IGF-1R expression is associated with HPV-negative status and adverse survival in head and neck squamous cell cancer

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IGF-1R expression is associated with HPV-negative status and adverse survival in head and neck squamous cell cancer. / Dale, Oliver T; Aleksic, Tamara; Shah, Ketan A; Han, Cheng; Mehanna, Hisham; Rapozo, Davy C M; Sheard, Jon D H; Goodyear, Paul; Upile, Navdeep S; Robinson, Max; Jones, Terence M; Winter, Stuart; Macaulay, Valentine M.

In: Carcinogenesis, Vol. 36, No. 6, 06.2015, p. 648-55.

Research output: Contribution to journalArticle

Harvard

Dale, OT, Aleksic, T, Shah, KA, Han, C, Mehanna, H, Rapozo, DCM, Sheard, JDH, Goodyear, P, Upile, NS, Robinson, M, Jones, TM, Winter, S & Macaulay, VM 2015, 'IGF-1R expression is associated with HPV-negative status and adverse survival in head and neck squamous cell cancer', Carcinogenesis, vol. 36, no. 6, pp. 648-55. https://doi.org/10.1093/carcin/bgv053

APA

Dale, O. T., Aleksic, T., Shah, K. A., Han, C., Mehanna, H., Rapozo, D. C. M., Sheard, J. D. H., Goodyear, P., Upile, N. S., Robinson, M., Jones, T. M., Winter, S., & Macaulay, V. M. (2015). IGF-1R expression is associated with HPV-negative status and adverse survival in head and neck squamous cell cancer. Carcinogenesis, 36(6), 648-55. https://doi.org/10.1093/carcin/bgv053

Vancouver

Author

Dale, Oliver T ; Aleksic, Tamara ; Shah, Ketan A ; Han, Cheng ; Mehanna, Hisham ; Rapozo, Davy C M ; Sheard, Jon D H ; Goodyear, Paul ; Upile, Navdeep S ; Robinson, Max ; Jones, Terence M ; Winter, Stuart ; Macaulay, Valentine M. / IGF-1R expression is associated with HPV-negative status and adverse survival in head and neck squamous cell cancer. In: Carcinogenesis. 2015 ; Vol. 36, No. 6. pp. 648-55.

Bibtex

@article{0ae642c4fa7442bb8e14b7c69a13543d,
title = "IGF-1R expression is associated with HPV-negative status and adverse survival in head and neck squamous cell cancer",
abstract = "Head and neck squamous cell carcinomas (HNSCC) are treated with surgery, radiotherapy and cisplatin-based chemotherapy, but survival from locally-advanced disease remains poor, particularly in patients whose tumors are negative for Human papillomavirus (HPV). Type 1 IGF receptor (IGF-1R) is known to promote tumorigenesis and resistance to cancer therapeutics. Here, we assessed IGF-1R immunohistochemistry on tissue microarrays containing 852 cores from 346 HNSCC patients with primary tumors in the oropharynx (n = 231), larynx (85), hypopharynx (28), oral cavity (2). Of these, 236 (68%) were HPV-negative, 110 (32%) positive. IGF-1R was detected in the cell membrane of 36% and cytoplasm of 92% of HNSCCs; in 64 cases with matched normal tonsillar epithelium, IGF-1R was overexpressed in the HNSCCs (P < 0.001). Overall survival (OS) and disease-specific survival (DSS) were reduced in patients whose tumors contained high membrane IGF-1R [OS: hazard ratio (HR) = 1.63, P = 0.006; DSS: HR = 1.63, P = 0.016], cytoplasmic IGF-1R (OS: HR = 1.58, P = 0.009; DSS: HR = 1.58, P = 0.024) and total IGF-1R (OS: HR = 2.02, P < 0.001; DSS: HR = 2.2, P < 0.001). High tumor IGF-1R showed significant association with high-tumor T-stage (P < 0.001) and HPV-negativity (P < 0.001), and was associated with shorter OS when considering patients with HPV-positive (P = 0.01) and negative (P = 0.006) tumors separately. IGF-1R was independently associated with survival in multivariate analysis including HPV, but not when lymphovascular invasion, perineural spread and T-stage were included. Of these factors, only IGF-1R can be manipulated; the association of IGF-1R with aggressive disease supports experimental incorporation of anti-IGF-1R agents into multimodality treatment programs for HPV-negative and high IGF-1R HPV-positive HNSCC.",
keywords = "Adult, Aged, Aged, 80 and over, Carcinoma, Squamous Cell, Cell Transformation, Neoplastic, Combined Modality Therapy, Disease-Free Survival, Drug Resistance, Neoplasm, Female, Head and Neck Neoplasms, Humans, Male, Middle Aged, Neoplasm Staging, Papillomaviridae, Papillomavirus Infections, Receptor, IGF Type 1, Young Adult",
author = "Dale, {Oliver T} and Tamara Aleksic and Shah, {Ketan A} and Cheng Han and Hisham Mehanna and Rapozo, {Davy C M} and Sheard, {Jon D H} and Paul Goodyear and Upile, {Navdeep S} and Max Robinson and Jones, {Terence M} and Stuart Winter and Macaulay, {Valentine M}",
note = "{\textcopyright} The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.",
year = "2015",
month = jun,
doi = "10.1093/carcin/bgv053",
language = "English",
volume = "36",
pages = "648--55",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "6",

}

RIS

TY - JOUR

T1 - IGF-1R expression is associated with HPV-negative status and adverse survival in head and neck squamous cell cancer

AU - Dale, Oliver T

AU - Aleksic, Tamara

AU - Shah, Ketan A

AU - Han, Cheng

AU - Mehanna, Hisham

AU - Rapozo, Davy C M

AU - Sheard, Jon D H

AU - Goodyear, Paul

AU - Upile, Navdeep S

AU - Robinson, Max

AU - Jones, Terence M

AU - Winter, Stuart

AU - Macaulay, Valentine M

N1 - © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PY - 2015/6

Y1 - 2015/6

N2 - Head and neck squamous cell carcinomas (HNSCC) are treated with surgery, radiotherapy and cisplatin-based chemotherapy, but survival from locally-advanced disease remains poor, particularly in patients whose tumors are negative for Human papillomavirus (HPV). Type 1 IGF receptor (IGF-1R) is known to promote tumorigenesis and resistance to cancer therapeutics. Here, we assessed IGF-1R immunohistochemistry on tissue microarrays containing 852 cores from 346 HNSCC patients with primary tumors in the oropharynx (n = 231), larynx (85), hypopharynx (28), oral cavity (2). Of these, 236 (68%) were HPV-negative, 110 (32%) positive. IGF-1R was detected in the cell membrane of 36% and cytoplasm of 92% of HNSCCs; in 64 cases with matched normal tonsillar epithelium, IGF-1R was overexpressed in the HNSCCs (P < 0.001). Overall survival (OS) and disease-specific survival (DSS) were reduced in patients whose tumors contained high membrane IGF-1R [OS: hazard ratio (HR) = 1.63, P = 0.006; DSS: HR = 1.63, P = 0.016], cytoplasmic IGF-1R (OS: HR = 1.58, P = 0.009; DSS: HR = 1.58, P = 0.024) and total IGF-1R (OS: HR = 2.02, P < 0.001; DSS: HR = 2.2, P < 0.001). High tumor IGF-1R showed significant association with high-tumor T-stage (P < 0.001) and HPV-negativity (P < 0.001), and was associated with shorter OS when considering patients with HPV-positive (P = 0.01) and negative (P = 0.006) tumors separately. IGF-1R was independently associated with survival in multivariate analysis including HPV, but not when lymphovascular invasion, perineural spread and T-stage were included. Of these factors, only IGF-1R can be manipulated; the association of IGF-1R with aggressive disease supports experimental incorporation of anti-IGF-1R agents into multimodality treatment programs for HPV-negative and high IGF-1R HPV-positive HNSCC.

AB - Head and neck squamous cell carcinomas (HNSCC) are treated with surgery, radiotherapy and cisplatin-based chemotherapy, but survival from locally-advanced disease remains poor, particularly in patients whose tumors are negative for Human papillomavirus (HPV). Type 1 IGF receptor (IGF-1R) is known to promote tumorigenesis and resistance to cancer therapeutics. Here, we assessed IGF-1R immunohistochemistry on tissue microarrays containing 852 cores from 346 HNSCC patients with primary tumors in the oropharynx (n = 231), larynx (85), hypopharynx (28), oral cavity (2). Of these, 236 (68%) were HPV-negative, 110 (32%) positive. IGF-1R was detected in the cell membrane of 36% and cytoplasm of 92% of HNSCCs; in 64 cases with matched normal tonsillar epithelium, IGF-1R was overexpressed in the HNSCCs (P < 0.001). Overall survival (OS) and disease-specific survival (DSS) were reduced in patients whose tumors contained high membrane IGF-1R [OS: hazard ratio (HR) = 1.63, P = 0.006; DSS: HR = 1.63, P = 0.016], cytoplasmic IGF-1R (OS: HR = 1.58, P = 0.009; DSS: HR = 1.58, P = 0.024) and total IGF-1R (OS: HR = 2.02, P < 0.001; DSS: HR = 2.2, P < 0.001). High tumor IGF-1R showed significant association with high-tumor T-stage (P < 0.001) and HPV-negativity (P < 0.001), and was associated with shorter OS when considering patients with HPV-positive (P = 0.01) and negative (P = 0.006) tumors separately. IGF-1R was independently associated with survival in multivariate analysis including HPV, but not when lymphovascular invasion, perineural spread and T-stage were included. Of these factors, only IGF-1R can be manipulated; the association of IGF-1R with aggressive disease supports experimental incorporation of anti-IGF-1R agents into multimodality treatment programs for HPV-negative and high IGF-1R HPV-positive HNSCC.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Carcinoma, Squamous Cell

KW - Cell Transformation, Neoplastic

KW - Combined Modality Therapy

KW - Disease-Free Survival

KW - Drug Resistance, Neoplasm

KW - Female

KW - Head and Neck Neoplasms

KW - Humans

KW - Male

KW - Middle Aged

KW - Neoplasm Staging

KW - Papillomaviridae

KW - Papillomavirus Infections

KW - Receptor, IGF Type 1

KW - Young Adult

U2 - 10.1093/carcin/bgv053

DO - 10.1093/carcin/bgv053

M3 - Article

C2 - 25896444

VL - 36

SP - 648

EP - 655

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 6

ER -