median integrin αvβ6-positive cell fraction and weighted score were 42.5% (interquartile range (IQR) 9.5–90.0%) and 60 (IQR, 10–140), respectively. The corresponding values in adjacent tissue were 50% (IQR, 20–80%) and 60 (IQR, 30–115), respectively. Neither the weighted score nor the total positive-cell fraction differed significantly in paired analyses (Wilcoxon p = 0.902 and p = 0.442, respectively). Categorical positivity also did not differ significantly (exact McNemar p = 0.065). Crucially, the distribution of staining intensity differed between the compartments: a strong (3+) component was present in 19/56 adenomas (33.9%), but in only 3/51 adjacent samples (5.9%). In exploratory paired analysis, the proportion of strongly stained cells was higher in adenomas (Wilcoxon p = 0.0015). Integrin αvβ6 expression was not significantly associated with adenoma dimension. Conclusions: Integrin αvβ6 is a common membranous phenotype in both parathyroid adenomas and adjacent non-neoplastic parathyroid tissue and therefore should not be regarded as adenoma-specific. Nevertheless, adenomas more frequently contain strongly integrin αvβ6-positive cell populations, indicating a redistribution of expression intensity rather than a simple increase in overall positivity or weighted expression. These findings provide tissue-level support for integrin αvβ6-targeted parathyroid imaging and offer a plausible histopathological framework for the encouraging clinical performance of 68Ga-Trivehexin PET/CT. Prospective, lesion-matched studies integrating immunohistochemistry, PET metrics, lesion volume, operative findings, and histological confirmation are now required to validate these observations.