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

doi:10.1016/j.oraloncology.2019.104458

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

Department of Molecular Cell Biology

Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-review

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 NO neck and/or for adjuvant therapy planning.

Original language	English
Article number	104458
Number of pages	6
Journal	Oral Oncology
Volume	99
Early online date	6 Nov 2019
DOIs	https://doi.org/10.1016/j.oraloncology.2019.104458
State	Published - Dec 2019
Event	Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery-Foundation (AAO-HNSF) and OTO Experience - Atlanta, Gabon Duration: 7 Oct 2018 → 10 Oct 2018

All Science Journal Classification (ASJC) codes

Oral Surgery
Oncology
Cancer Research

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10.1016/j.oraloncology.2019.104458

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Parikh, A. S., Puram, S. V., Faquin, W. C., Richmon, J. D., Emerick, K. S., Deschler, D. G., Varvares, M. A., Tirosh, I., Bernstein, B. E., & Lin, D. T. (2019). Immunohistochemical quantification of partial-EMT in oral cavity squamous cell carcinoma primary tumors is associated with nodal metastasis. Oral Oncology, 99, Article 104458. https://doi.org/10.1016/j.oraloncology.2019.104458

@article{2fe82ed27c60478482250d8eea274ab9,

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

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 NO neck and/or for adjuvant therapy planning.",

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

note = "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.; Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery-Foundation (AAO-HNSF) and OTO Experience ; Conference date: 07-10-2018 Through 10-10-2018",

year = "2019",

month = dec,

doi = "10.1016/j.oraloncology.2019.104458",

language = "الإنجليزيّة",

volume = "99",

journal = "Oral Oncology",

issn = "1368-8375",

publisher = "Elsevier Ltd.",

}

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 - 10.1016/j.oraloncology.2019.104458

DO - 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 -

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

Abstract

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