{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T07:52:32Z","timestamp":1777362752677,"version":"3.51.4"},"reference-count":31,"publisher":"Scientific Scholar","content-domain":{"domain":["ijmr.org.in"],"crossmark-restriction":true},"short-container-title":["Indian J Med Res"],"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>Ocular surface squamous neoplasia (OSSN) encompasses a spectrum of tumours, including conjunctival squamous intraepithelial neoplasia (CSIN), carcinoma in situ (CIS), and invasive squamous cell carcinoma (iSCC). The roles of biomarkers such as epidermal growth factor receptor (EGFR), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1), and carbonic anhydrase IX (CAIX) in OSSN progression are incompletely understood. This study aimed to investigate their expression patterns in Asian Indian OSSN tumours.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This observational immunohistochemistry (IHC) study was conducted on 21 formalin-fixed, paraffin-embedded tissue specimens from patients with CSIN, CIS, or iSCC. OSSN tumours were categorised into Group A (CSIN and CIS) and Group B (iSCC). Immunohistochemical staining was used to assess the expression of EGFR, MMP-2, MMP-9, HIF-1\u03b1, and CAIX. Statistical analysis was performed to determine significant differences in biomarker expression between the groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Significantly higher expression of EGFR (\n                      <jats:italic>P<\/jats:italic>\n                      =0.03), MMP-2 (\n                      <jats:italic>P=<\/jats:italic>\n                      0.02), and CAIX (\n                      <jats:italic>P=<\/jats:italic>\n                      0.03) was observed in Group B (iSCC) compared to Group A (CSIN and CIS). MMP-9 expression did not differ significantly between the groups (\n                      <jats:italic>P=<\/jats:italic>\n                      0.14). HIF-1\u03b1 expression in tumour cells was also not significantly different (\n                      <jats:italic>P=<\/jats:italic>\n                      0.41). HIF-1\u03b1 expression in inflammatory cells was significantly higher in Group B (iSCC) compared to Group A (\n                      <jats:italic>P=<\/jats:italic>\n                      0.038).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation and conclusions<\/jats:title>\n                    <jats:p>This study suggests that EGFR, MMP-2, and CAIX may play a role in OSSN progression from CSIN\/CIS to iSCC. Elevated HIF-1\u03b1 expression in inflammatory cells highlights the potential involvement of inflammation in OSSN development. These biomarkers may serve as potential therapeutic targets and could also be integrated into diagnostic tools for OSSN.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.25259\/ijmr_2438_2025","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T07:06:43Z","timestamp":1777360003000},"page":"456-460","update-policy":"https:\/\/doi.org\/10.25259\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the significance of EGFR, MMP-2, MMP-9, HIF-1\u03b1, and CAIX as molecular biomarkers in ocular surface squamous neoplasia"],"prefix":"10.25259","volume":"163","author":[{"given":"Remya Girija","family":"Ramachandran","sequence":"first","affiliation":[{"name":"Department of L&T Ocular Pathology, Vision Research Foundation, Kamalnayan Bajaj Institute for Research in Vision and Ophthalmology, Chennai, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sowmya","family":"Parameswaran","sequence":"additional","affiliation":[{"name":"Department of Radheshyamkanoi Stem Cell Laboratory, Vision Research Foundation, Kamalnayan Bajaj Institute for Research in Vision and Ophthalmology, Chennai, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rama","family":"Rajagopal","sequence":"additional","affiliation":[{"name":"Department of Cornea, Medical and Vision Research Foundations, Sankara Nethralaya, Chennai, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jyotirmay","family":"Biswas","sequence":"additional","affiliation":[{"name":"Department of Uvea & Ocular Pathology, Medical and Vision Research Foundations, Sankara Nethralaya, Chennai, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subramanian","family":"Krishnakumar","sequence":"additional","affiliation":[{"name":"Department of L&T Ocular Pathology, Vision Research Foundation, Kamalnayan Bajaj Institute for Research in Vision and Ophthalmology, Chennai, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"10894","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"10.25259\/IJMR_2438_2025\/ref-1","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1038\/bjc.1996.581","article-title":"A review of the aetiology of squamous cell carcinoma of the conjunctiva","volume":"74","author":"Newton","year":"1996","journal-title":"Br J Cancer."},{"key":"10.25259\/IJMR_2438_2025\/ref-2","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.sjopt.2013.07.002","article-title":"Ocular surface squamous neoplasia \u2013 Review of etio-pathogenesis and an update on clinico-pathological diagnosis","volume":"27","author":"Mittal","year":"2013","journal-title":"Saudi J Ophthalmol."},{"key":"10.25259\/IJMR_2438_2025\/ref-3","first-page":"109","article-title":"Conjunctival tumors: Review of clinical features, risks, biomarkers, and outcomes \u2013 The 2017 J. Donald M. Gass Lecture","volume":"6","author":"Shields","year":"2017","journal-title":"Asia Pac J Ophthalmol."},{"key":"10.25259\/IJMR_2438_2025\/ref-4","doi-asserted-by":"publisher","first-page":"3571","DOI":"10.1007\/s10792-021-01939-2","article-title":"Spectrum of AS-OCT features of ocular surface tumors and correlation of clinico-tomographic features with histopathology: A study of 70 lesions","volume":"41","author":"Vempuluru","year":"2021","journal-title":"Int Ophthalmol."},{"key":"10.25259\/IJMR_2438_2025\/ref-5","doi-asserted-by":"publisher","first-page":"e000829","DOI":"10.1136\/bmjophth-2021-000829","article-title":"Ocular surface angiography: From neovessels to neoplasia","volume":"6","author":"Steger","year":"2021","journal-title":"BMJ Open Ophthalmol."},{"key":"10.25259\/IJMR_2438_2025\/ref-6","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.jtos.2013.11.001","article-title":"Ultra high-resolution anterior segment optical coherence tomography in the diagnosis and management of ocular surface squamous neoplasia","volume":"12","author":"Thomas","year":"2014","journal-title":"Ocul Surf."},{"key":"10.25259\/IJMR_2438_2025\/ref-7","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1001\/archopht.1982.01030030111011","article-title":"Invasive squamous cell carcinoma with intraocular mucoepidermoid features","volume":"100","author":"Searl","year":"1982","journal-title":"Arch Ophthalmol."},{"key":"10.25259\/IJMR_2438_2025\/ref-8","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/modpathol.2016.41","article-title":"Altered gene expression in conjunctival squamous cell carcinoma","volume":"29","author":"Mahale","year":"2016","journal-title":"Mod Pathol."},{"key":"10.25259\/IJMR_2438_2025\/ref-9","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.jtos.2013.01.006","article-title":"Matrix metalloproteinases and their inhibitors in squamous cell carcinoma of the conjunctiva","volume":"11","author":"Di Girolamo","year":"2013","journal-title":"Ocul Surf."},{"key":"10.25259\/IJMR_2438_2025\/ref-10","doi-asserted-by":"publisher","first-page":"e93164","DOI":"10.1371\/journal.pone.0093164","article-title":"LRIG1 as a potential novel marker for neoplastic transformation in ocular surface squamous neoplasia","volume":"9","author":"Nagata","year":"2014","journal-title":"PLoS One."},{"key":"10.25259\/IJMR_2438_2025\/ref-11","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1097\/01.iop.0000202609.92772.c3","article-title":"Expression of the epidermal growth factor receptor in conjunctival squamous cell carcinoma","volume":"22","author":"Shepler","year":"2006","journal-title":"Ophthalmic Plast Reconstr Surg."},{"key":"10.25259\/IJMR_2438_2025\/ref-12","doi-asserted-by":"publisher","first-page":"e0238120","DOI":"10.1371\/journal.pone.0238120","article-title":"Expression, intracellular localization, and mutation of EGFR in conjunctival squamous cell carcinoma and the association with prognosis and treatment","volume":"15","author":"Sakai","year":"2020","journal-title":"PLoS One."},{"key":"10.25259\/IJMR_2438_2025\/ref-13","doi-asserted-by":"publisher","first-page":"1608","DOI":"10.1001\/archophthalmol.2012.2515","article-title":"Epidermal growth factor receptor inhibitors for treatment of orbital squamous cell carcinoma","volume":"130","author":"El-Sawy","year":"2012","journal-title":"Arch Ophthalmol."},{"key":"10.25259\/IJMR_2438_2025\/ref-14","doi-asserted-by":"crossref","first-page":"5101","DOI":"10.3390\/ijms26115101","article-title":"HIF-1\u03b1-mediated disruption of cellular junctions: The impact of hypoxia on the tumor microenvironment and invasion","volume":"26","author":"Springer","year":"2025","journal-title":"Int J Mol"},{"key":"10.25259\/IJMR_2438_2025\/ref-15","doi-asserted-by":"publisher","first-page":"3297","DOI":"10.3390\/cancers14143297","article-title":"Cancer therapeutic targeting of hypoxia induced carbonic anhydrase IX: From bench to bedside","volume":"14","author":"McDonald","year":"2022","journal-title":"Cancers (Basel)."},{"key":"10.25259\/IJMR_2438_2025\/ref-16","doi-asserted-by":"publisher","first-page":"3313","DOI":"10.3390\/ijms25063313","article-title":"A molecular perspective on HIF-1\u03b1 and angiogenic stimulator networks and their role in solid tumors: An update","volume":"25","author":"Magar","year":"2024","journal-title":"Int J Mol Sci."},{"key":"10.25259\/IJMR_2438_2025\/ref-17","doi-asserted-by":"publisher","first-page":"e70700","DOI":"10.7759\/cureus.70700","article-title":"Hypoxia-inducible factor 1-alpha (HIF-1\u03b1) and cancer: Mechanisms of tumor hypoxia and therapeutic targeting","volume":"16","author":"Basheeruddin","year":"2024","journal-title":"Cureus."},{"key":"10.25259\/IJMR_2438_2025\/ref-18","doi-asserted-by":"publisher","first-page":"693","DOI":"10.3390\/cells14100693","article-title":"Cooperative role of carbonic anhydrase IX\/XII in driving tumor invasion and metastasis: A novel targeted therapeutic strategy","volume":"14","author":"Yang","year":"2025","journal-title":"Cells."},{"key":"10.25259\/IJMR_2438_2025\/ref-19","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1186\/s13000-014-0221-9","article-title":"Different approaches for interpretation and reporting of immunohistochemistry analysis results in bone tissue \u2013 A review","volume":"9","author":"Fedchenko","year":"2014","journal-title":"Diagn Pathol."},{"key":"10.25259\/IJMR_2438_2025\/ref-20","doi-asserted-by":"publisher","first-page":"83","DOI":"10.2147\/HP.S93413","article-title":"The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy","volume":"3","author":"Muz","year":"2015","journal-title":"Hypoxia (Auckl)."},{"key":"10.25259\/IJMR_2438_2025\/ref-21","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.lungcan.2005.03.036","article-title":"Expression of HIF-1\u03b1, CA IX, VEGF, and MMP-9 in surgically resected non-small cell lung cancer","volume":"49","author":"Kim","year":"2005","journal-title":"Lung Cancer."},{"key":"10.25259\/IJMR_2438_2025\/ref-23","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.1007\/s00417-020-04734-4","article-title":"HIF-1\u03b1, HIF-2\u03b1, and ProExC: Diagnostic or prognostic relevance in conjunctival intraepithelial neoplasia? Graefes Arch Clin Exp Ophthalmol","volume":"258","author":"Nuessle","year":"2020"},{"key":"10.25259\/IJMR_2438_2025\/ref-24","first-page":"731","article-title":"Ocular surface squamous neoplasia in 501 cases: Comparative analysis of clinical features, outcomes, and prognostic factors","volume":"27","author":"Anand","year":"2013","journal-title":"Eye (Lond)."},{"key":"10.25259\/IJMR_2438_2025\/ref-25","doi-asserted-by":"publisher","first-page":"1974","DOI":"10.1016\/j.ophtha.2012.04.022","article-title":"Predictors of ocular surface squamous neoplasia recurrence after excisional surgery","volume":"119","author":"Galor","year":"2012","journal-title":"Ophthalmology."},{"key":"10.25259\/IJMR_2438_2025\/ref-26","first-page":"482","article-title":"Expression of epidermal growth factor receptor and matrix metalloproteinase-2 in ocular surface squamous neoplasia","volume":"64","author":"Chauhan","year":"2021","journal-title":"Indian J Pathol Microbiol."},{"key":"10.25259\/IJMR_2438_2025\/ref-27","first-page":"79","article-title":"Overview of epidermal growth factor receptor inhibitors in oncology","volume":"34","author":"Li","year":"2008","journal-title":"Cancer Treat Rev."},{"key":"10.25259\/IJMR_2438_2025\/ref-28","doi-asserted-by":"publisher","first-page":"2387","DOI":"10.1126\/science.1067100","article-title":"Matrix metalloproteinase inhibitors and cancer: Trials and tribulations","volume":"295","author":"Coussens","year":"2002","journal-title":"Science."},{"key":"10.25259\/IJMR_2438_2025\/ref-29","doi-asserted-by":"publisher","first-page":"6642","DOI":"10.1038\/sj.onc.1204097","article-title":"Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment","volume":"19","author":"Zucker","year":"2000","journal-title":"Oncogene."},{"key":"10.25259\/IJMR_2438_2025\/ref-30","first-page":"1","article-title":"Hypoxia-inducible carbonic anhydrase IX and cancer: From bench to bedside","volume":"354","author":"Chiche","year":"2009","journal-title":"Cancer Lett"},{"key":"10.25259\/IJMR_2438_2025\/ref-31","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1097\/01.ju.0000165693.68449.c3","article-title":"Renal cell carcinoma 2005: New frontiers in staging, prognostication and targeted molecular therapy","volume":"173","author":"Lam","year":"2005","journal-title":"J Urol."},{"key":"10.25259\/IJMR_2438_2025\/ref-32","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1097\/IIO.0000000000000050","article-title":"Ocular surface squamous neoplasia: evidence for topical chemotherapy","volume":"55","author":"Pe\u2019er","year":"2015 Winter","journal-title":"Int Ophthalmol Clin"}],"container-title":["The Indian Journal of Medical Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ijmr.org.in\/exploring-the-significance-of-egfr-mmp-2-mmp-9-hif-1-and-caix-as-molecular-biomarkers-in-ocular-surface-squamous-neoplasia\/","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/ijmr.org.in\/exploring-the-significance-of-egfr-mmp-2-mmp-9-hif-1-and-caix-as-molecular-biomarkers-in-ocular-surface-squamous-neoplasia\/","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T07:06:44Z","timestamp":1777360004000},"score":1,"resource":{"primary":{"URL":"http:\/\/ijmr.org.in\/exploring-the-significance-of-egfr-mmp-2-mmp-9-hif-1-and-caix-as-molecular-biomarkers-in-ocular-surface-squamous-neoplasia\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,27]]},"references-count":31,"alternative-id":["10.25259\/IJMR_2438_2025"],"URL":"https:\/\/doi.org\/10.25259\/ijmr_2438_2025","relation":{},"ISSN":["0971-5916"],"issn-type":[{"value":"0971-5916","type":"print"}],"subject":[],"published":{"date-parts":[[2026,4,27]]},"article-number":"456"}}