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. 2022 Apr 27;19(9):5298.
doi: 10.3390/ijerph19095298.

Expression of VEGF, EGF, and Their Receptors in Squamous Esophageal Mucosa, with Correlations to Histological Findings and Endoscopic Minimal Changes, in Patients with Different GERD Phenotypes

Affiliations

Expression of VEGF, EGF, and Their Receptors in Squamous Esophageal Mucosa, with Correlations to Histological Findings and Endoscopic Minimal Changes, in Patients with Different GERD Phenotypes

Justyna Wasielica-Berger et al. Int J Environ Res Public Health. .

Abstract

Background: Gastroesophageal reflux disease (GERD) may present as nonerosive reflux disease (NERD), erosive esophagitis (EE), or be complicated by Barrett's esophagus (BE). The explanation as to what determines the phenotype of GERD is awaited. Therefore, we assessed the correlation between the growth factors expression and endoscopic as histologic findings in GERD patients.

Methods: The squamous esophageal epithelium of 50 patients (20-NERD, 7-EE, 15-BE, 8 controls) was examined by: (1) magnification endoscopy with evaluation of minimal GERD changes such as: microerosions, white spots, palisade blood vessels visibility, and intrapapillary capillary loops (IPCLs) appearance, (2) histology, (3) immunohistochemistry with evaluation of the expression of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and their receptors (VEGFR and EGFR).

Results: The expression of VEGF, but not VEGFR, EGF, and EGFR, was significantly increased in EE patients compared to NERD patients and controls. VEGF levels correlated significantly with the presence of white spots, but not with other minimal endoscopic and histologic features. The EGFR expression correlated positively with basal cell hyperplasia and enlarged IPCLs.

Conclusions: Our findings suggest a correlation between growth factors expression and findings in conventional endoscopy, formation of endoscopic minimal changes, and histologic lesions.

Keywords: EGF; GERD; VEGF; growth factors; minimal change esophagitis.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Study design.
Figure 2
Figure 2
Normal squamous mucosa and minimal changes characteristic of GERD in magnifying endoscopy. (A)—normal squamous mucosa: palisade vessels clearly visible, no enlarged intrapapillary capillary loops (IPCLs); (B)—microerosion pointed by blue arrow, enlarged IPCLs in the background; (C)—enlarged IPCLs, palisade vessels obscured; (D)—elongated IPCLs; (E)—white spots encircling enlarged IPCLs; (F)—enlarged IPCLs (right side of picture) and white spots visible regardless of IPCLs (left side of the picture); (G)—white spots; (H)—palisade vessels obscured.
Figure 3
Figure 3
The expression of VEGF and VEGFR in esophageal squamous mucosa evaluated by immunohistochemistry. (A)—low VEGF expression (positive in less than 33% of vessels) (magn. ×400); (B)—high VEGF expression (positive in over 66% of vessels) (magn. ×400); (C)—low VEGFR expression (positive in less than 33% of vessels) (magn. ×200); (D)—high VEGFR expression (positive in over 66% of vessels) (magn. ×400).
Figure 4
Figure 4
The expression of EGF and EGFR in squamous epithelium evaluated by immunohistochemistry. (A)—low EGF expression (positive in less than 33% of vessels and no reaction in squamous epithelium) (magn. ×200); (B)—high EGF expression (positive in over 66% of vessels and positive reaction in more than a half of the thickness of the squamous epithelium) (magn. ×200); (C)—high EGFR expression (positive in over 66% of vessels and positive reaction in more than a half of the thickness of the squamous epithelium) (magn. ×200). There were no cases with low EGFR expression in the study group.
Figure 5
Figure 5
The expression of growth factors in squamous epithelium of patients with Barrett’s esophagus (BE), erosive esophagitis (EE), nonerosive reflux disease (NERD), and healthy controls. (A)—VEGF, (B)—VEGFR, (C)—EGF, (D)—EGFR. VEGF expression was significantly higher in EE than in NERD and control group. Other differences were not significant.

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