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 journal › Article › peer-review
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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 -