Exploring the significance of EGFR, MMP-2, MMP-9, HIF-1α, and CAIX as molecular biomarkers in ocular surface squamous neoplasia

Background and objectives 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-1α (HIF-1α), and carbonic anhydrase IX (CAIX) in OSSN progression are incompletely understood. This study aimed to investigate their expression patterns in Asian Indian OSSN tumours. Methods 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-1α, and CAIX. Statistical analysis was performed to determine significant differences in biomarker expression between the groups. Results Significantly higher expression of EGFR ( P =0.03), MMP-2 ( P= 0.02), and CAIX ( P= 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 ( P= 0.14). HIF-1α expression in tumour cells was also not significantly different ( P= 0.41). HIF-1α expression in inflammatory cells was significantly higher in Group B (iSCC) compared to Group A ( P= 0.038). Interpretation and conclusions This study suggests that EGFR, MMP-2, and CAIX may play a role in OSSN progression from CSIN/CIS to iSCC. Elevated HIF-1α 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.

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Journal
The Indian Journal of Medical Research
Published
2026-04-27
DOI
https://doi.org/10.25259/ijmr_2438_2025
Primary Topic
Ocular Oncology and Treatments
Type
article
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article

Exploring the significance of EGFR, MMP-2, MMP-9, HIF-1α, and CAIX as molecular biomarkers in ocular surface squamous neoplasia

Rama Rajagopal, Sowmya Parameswaran, Remya Girija Ramachandran, Subramanian Krishnakumar et al.
The Indian Journal of Medical Research
Ocular Oncology and Treatments
article

Exploring the significance of EGFR, MMP-2, MMP-9, HIF-1α, and CAIX as molecular biomarkers in ocular surface squamous neoplasia

Rama Rajagopal, Sowmya Parameswaran, Remya Girija Ramachandran, Subramanian Krishnakumar, Jyotirmay Biswas
article en

Abstract

Background and objectives 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-1α (HIF-1α), and carbonic anhydrase IX (CAIX) in OSSN progression are incompletely understood. This study aimed to investigate their expression patterns in Asian Indian OSSN tumours. Methods 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-1α, and CAIX. Statistical analysis was performed to determine significant differences in biomarker expression between the groups. Results Significantly higher expression of EGFR ( P =0.03), MMP-2 ( P= 0.02), and CAIX ( P= 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 ( P= 0.14). HIF-1α expression in tumour cells was also not significantly different ( P= 0.41). HIF-1α expression in inflammatory cells was significantly higher in Group B (iSCC) compared to Group A ( P= 0.038). Interpretation and conclusions This study suggests that EGFR, MMP-2, and CAIX may play a role in OSSN progression from CSIN/CIS to iSCC. Elevated HIF-1α 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.

The Indian Journal of Medical ResearchVol. 163
Sankara Nethralaya (IN), Oil and Natural Gas Corporation (India) (IN)
Openalex Percentile: Top 4%
Ocular Oncology and Treatments
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