Department of Otolaryngology - Head & Neck Surgery, University of Missouri, Columbia, MO, United States.
Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, United States.
Oral Oncol. 2022 Sep;132:106002. doi: 10.1016/j.oraloncology.2022.106002. Epub 2022 Jun 29.
The mechanisms of perineural invasion (PNI) in oral cavity squamous cell carcinoma are only partially understood, and no studies have specifically investigated the role of perineural fibroblasts in PNI. Here, we identified fibroblasts within the microenvironment of perineural invasion and assessed their expression of matrix metalloproteinase-2 (MMP-2).
Tumor specimens from 12 patients with oral cavity squamous cell carcinoma and pathologically-confirmed perineural invasion were stained by immunohistochemistry (IHC) for vimentin (positive control) and MMP-2. Scoring was quantified and compared at nerves involved with PNI and nerves uninvolved with PNI.
All 12 patients had perineural fibroblasts around involved and uninvolved nerves as marked by vimentin IHC staining. Perineural fibroblasts had detectable MMP-2 expression at areas of perineural invasion in all 12 patients, but no patients had MMP-2 expression by fibroblasts at nerves without PNI.
MMP-2 is expressed by fibroblasts within the microenvironment of perineural invasion, and MMP-2 expression by fibroblasts is a possible mechanism of perineural invasion by oral cavity squamous cell carcinoma. MMP-2 may be an anti-cancer target among oral cavity squamous cell carcinoma patients with PNI.
口腔鳞状细胞癌发生神经周围侵犯（PNI）的机制尚不完全清楚，目前尚无研究专门探讨周围神经纤维中的成纤维细胞在 PNI 中的作用。本研究旨在确定 PNI 微环境中的成纤维细胞，并评估其基质金属蛋白酶-2（MMP-2）的表达情况。
对 12 例经病理证实存在 PNI 的口腔鳞状细胞癌患者的肿瘤标本进行免疫组化染色（IHC），以检测波形蛋白（阳性对照）和 MMP-2 的表达。对 PNI 累及神经和未累及神经的 MMP-2 表达进行评分和比较。
12 例患者的受累和未受累神经周围均可见到波形蛋白 IHC 染色阳性的周围神经成纤维细胞。12 例患者的所有 PNI 区域均可见到周围神经成纤维细胞表达 MMP-2，但在无 PNI 的神经中，无患者的成纤维细胞表达 MMP-2。
MMP-2 由 PNI 微环境中的成纤维细胞表达，成纤维细胞表达 MMP-2 可能是口腔鳞状细胞癌发生 PNI 的机制之一。MMP-2 可能是存在 PNI 的口腔鳞状细胞癌患者的一个潜在的抗癌治疗靶点。
