TY - JOUR
T1 - Immunohistochemical quantification of partial-EMT in oral cavity squamous cell carcinoma primary tumors is associated with nodal metastasis
AU - Parikh, Anuraag S.
AU - Puram, Sidharth V.
AU - Faquin, William C.
AU - Richmon, Jeremy D.
AU - Emerick, Kevin S.
AU - Deschler, Daniel G.
AU - Varvares, Mark A.
AU - Tirosh, Itay
AU - Bernstein, Bradley E.
AU - Lin, Derrick T.
N1 - Funding - Broadnext10 Catalytic Steps Translation Research Grant, #4300002, 2016, Broad Institute, Cambridge, MA (PI: Anuraag Parikh, MD and Sidharth Puram, MD PhD). Funds from the National Cancer Institute and NIH common fund (PI: Bradley Bernstein, MD PhD) were also used. The funding sources had no involvement in the design, conduct, and reporting of the research. Presented as podium presentation at: American Academy of Otolaryngology-Head and Neck Surgery Annual Meeting, 2018 Oct 7–10, Atlanta, GA.
PY - 2019/12
Y1 - 2019/12
N2 - 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 NO neck and/or for adjuvant therapy planning.
AB - 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 NO neck and/or for adjuvant therapy planning.
UR - http://www.scopus.com/inward/record.url?scp=85074337125&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.oraloncology.2019.104458
DO - https://doi.org/10.1016/j.oraloncology.2019.104458
M3 - مقالة
SN - 1368-8375
VL - 99
JO - Oral Oncology
JF - Oral Oncology
M1 - 104458
T2 - Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery-Foundation (AAO-HNSF) and OTO Experience
Y2 - 7 October 2018 through 10 October 2018
ER -