Immunohistochemical quantification of partial-EMT in oral cavity squamous cell carcinoma primary tumors is associated with nodal metastasis. (December 2019)

• Record Type: Journal Article
• Authors: Parikh, Anuraag S.; Puram, Sidharth V.; Faquin, William C.; Richmon, Jeremy D.; Emerick, Kevin S.; Deschler, Daniel G.; Varvares, Mark A.; Tirosh, Itay; Bernstein, Bradley E.; Lin, Derrick T.
• Is Part Of: Oral oncology. Volume 99(2019)
• Publication Date: 2019-12
• Subjects: Head and neck squamous cell carcinoma -- Oral cavity -- Epithelial-mesenchymal transition -- Lymph node -- Metastasis -- Immunohistochemistry; Mouth -- Cancer -- Periodicals; Mouth -- Tumors -- Periodicals; Mouth Diseases -- Periodicals; Mouth Neoplasms -- Periodicals; Bouche -- Cancer -- Périodiques; Bouche -- Tumeurs -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9943105
• DOI: 10.1016/j.oraloncology.2019.104458
• Languages: English
• ISSNs: 1368-8375

Abstract

Highlights: Tissue microarrays were created from 99 oral cavity carcinoma patients. Immunohistochemical quantification of partial-EMT was performed using 4 markers. P-EMT was associated with nodal metastasis, including occult nodal disease. P-EMT was also associated with perineural invasion and high grade. Abstract: Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.