Sinha Snigdha, Das Subhashish, Mohiyuddin S M Azeem
Pathology, Sri Devaraj Urs Medical College, Kolar, IND.
Otorhinolaryngology and Head and Neck Surgery, Sri Devaraj Urs Medical College, Kolar, IND.
Cureus. 2023 Feb 27;15(2):e35526. doi: 10.7759/cureus.35526. eCollection 2023 Feb.
Background Head and neck cancers are highly aggressive, frequently occurring cancers that are prevalent worldwide. The mainstay of their treatment is surgery, followed by adjuvant therapy. Various studies have documented the usefulness of molecular markers in carcinogenesis and have proven helpful in the diagnosis and treatment of head and neck cancers. Cyclin D1 is a proto‑oncogene, overexpression of which leads to the accelerated entry of cells in the S phase of the cell cycle, causing uncontrolled proliferation of the cells. The dysregulation of human epidermal growth factor receptor 2 (HER2) neu is also related to multiple features of malignancy, including loss of cell cycle control, induction of angiogenesis, and resistance to apoptotic stimuli. This study seeks to identify a subset of patients with a bad prognosis who may require aggressive treatment strategies. Aim This study aims to determine the proportion of the expression of cyclin D1 and HER2 neu in head and neck squamous cell carcinoma (HNSCC) and analyze the association between the expression of cyclin D1 and HER2 neu using histological grading, tumor, node, and metastasis (TNM) staging, and nodal status of the tumor. Furthermore, this study also aims to document clinical outcomes, such as locoregional control, depth of invasion (DOI), and regional metastasis regarding the expression of cyclin D1 and HER2 neu in HNSCC. Setting and design This study is a laboratory-based observational study. Materials and methods Seventy histologically proven cases of HNSCC were studied for various histopathological parameters, and further immunohistochemistry (IHC) was performed for cyclin D1 and HER2 neu. The expression and intensity of cyclin D1 were multiplied, and the total score was derived. The College of American Pathologists/American Society of Clinical Oncology (CAP/ASCO) guidelines for HER2 neu testing in breast cancer were used for scoring. Result Out of 70 cases, 52 (75%) demonstrated strong and moderate positivity for cyclin D1, and the p-values were 0.017, 0.001, and 0.032 for depth of invasion, TNM stage, and lymph node metastases, respectively, for cyclin D1, which was considered statistically significant. For HER2 neu, five out of 70 cases were positive, and the p-value was significant for depth of invasion (0.008). Conclusion The expression of the above marker cyclin D1 increases with stage, DOI, and positive lymph node status. Hence, cyclin D1 immunoexpression can be helpful in the early assessment of HNSCC behavior and can serve as an independent prognostic marker. Furthermore, it was observed that HER2 neu was significant with an increase in depth of invasion of tumor, which, in the American Joint Committee on Cancer (AJCC) eighth edition, is considered an important factor for determining the stage of the tumor. Further research is needed to examine whether HER2 neu can act as a prognostic factor for HNSCC and if it can be targeted for treatment options.
头颈癌是侵袭性很强、全球常见的频发癌症。其主要治疗方法是手术,随后进行辅助治疗。多项研究记录了分子标志物在致癌过程中的作用,并已证明其对头颈癌的诊断和治疗有帮助。细胞周期蛋白D1是一种原癌基因,其过度表达会导致细胞加速进入细胞周期的S期,导致细胞不受控制地增殖。人表皮生长因子受体2(HER2)neu的失调也与恶性肿瘤的多种特征有关,包括细胞周期控制丧失、血管生成诱导和对凋亡刺激的抗性。本研究旨在识别可能需要积极治疗策略的预后不良患者亚组。
本研究旨在确定头颈鳞状细胞癌(HNSCC)中细胞周期蛋白D1和HER2 neu的表达比例,并使用组织学分级、肿瘤、淋巴结和转移(TNM)分期以及肿瘤的淋巴结状态分析细胞周期蛋白D1和HER2 neu表达之间的关联。此外,本研究还旨在记录HNSCC中细胞周期蛋白D1和HER2 neu表达的临床结果,如局部区域控制、浸润深度(DOI)和区域转移。
本研究是一项基于实验室的观察性研究。
对70例经组织学证实的HNSCC病例进行各种组织病理学参数研究,并对细胞周期蛋白D1和HER2 neu进行进一步的免疫组织化学(IHC)检测。将细胞周期蛋白D1的表达和强度相乘,得出总分。采用美国病理学家学会/美国临床肿瘤学会(CAP/ASCO)乳腺癌HER2 neu检测指南进行评分。
在70例病例中,52例(75%)细胞周期蛋白D1呈强阳性和中度阳性,细胞周期蛋白D1的浸润深度、TNM分期和淋巴结转移的p值分别为0.017、0.001和0.032(被认为具有统计学意义)。对于HER2 neu,70例中有5例呈阳性,浸润深度的p值具有统计学意义(0.008)。
上述标志物细胞周期蛋白D1的表达随分期、DOI和阳性淋巴结状态增加。因此,细胞周期蛋白D1免疫表达有助于早期评估HNSCC行为,并可作为独立的预后标志物。此外,观察到HER2 neu与肿瘤浸润深度增加具有相关性,在美国癌症联合委员会(AJCC)第八版中,这被认为是确定肿瘤分期的一个重要因素。需要进一步研究以检查HER2 neu是否可作为HNSCC的预后因素以及是否可作为治疗靶点。