YMT Dental College and Research Institute, Navi Mumbai, Maharashtra, India.
Head Neck Pathol. 2022 Jun;16(2):453-465. doi: 10.1007/s12105-021-01384-8. Epub 2021 Oct 16.
Tumour heterogeneity in oral cancer is attributed to the presence of cancer stem cells (CSCs). CSCs are the most migratory and metastatic cellular subpopulation within tumours. Assessment of CSC markers as significant predictors of lymph node metastasis may prove valuable in the clinical setting. Furthermore, analysis of this panel of putative stem cell markers in oral dysplasia may additionally inform of the likelihood for oral potentially malignant disorders (OPMDs) to progress to oral squamous cell carcinoma (OSCC). The present study aims to assess the significance of CSC markers in the progression of OPMDs to OSCC and assessment of lymph node metastasis in OSCC. CD44 and ALDH1 were assessed immunohistochemically in 25 normal, 30 OPMDs, and 24 OSCCs. CD44 is a membranous marker and ALDH1 is a cytoplasmic marker. The immunohistochemical expression of these markers were compared between OPMDs with and without dysplasia, as well as between low-risk and high-risk dysplasias. Similarly, expression was compared between OSCC with and without lymph node metastasis and among grades of OSCC. Positive CD44 expression was seen in all normal mucosal tissues. The expression decreased from normal epithelium to OPMDs but increased in OSCC. CD44 expression was positive in 21 cases of OSCC (87.5%) and reduced from well-differentiated to poorly differentiated OSCC. CD44 staining index was higher in OSCC without lymph node metastasis (3.59) when compared with OSCC with lymph node metastasis (1.33). There was a statistically significant difference observed in the ALDH1 staining index among three groups (p < 0.05), with highest expression seen in OSCC. Within OPMDs, the ALDH1 staining index was statistically higher in OPMDs with dysplasia as compared to OPMDs without dysplasia. Furthermore, the expression was higher in OPMDs with high-risk dysplasia when compared with low-risk dysplasia, but this was not statistically significant (p = 0.82). In conclusion, The CD44 positive population possesses properties of CSCs in head and neck carcinoma, and continuous shedding could be found after CD44 down-regulation. The present study reports differences in ALDH1 expression between OPMDs with and without dysplasia, dysplastic and non-dysplastic epithelia, and low-risk and high-risk dysplasia. These findings may suggest ALDH1 as a specific marker for dysplasia. CD44 demonstrated a difference in staining index in OSCC without lymph node metastasis versus OSCC with lymph node metastasis. These findings may suggest CD44 as a marker for lymph node metastasis. Both proteins may play key roles in the tumorigenicity of CSCs in OPMDs and OSCC.
口腔癌中的肿瘤异质性归因于癌症干细胞 (CSC) 的存在。CSC 是肿瘤中最具迁移性和转移性的细胞亚群。评估 CSC 标志物作为淋巴结转移的显著预测因子，在临床环境中可能具有重要意义。此外，在口腔发育不良中分析这个潜在的干细胞标志物面板，还可以提供口腔潜在恶性疾病 (OPMD) 进展为口腔鳞状细胞癌 (OSCC) 的可能性。本研究旨在评估 CSC 标志物在 OPMD 进展为 OSCC 以及评估 OSCC 中淋巴结转移中的意义。使用免疫组织化学方法在 25 例正常组织、30 例 OPMD 和 24 例 OSCC 中评估 CD44 和 ALDH1。CD44 是一种膜标记物，ALDH1 是一种细胞质标记物。比较了 OPMD 有无发育不良以及低风险和高风险发育不良之间这些标记物的免疫组织化学表达。同样，比较了有和无淋巴结转移的 OSCC 之间以及 OSCC 分级之间的表达。所有正常黏膜组织均可见 CD44 阳性表达。表达从正常上皮减少到 OPMD，但在 OSCC 中增加。21 例 OSCC（87.5%）中 CD44 表达阳性，从分化良好的 OSCC 到分化不良的 OSCC 减少。与有淋巴结转移的 OSCC（1.33）相比，无淋巴结转移的 OSCC（3.59）的 CD44 染色指数更高。三组之间的 ALDH1 染色指数存在统计学差异（p<0.05），OSCC 中表达最高。在 OPMD 中，与无发育不良的 OPMD 相比，有发育不良的 OPMD 的 ALDH1 染色指数更高。此外，高风险发育不良的 OPMD 表达高于低风险发育不良，但无统计学意义（p=0.82）。总之，CD44 阳性人群在头颈部癌中具有 CSC 的特性，并且在 CD44 下调后可能会发现连续脱落。本研究报告了 OPMD 有无发育不良、发育不良和非发育不良上皮以及低风险和高风险发育不良之间 ALDH1 表达的差异。这些发现可能表明 ALDH1 是发育不良的特异性标志物。CD44 在无淋巴结转移的 OSCC 与有淋巴结转移的 OSCC 之间的染色指数存在差异。这些发现可能表明 CD44 是淋巴结转移的标志物。这两种蛋白在 OPMD 和 OSCC 中 CSC 的肿瘤发生中可能发挥关键作用。
