Immunohistochemical quantification of partial-EMT in oral cavity squamous cell carcinoma primary tumors is associated with nodal metastasis

Anuraag S. Parikh, Sidharth V. Puram, William C. Faquin, Jeremy D. Richmon, Kevin S. Emerick, Daniel G. Deschler, Mark A. Varvares, Itay Tirosh, Bradley E. Bernstein, Derrick T. Lin

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4 Scopus citations

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.

Original languageEnglish
Article number104458
JournalOral Oncology
Volume99
DOIs
StatePublished - Dec 2019

Keywords

  • Epithelial-mesenchymal transition
  • Head and neck squamous cell carcinoma
  • Immunohistochemistry
  • Lymph node
  • Metastasis
  • Oral cavity

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