Fig 2: (A) shows hematoxylin-eosin (H&E) stained tissue specimens of the three subjects for each condition (×200). (B) shows glucocorticoid-induced leucine zipper (GILZ)-positive nuclear staining in benign keratosis as well as mild-moderate dysplasia and severe dysplasia throughout the full thickness of the epithelium, while GILZ-positive nuclear staining is observed throughout malignant epithelial cells (×200).

Fig 3: Glucocorticoids and Cancer. Exogenous administration of GCs and the production of GCs by adrenal glands cause an elevation in blood levels with consequent effects on tumors. The potent pro-apoptotic effects of GCs mediated in part via the modulation of the Bcl2 family of proteins as well as their immunomodulatory effects on Th cells and Tregs contribute to their beneficial effects in lymphohematopoietic malignancies. On the other hand, the use of GCs as adjuvant therapy in solid tumors can exert various effects on tumor growth and metastasis via a myriad of mechanisms, several of which are summarized in the diagram [2–6]. Importantly, more recent information suggests the presence of a non-adrenal GC system in several tissues including the oral mucosa. Accordingly, cortisol generation and its deactivation to cortisone occurs via tissue-specific 11-ß-HSD1 and 2, respectively. The reduced expression of 11-ß-HSD2 in oral SCC likely raises tissue cortisol level, resulting in glucocorticoid receptor-mediated effects. Consequently, it is proposed that the upregulation of pro-survival pathways coupled with impaired immune surveillance results in increased tumor size, reduced susceptibility to cytotoxic agents, and increased propensity for metastasis [10, 11]. Importantly, GCs are potent inducers of glucocorticoid-induced leucine zipper (GILZ) and serum-glucocorticoid-regulated kinase-1 (SGK-1) expressions, which are implicated in the pathogenesis of various tumors as described in the text; however, their status in potentially malignant or malignant oral lesions is not known and is the subject of this study. Abbreviations: 11-ß-HSD, 11-ß-hydroxysteroid dehydrogenase; GCs, glucocorticoids; MAPK, mitogen-activated protein kinase; SCC, squamous cell carcinoma; Th, T-helper cells; Tregs, regulatory T cells; VEGF, vascular endothelial growth factor.

Fig 4: Panels show GILZ and Annexin A1 staining for one tissue sample from control, oral candidiasis, and oral lichen planus groups at higher magnification to better illustrate staining patterns. While GILZ immunostaining is confined to nuclei, Annexin A1 immunostaining is seen for nuclei, cytoplasm, and cell membrane. Further, sparring of Annexin A1 immunostaining is seen for basal layers of epithelium, although less discernable for OLP but more prominent for OC, compared to control, specimens. Scale bar: 50 µm.

Fig 5: Representative images are shown for (A) hematoxylin-eosin, (B) GILZ, (C) SGK-1, and (D) pSGK-1 (D) for one case of severe epithelial dysplasia ×400.