HIF-1α, HIF-2α, and ProExC: diagnostic or prognostic relevance in conjunctival intraepithelial neoplasia?

Abstract

The aim of this study was to investigate HIF-1α, HIF-2α, and ProExC expression in conjunctival intraepithelial neoplasia (CIN), to differentiate between metaplasia and dysplasia, and to access their value as diagnostic and prognostic immunohistochemical markers. Recurrence and progression into SCC (squamous cell carcinoma) were defined as endpoints. Methods Forty-three specimens including CIN I (2), CIN II (9), CIN III (29), with and without metaplasia, and metaplasia alone (3), as well as 21 conjunctival control specimens, were stained with antibodies against HIF-1α, HIF-2α, and ProExC. The percentage of positively stained cells were calculated and used for further analysis. Results The mean percentages of HIF-1α and HIF-2α were not increased in CIN. In comparison, the expressions of these markers were even significantly elevated in control specimens (p < 0.001). Upper epithelial cells in CIN were more often ProExC-positive compared with normal conjunctiva or metaplasia (p = 0.06 and p = 0.07). Cox proportional-hazards analysis was performed for characterization of factors influencing the combined endpoint and showed a significant elevated hazard ratio for staining with ProExC (p = 0.04) compared with HIF-1α (p = 0.26) and HIF-2α (p = 0.49). Conclusion Our study shows that HIF-1α and HIF-2α do not serve as diagnostic or prognostic markers in CIN. ProExC seems to be a potential indicator for CIN, but not a reliable diagnostic marker. However, control specimens occasionally also display a high percentage of ProExC-positive cells and staining over the entire epithelial layer.

Expression of thrombospondin-1 in conjunctival squamous cell carcinoma is correlated to the Ki67 index and associated with progression-free survival

“…With regard to prognosis and treatment associated with molecular biological markers, other studies have examined the use of hypoxia-inducible factor-α (HIF-α) as a potential marker. [20] However, in the present study, HIF-α staining was not confirmed in preliminary our experiment(data not shown) and thus could not be used to obtain additional knowledge. Daubon et al reported that transforming growth factor 1 induced thrombospondin-1 expression via Smad3, which contributes to the invasive behavior during expansion found in glioblastoma development.…”

HIF1α and HIF2α immunoreactivity in epithelial tissue of primary and recurrent pterygium by immunohistochemical analysis

“…For instance, traumatic brain injury in rats resulted in significant HIF1α elevation detected as early as 1 h after the trauma [ 22 ]. We had found similar results when immunohistochemically comparing immunoreactivity of both HIF isoforms in conjunctival intraepithelial neoplasia (CIN) and in healthy conjunctiva, and assumed that HIF is downregulated in CIN to avoid cell cycle arrest and HIF-induced apoptosis, because all cells of the conjunctiva, even if dysplastic, may be well oxygenated [ 13 ].…”

“…Formalin fixation and paraffin embedding of pterygium and healthy conjunctiva specimens were performed immediately after surgery according to our routine protocols, as previously described [ 13 ]. Briefly, specimens were fixed in 4% formalin for 12 h, dehydrated in alcohol, and finally processed for paraffin embedding.…”