{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T09:07:45Z","timestamp":1789117665930,"version":"build-2803163510"},"reference-count":32,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"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>Introduction: Salvage surgery is known for an increased surgical complication rate. However, currently available patient, tumor and therapy factors are not reliable enough to predict surgical site complications (SSCs). This exploratory study tests skin acquired by neck dissection for several histochemical and immunohistochemical stains to explore tissue changes related to wound healing. Patients and methods: From an existing database of 232 isolated neck dissections (NDs), 17 patients who underwent skin resection during ND were included\u20145 who underwent primary procedures and 12 who underwent salvage procedures. Skin specimens were tested for ten histochemical and immunohistochemical stains, with emphasis on the stages of wound healing: inflammation, proliferation and remodeling. Results: Three stains (CD-68, \u03b1-SMA, and Vimentin) showed significantly different expression between the primary surgical and salvage groups (respectively. p = 0.013, p = 0.044 and p = 0.015), without a clear pattern of decreased or increased expression. None of the ten stains showed a significant difference related to SSCs. Conclusions: The three significantly different staining patterns found in this exploratory study can all be linked to macrophage and (myo-)fibroblast transitions, possibly representing an imbalance of macrophage\/stroma interplay. Future studies focusing on the role of macrophages in wound healing after salvage surgery are necessary.<\/jats:p>","DOI":"10.3390\/cancers18182942","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T08:17:42Z","timestamp":1789114662000},"page":"2942","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Expression of Wound-Healing-Related Histochemical and Immunohistochemical Stains at the Time of Salvage Isolated Neck Dissection\u2014An Exploratory Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4908-2815","authenticated-orcid":false,"given":"Roel","family":"Henneman","sequence":"first","affiliation":[{"name":"Department of Head and Neck Oncology and Surgery, Netherlands Cancer Institute, 1006 BE Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0551-7813","authenticated-orcid":false,"given":"Joyce","family":"Sanders","sequence":"additional","affiliation":[{"name":"Department of Pathology, Netherlands Cancer Institute, 1006 BE Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Ingrid","family":"Hofland","sequence":"additional","affiliation":[{"name":"Core Facility Molecular Pathology and Biobanking, Netherlands Cancer Institute, 1006 BE Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5928-4704","authenticated-orcid":false,"given":"Olga","family":"Hamming-Vrieze","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Netherlands Cancer Institute, 1006 BE Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Alfons J. M.","family":"Balm","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Oncology and Surgery, Netherlands Cancer Institute, 1006 BE Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erienne","family":"de Cuba","sequence":"additional","affiliation":[{"name":"Department of Pathology, Netherlands Cancer Institute, 1006 BE Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1177\/01945998211000438","article-title":"Surgeon Volume and Complications in Lateral Neck Dissection for Squamous Cell Carcinoma: A Multidatabase Analysis","volume":"165","author":"Campbell","year":"2021","journal-title":"Otolaryngol. Neck Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.ejso.2020.10.015","article-title":"Surgical site complications of post-chemoradiotherapy neck dissection: Urgent need for standard registration","volume":"47","author":"Henneman","year":"2021","journal-title":"Eur. J. Surg. Oncol. (EJSO)"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1016\/j.jacc.2009.11.053","article-title":"Understanding Radiation-Induced Vascular Disease","volume":"55","author":"Weintraub","year":"2010","journal-title":"JACC"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1007\/s00432-015-1974-6","article-title":"Radiation-induced fibrosis: Mechanisms and implications for therapy","volume":"141","author":"Straub","year":"2015","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.joms.2013.11.010","article-title":"Prophylactic Chimera Anterolateral Thigh\/Vastus Lateralis Flap: Preventing Complications in High-Risk Head and Neck Reconstruction","volume":"72","author":"Cordova","year":"2014","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_6","first-page":"E2317","article-title":"Efficacy of pectoralis major muscle flap for pharyngocutaneous fistula prevention in salvage total laryngectomy: A systematic review","volume":"38","author":"Aires","year":"2015","journal-title":"Head Neck"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.ejso.2022.12.010","article-title":"Surgical site complications of isolated salvage neck dissection post-radiotherapy and post-chemoradiotherapy\u2014A cohort analysis (1997\u20132017)","volume":"49","author":"Henneman","year":"2022","journal-title":"Eur. J. Surg. Oncol. (EJSO)"},{"key":"ref_8","first-page":"1492","article-title":"The ALK-1\/Smad1 pathway in cardiovascular physiopathology. A new target for therapy?","volume":"1832","year":"2013","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Basis Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1634\/theoncologist.2009-S101","article-title":"Targeting the TGF-\u03b21 Pathway to Prevent Normal Tissue Injury After Cancer Therapy","volume":"15","author":"Anscher","year":"2010","journal-title":"Oncologist"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.imbio.2011.01.001","article-title":"Macrophages in skin injury and repair","volume":"216","author":"Delavary","year":"2011","journal-title":"Immunobiology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1369\/jhc.7A7287.2007","article-title":"An Immunohistochemical Method for Identifying Fibroblasts in Formalin-fixed, Paraffin-embedded Tissue","volume":"56","author":"Goodpaster","year":"2007","journal-title":"J. Histochem. Cytochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/j.1365-3083.2008.02091.x","article-title":"Expression of CD68 in Non-Myeloid Cell Types","volume":"67","author":"Gottfried","year":"2008","journal-title":"Scand. J. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e99911","DOI":"10.1172\/jci.insight.99911","article-title":"The evolving relationship of wound healing and tumor stroma","volume":"3","author":"Foster","year":"2018","journal-title":"JCI Insight"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"E4320","DOI":"10.1073\/pnas.1519197113","article-title":"Vimentin coordinates fibroblast proliferation and keratinocyte differentiation in wound healing via TGF-\u03b2\u2013Slug signaling","volume":"113","author":"Cheng","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1002\/stem.1661","article-title":"Concise Review: Evidence for CD34 as a Common Marker for Diverse Progenitors","volume":"32","author":"Sidney","year":"2014","journal-title":"Stem Cells"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"42","DOI":"10.32098\/mltj.01.2013.07","article-title":"Tendon structure and extracellular matrix components are affected by spasticity in cerebral palsy patients","volume":"3","author":"Gagliano","year":"2019","journal-title":"Muscle Ligaments Tendons J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1369\/jhc.2009.953067","article-title":"Intralobular Pulmonary Lymphatic Distribution in Normal Human Lung Using D2-40 Antipodoplanin Immunostaining","volume":"57","author":"Kambouchner","year":"2009","journal-title":"J. Histochem. Cytochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1159\/000218336","article-title":"Increased Connective Tissue Extracellular Matrix in the op\/op Model of Osteopetrosis","volume":"76","author":"Radi","year":"2009","journal-title":"Pathobiology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1269\/jrr.09066","article-title":"Recombinant human epidermal growth factor accelerates the proliferation of irradiated human fibroblasts and keratinocytes in vitro and in vivo","volume":"50","author":"Ryu","year":"2009","journal-title":"J. Radiat. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1111\/j.1365-2559.2006.02533.x","article-title":"Routine elastic staining assists detection of vascular invasion in colorectal cancer","volume":"49","author":"Abdulkader","year":"2006","journal-title":"Histopathology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/path.1074","article-title":"Skin flap-induced regression of granulation tissue correlates with reduced growth factor and increased metalloproteinase expression","volume":"197","author":"Darby","year":"2002","journal-title":"J. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.bbadis.2016.11.006","article-title":"The role of \u03b1-smooth muscle actin in fibroblast-mediated matrix contraction and remodeling","volume":"1863","author":"Shinde","year":"2017","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Basis Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1165\/rcmb.2003-0063OC","article-title":"Smad3 Mediates Transforming Growth Factor-\u03b2\u2013Induced \u03b1-Smooth Muscle Actin Expression","volume":"29","author":"Hu","year":"2003","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/s00403-002-0306-2","article-title":"Increased expression of collagen types I and III in human skin as a consequence of radiotherapy","volume":"294","author":"Riekki","year":"2002","journal-title":"Arch. Dermatol. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4133","DOI":"10.1096\/fj.09-151449","article-title":"Unique and redundant functions of integrins in the epidermis","volume":"24","author":"Margadant","year":"2010","journal-title":"FASEB J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1159\/000166997","article-title":"Immunohistochemical Comparison of Markers for Wound Healing on Plastic-Embedded and Frozen Mucosal Tissue","volume":"190","author":"Mai","year":"2008","journal-title":"Cells Tissues Organs"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.forsciint.2014.11.013","article-title":"Analysis of morphological characteristics and expression levels of extracellular matrix proteins in skin wounds to determine wound age in living subjects in forensic medicine","volume":"246","author":"Fronczek","year":"2015","journal-title":"Forensic Sci. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1002\/path.5632","article-title":"Macrophage\u2013stroma interactions in fibrosis: Biochemical, biophysical, and cellular perspectives","volume":"254","author":"Vasse","year":"2021","journal-title":"J. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1681\/ASN.2016050573","article-title":"Macrophage-to-Myofibroblast Transition Contributes to Interstitial Fibrosis in Chronic Renal Allograft Injury","volume":"28","author":"Wang","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1186\/s40169-015-0046-5","article-title":"Hallmarks of epithelial to mesenchymal transition are detectable in Crohn\u2019s disease associated intestinal fibrosis","volume":"4","author":"Scharl","year":"2015","journal-title":"Clin. Transl. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1091\/mbc.E17-06-0364","article-title":"In wound repair vimentin mediates the transition of mesenchymal leader cells to a myofibroblast phenotype","volume":"29","author":"Walker","year":"2018","journal-title":"Mol. Biol. Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1007\/s12105-020-01188-2","article-title":"Pericyte in Oral Squamous Cell Carcinoma: A Systematic Review","volume":"14","author":"Valle","year":"2020","journal-title":"Head Neck Pathol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/18\/2942\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T08:31:06Z","timestamp":1789115466000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/18\/2942"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":32,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cancers18182942"],"URL":"https:\/\/doi.org\/10.3390\/cancers18182942","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]}}}