{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T14:01:14Z","timestamp":1789999274595,"version":"4.0.1"},"reference-count":31,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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 \u03b1v\u03b26 and has shown promising clinical performance in primary hyperparathyroidism; however, the immunohistochemical distribution of the integrin \u03b1v\u03b26 in parathyroid adenomas and non-neoplastic parathyroid tissue remains insufficiently characterized. Methods: Integrin \u03b1v\u03b26 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 \u03b1v\u03b26 expression score was calculated as (1 \u00d7% weak) + (2 \u00d7% moderate) + (3 \u00d7% strong), yielding a range of 0\u2013300. 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 \u03b1v\u03b26-positive cell fraction and weighted score were 42.5% (interquartile range (IQR) 9.5\u201390.0%) and 60 (IQR, 10\u2013140), respectively. The corresponding values in adjacent tissue were 50% (IQR, 20\u201380%) and 60 (IQR, 30\u2013115), 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 \u03b1v\u03b26 expression was not significantly associated with adenoma dimension. Conclusions: Integrin \u03b1v\u03b26 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 \u03b1v\u03b26-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 \u03b1v\u03b26-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.<\/jats:p>","DOI":"10.3390\/cancers18183026","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:50:03Z","timestamp":1789995003000},"page":"3026","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrin \u03b1v\u03b26 Expression in Parathyroid Adenomas and Adjacent Non-Neoplastic Parathyroid Tissue: Immunohistochemical Rationale for Integrin \u03b1v\u03b26-Targeted PET Imaging"],"prefix":"10.3390","volume":"18","author":[{"given":"Amro","family":"Tuffaha","sequence":"first","affiliation":[{"name":"Medical Clinic, Medical University Lausitz-Carl-Thiem, 03048 Cottbus, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2352-4435","authenticated-orcid":false,"given":"Wael","family":"Hananeh","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology and Public Health, Faculty of Veterinary Medicine, University of Science and Technology, Irbid 22110, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Mario","family":"Liese","sequence":"additional","affiliation":[{"name":"Surgical Clinic, Oder Spree Krankenhaus, 15848 Beeskow, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Dai","family":"Que Vu","sequence":"additional","affiliation":[{"name":"Surgical Clinic, Medical University Lausitz-Carl-Thiem, 03048 Cottbus, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Muin","family":"Tuffaha","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Medical University Lausitz-Carl-Thiem, 03048 Cottbus, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8753-6347","authenticated-orcid":false,"given":"Michael","family":"Starke","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Medical University Lausitz-Carl-Thiem, 03048 Cottbus, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1001\/jamaoto.2022.4421","article-title":"Emerging Imaging Technologies for Parathyroid Gland Identification and Vascular Assessment in Thyroid Surgery: A Review from the American Head and Neck Society Endocrine Surgery Section","volume":"149","author":"Triponez","year":"2023","journal-title":"JAMA Otolaryngol. 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