IGF-1R expression is associated with HPV-negative status and adverse survival in head and neck squamous cell cancer
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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Oxford University Press
2015
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| _version_ | 1824458592397295616 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Dale, OT |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2025-02-19T04:28:20Z |
| format | Journal article |
| id | oxford-uuid:6eb0a5cf-78db-46ca-af8d-f309924de3d4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2025-02-19T04:28:20Z |
| publishDate | 2015 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:6eb0a5cf-78db-46ca-af8d-f309924de3d42024-12-11T10:15:23ZIGF-1R expression is associated with HPV-negative status and adverse survival in head and neck squamous cell cancerJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6eb0a5cf-78db-46ca-af8d-f309924de3d4EnglishSymplectic Elements at OxfordOxford University Press2015Dale, OTAleksic, TShah, KAHan, CMehanna, HRapozo, DCMSheard, JDHGoodyear, PUpile, NSRobinson, MJones, TMWinter, SMacaulay, VMHead 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. |
| spellingShingle | 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 IGF-1R expression is associated with HPV-negative status and adverse survival in head and neck squamous cell cancer |
| title | IGF-1R expression is associated with HPV-negative status and adverse survival in head and neck squamous cell cancer |
| title_full | IGF-1R expression is associated with HPV-negative status and adverse survival in head and neck squamous cell cancer |
| title_fullStr | IGF-1R expression is associated with HPV-negative status and adverse survival in head and neck squamous cell cancer |
| title_full_unstemmed | IGF-1R expression is associated with HPV-negative status and adverse survival in head and neck squamous cell cancer |
| title_short | IGF-1R expression is associated with HPV-negative status and adverse survival in head and neck squamous cell cancer |
| title_sort | igf 1r expression is associated with hpv negative status and adverse survival in head and neck squamous cell cancer |
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