Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, MA, USA; Department of Otolaryngology, Harvard Medical School, Boston, MA, USA.
Department of Otolaryngology-Head and Neck Surgery and Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
Oral Oncol. 2019 Dec;99:104458. doi: 10.1016/j.oraloncology.2019.104458. Epub 2019 Nov 6.
Quantify by immunohistochemistry (IHC) a partial epithelial-to-mesenchymal transition (p-EMT) population in oral cavity squamous cell carcinoma (OCSCC) and determine its predictive value for lymph node metastasis.
Tissue microarrays (TMA) were created using 2 mm cores from 99 OCSCC patients (47 with low volume T2 disease, 52 with high volume T4 disease, and ∼50% in each group with nodal metastasis). IHC staining was performed for three validated p-EMT markers (PDPN, LAMB3, LAMC2) and one marker of well-differentiated epithelial cells (SPRR1B). Staining was quantified in a blinded manner by two reviewers. Tumors were classified as malignant basal subtype based on staining for the four markers. In this subset, the p-EMT score was computed as the average of p-EMT markers.
84 tumors were classified as malignant basal. There was 87% inter-rater consistency in marker quantification. There were associations of p-EMT scores with higher grade (2.15 vs. 1.92, p = 0.04), PNI (2.13 vs. 1.83, p = 0.003), and node positivity (2.09 vs. 1.87, p = 0.02), including occult node positivity (56% vs. 19%, p = 0.005). P-EMT was independently associated with nodal metastasis in a multivariate analysis (OR 3.12, p = 0.039). Overall and disease free survival showed trends towards being diminished in the p-EMT high group.
IHC quantification of p-EMT in OCSCC primary tumors is reliably associated with nodal metastasis, PNI, and high grade. With prospective validation, p-EMT biomarkers may aid in decision-making over whether to perform a neck dissection in the N0 neck and/or for adjuvant therapy planning.
通过免疫组织化学（IHC）量化口腔鳞状细胞癌（OCSCC）中的部分上皮-间充质转化（p-EMT）人群，并确定其对淋巴结转移的预测价值。
使用 99 例 OCSCC 患者的 2mm 核心组织创建组织微阵列（TMA）（47 例为低体积 T2 疾病，52 例为高体积 T4 疾病，每组约有 50%的患者有淋巴结转移）。对三种经过验证的 p-EMT 标志物（PDPN、LAMB3、LAMC2）和一种分化良好的上皮细胞标志物（SPRR1B）进行 IHC 染色。两名评审员以盲法方式对染色进行定量。根据四种标志物的染色，将肿瘤分类为恶性基底亚型。在此亚组中，p-EMT 评分计算为 p-EMT 标志物的平均值。
84 例肿瘤被归类为恶性基底。标志物定量的两位评审者之间有 87%的一致性。p-EMT 评分与更高的分级（2.15 与 1.92，p=0.04）、PNI（2.13 与 1.83，p=0.003）和淋巴结阳性（2.09 与 1.87，p=0.02）相关，包括隐匿性淋巴结阳性（56%与 19%，p=0.005）。在多变量分析中，p-EMT 与淋巴结转移独立相关（OR 3.12，p=0.039）。总体和无病生存在 p-EMT 高组中呈下降趋势。
在 OCSCC 原发肿瘤中，p-EMT 的 IHC 定量可靠地与淋巴结转移、PNI 和高级别相关。通过前瞻性验证，p-EMT 生物标志物可能有助于决策是否对 N0 颈部进行颈部清扫术，以及是否进行辅助治疗计划。
