Rahrotaban Sedigheh, Mahdavi Nazanin, Abdollahi Alireza, Yazdani Farzad, Kaghazloo Ali, Derakhshan Samira
Departments of Oral and Maxillofacial Pathology, School of Dentistry.
Pathology, Imam Hospital Complex, Cancer institute.
Appl Immunohistochem Mol Morphol. 2019 Oct;27(9):683-688. doi: 10.1097/PAI.0000000000000687.
The important role of the human papillomavirus (HPV) is widely established in oropharyngeal squamous cell carcinoma (OPSCC). The behavior of a OPSCCs especially induced by HPV might be influenced by the tissue microenvironment and its changes according to the tumor nature. Recognition of the role of the tumor microenvironment on the behavior of neoplastic cells has led to utilization of the microenvironment to use as therapeutic target. Carcinoma-associated fibroblasts (CAFs), the most abundant cells in the tumor microenvironment, show wide-spread expression of alpha-smooth muscle actin (α-SMA). We focused on CAFs, its presence in OPSCC and the relationship with HPV for the first time. Expression of α-SMA protein in CAFs of the tumor microenvironment of the 44 formalin-fixed paraffin-embedded tissue blocks from the primary tumor of OPSCC evaluated by immunohistochemistry between HPV-positive and HPV-negative tumors separated by nested polymerase chain reaction. In 44 samples 23 HPV-positive cases were detected. Statistically there were significant differences between histopathologic grade, percent and final score of α-SMA and HPV expression. Significant difference between HPV expression and inflammation, intensity, and clinical parameters was not identified in the present study. Our results indicate that CAFs are a common finding in the microenvironment of HPV-positive OPSCC and associated with higher histopathologic grade. Therapeutic strategies to use CAF-mediated drugs need to be considered and evaluated more for treatment of HPV-positive OPSCC.
人乳头瘤病毒（HPV）在口咽鳞状细胞癌（OPSCC）中的重要作用已得到广泛证实。OPSCC的行为，尤其是由HPV诱导的OPSCC行为，可能会受到组织微环境及其根据肿瘤性质所发生变化的影响。认识到肿瘤微环境对肿瘤细胞行为的作用，促使人们将微环境用作治疗靶点。癌相关成纤维细胞（CAF）是肿瘤微环境中最丰富的细胞，广泛表达α平滑肌肌动蛋白（α-SMA）。我们首次关注CAF、其在OPSCC中的存在情况以及与HPV的关系。通过免疫组织化学评估44个来自OPSCC原发肿瘤的福尔马林固定石蜡包埋组织块的肿瘤微环境中CAF内α-SMA蛋白的表达情况，这些样本通过巢式聚合酶链反应区分HPV阳性和HPV阴性肿瘤。在44个样本中检测到23例HPV阳性病例。在组织病理学分级、α-SMA的百分比和最终评分与HPV表达之间存在统计学上的显著差异。在本研究中未发现HPV表达与炎症、强度及临床参数之间存在显著差异。我们的结果表明，CAF在HPV阳性OPSCC的微环境中很常见，且与更高的组织病理学分级相关。对于HPV阳性OPSCC的治疗，需要更多地考虑和评估使用CAF介导药物的治疗策略。
