Mozaffari Mahmood S, Abdelsayed Rafik, Emami Sahar, Kavuri Sravan
Department of Oral Biology and Diagnostic Sciences, The Dental College of Georgia, Augusta University, Augusta, GA, United States.
Department of Pathology, Medical College of Georgia, Augusta University, Augusta, GA, United States.
Front Oral Health. 2023 Oct 25;4:1285139. doi: 10.3389/froh.2023.1285139. eCollection 2023.
Human papillomavirus virus-related oropharyngeal squamous cell carcinoma (HPV-OPSCC) comprises a significant portion of head and neck cancers. Several glucocorticoid-inducible proteins play important roles in pathogenesis of some cancers but their status and roles in HPV-OPSCC remain elusive; these include the glucocorticoid-induced leucine zipper (GILZ), Annexin-A1 and serum glucocorticoid-regulated kinase-1 (SGK-1).
We determined expression profiles of these proteins, using immunohistochemistry, in archived biopsy samples of patients diagnosed with HPV-OPSCC; samples of non-cancer oral lesions (e.g., hyperkeratosis) were used as controls.
GILZ staining was primarily confined to nuclei of all tissues but, in HPV-OPSCC specimens, neoplastic cells exhibiting mitosis displayed prominent cytoplasmic GILZ expression. On the other hand, nuclear, cytoplasmic and membranous Annexin-A1 staining was observed in suprabasal cell layers of control specimens. A noted feature of the HPV-OPSCC specimens was few clusters of matured and differentiated nonbasaloid cells that showed prominent nuclear and cytoplasmic Annexin-A1 staining while the remainder of the tumor mass was devoid of staining. Cytoplasmic and nuclear staining for SGK-1 was prominent for control than PV-OPSCC specimens while staining for phosphorylated SGK-1 (pSGK-1; active) was prominent for cell membrane and cytoplasm of control specimens but HPV-OPSCC specimens showed mild and patchy nuclear and cytoplasmic staining. Semi-quantitative analysis of GILZ immunostaining indicated increased staining area but similar normalized staining for HPV-OPSCC compared to control specimens. By contrast, staining area and normalized staining were reduced for other proteins in HPV-OPSCC than control specimens.
Our collective observations suggest differential cellular localization and expression of glucocorticoid-inducible proteins in HPV-OPSCC suggestive of different functional roles in pathogenesis of this condition.
人乳头瘤病毒相关的口咽鳞状细胞癌（HPV-OPSCC）占头颈癌的很大一部分。几种糖皮质激素诱导蛋白在某些癌症的发病机制中起重要作用，但它们在HPV-OPSCC中的状态和作用仍不清楚；这些蛋白包括糖皮质激素诱导亮氨酸拉链（GILZ）、膜联蛋白A1和血清糖皮质激素调节激酶-1（SGK-1）。
我们采用免疫组织化学方法，在确诊为HPV-OPSCC的患者存档活检样本中测定这些蛋白的表达谱；以非癌性口腔病变（如角化过度）样本作为对照。
GILZ染色主要局限于所有组织的细胞核，但在HPV-OPSCC标本中，出现有丝分裂的肿瘤细胞显示出明显的细胞质GILZ表达。另一方面，在对照标本的基底上层细胞层中观察到细胞核、细胞质和细胞膜的膜联蛋白A1染色。HPV-OPSCC标本的一个显著特征是少数成熟和分化的非基底样细胞簇显示出明显的细胞核和细胞质膜联蛋白A1染色，而肿瘤块的其余部分则无染色。SGK-1的细胞质和细胞核染色在对照标本中比HPV-OPSCC标本更明显，而磷酸化SGK-1（pSGK-1；活性形式）的染色在对照标本的细胞膜和细胞质中明显，但HPV-OPSCC标本显示出轻度和散在的细胞核和细胞质染色。GILZ免疫染色的半定量分析表明，与对照标本相比，HPV-OPSCC的染色面积增加，但标准化染色相似。相比之下，HPV-OPSCC中其他蛋白的染色面积和标准化染色比对照标本减少。
我们的总体观察结果表明，糖皮质激素诱导蛋白在HPV-OPSCC中的细胞定位和表达存在差异，提示其在该病发病机制中具有不同的功能作用。
