BACKGROUND: Although heregulin and human epidermal growth factor receptor 3 (HER3) are frequently expressed at high levels in patients with head and neck cancer, their prognostic value remains unclear. The authors explored the prognostic significance of heregulin/HER3 expression in patients with oropharyngeal squamous cell carcinoma (OPSCC), taking into account other HER family members as well as p16 status. METHODS: Ninety-six primary tumor specimens from patients with OPSCC were retrospectively collected and analyzed for heregulin messenger RNA (mRNA) using in situ hybridization and for HER3, epidermal growth factor receptor, and human epidermal growth factor receptor 2 (HER2) using quantitative immunohistochemistry. Heregulin and HER3 mRNA levels were also examined among different tumor types using The Cancer Genome Atlas database. RESULTS: High heregulin mRNA (> the median) correlated significantly with poor overall survival (OS) (hazard ratio [HR], 8.48; 95% confidence interval [95% CI], 2.17-33.17 [P =.002]) but not disease-free survival (HR, 1.52; 95% CI, 0.64-3.65 [P =.341]) in patients with OPSCC. Heregulin mRNA correlated negatively with OS in both patients with p16-positive (P =.049) and p16-negative (P =.091) OPSCC on univariate analysis. High HER3 (> the median) also correlated with poor OS (HR, 4.68; 95% CI, 1.47-14.90 [P =.009]) on multivariate analysis. Epidermal growth factor receptor levels independently correlated with disease-free survival (P =.025) and inversely correlated with p16 status (P =.012). In addition, The Cancer Genome Atlas data demonstrated that head and neck squamous cell carcinoma exhibits higher heregulin expression compared with other solid tumor types examined. CONCLUSIONS: High heregulin mRNA and high HER3 protein levels were found to independently correlate with poor OS in patients with OPSCC. These data support targeting HER3 in patients with heregulin-high OPSCC and warrant further clinical investigation.
BACKGROUND: Although heregulin and human epidermal growth factor receptor 3 (HER3) are frequently expressed at high levels in patients with head and neck cancer, their prognostic value remains unclear. The authors explored the prognostic significance of heregulin/HER3 expression in patients with oropharyngeal squamous cell carcinoma (OPSCC), taking into account other HER family members as well as p16 status. METHODS: Ninety-six primary tumor specimens from patients with OPSCC were retrospectively collected and analyzed for heregulin messenger RNA (mRNA) using in situ hybridization and for HER3, epidermal growth factor receptor, and humanepidermal growth factor receptor 2 (HER2) using quantitative immunohistochemistry. Heregulin and HER3 mRNA levels were also examined among different tumor types using The Cancer Genome Atlas database. RESULTS: High heregulin mRNA (> the median) correlated significantly with poor overall survival (OS) (hazard ratio [HR], 8.48; 95% confidence interval [95% CI], 2.17-33.17 [P =.002]) but not disease-free survival (HR, 1.52; 95% CI, 0.64-3.65 [P =.341]) in patients with OPSCC. Heregulin mRNA correlated negatively with OS in both patients with p16-positive (P =.049) and p16-negative (P =.091) OPSCC on univariate analysis. High HER3 (> the median) also correlated with poor OS (HR, 4.68; 95% CI, 1.47-14.90 [P =.009]) on multivariate analysis. Epidermal growth factor receptor levels independently correlated with disease-free survival (P =.025) and inversely correlated with p16 status (P =.012). In addition, The Cancer Genome Atlas data demonstrated that head and neck squamous cell carcinoma exhibits higher heregulin expression compared with other solid tumor types examined. CONCLUSIONS: High heregulin mRNA and high HER3 protein levels were found to independently correlate with poor OS in patients with OPSCC. These data support targeting HER3 in patients with heregulin-high OPSCC and warrant further clinical investigation.
Keywords:
epidermal growth factor receptor (EGFR); head and neck cancer; heregulin; human epidermal growth factor receptor 3 (HER3); human papillomavirus
Authors: Cleo Yi-Fang Lee; Yuan Lin; Scott V Bratman; Weiguo Feng; Angera H Kuo; Ferenc A Scheeren; Jesse M Engreitz; Sushama Varma; Robert B West; Maximilian Diehn Journal: Cancer Res Date: 2013-10-31 Impact factor: 12.701
Authors: Brian O'Sullivan; Shao Hui Huang; Lillian L Siu; John Waldron; Helen Zhao; Bayardo Perez-Ordonez; Ilan Weinreb; John Kim; Jolie Ringash; Andrew Bayley; Laura A Dawson; Andrew Hope; John Cho; Jonathan Irish; Ralph Gilbert; Patrick Gullane; Angela Hui; Fei-Fei Liu; Eric Chen; Wei Xu Journal: J Clin Oncol Date: 2013-01-07 Impact factor: 44.544
Authors: Atif J Khan; Bonnie L King; Benjamin D Smith; Grace L Smith; Michael P DiGiovanna; Darryl Carter; Bruce G Haffty Journal: Clin Cancer Res Date: 2002-02 Impact factor: 12.531
Authors: Mircea Romanitan; Anders Näsman; Eva Munck-Wikland; Tina Dalianis; Torbjörn Ramqvist Journal: Anticancer Res Date: 2013-04 Impact factor: 2.480
Authors: Mikiko Takikita; Ran Xie; Joon-Yong Chung; Hanbyoul Cho; Kris Ylaya; Seung-Mo Hong; Christopher A Moskaluk; Stephen M Hewitt Journal: J Transl Med Date: 2011-07-29 Impact factor: 5.531
Authors: David S Shames; Juliet Carbon; Kim Walter; Adrian M Jubb; Cleopatra Kozlowski; Tom Januario; An Do; Ling Fu; Yuanyuan Xiao; Rajiv Raja; Brittany Jiang; Ashi Malekafzali; Howard Stern; Jeff Settleman; Timothy R Wilson; Garret M Hampton; Robert L Yauch; Andrea Pirzkall; Lukas C Amler Journal: PLoS One Date: 2013-02-28 Impact factor: 3.240
Authors: Wenle Xia; Emanual F Petricoin; Sumin Zhao; Leihua Liu; Takuya Osada; Qing Cheng; Julia D Wulfkuhle; William R Gwin; Xiaoyi Yang; Rosa I Gallagher; Sarah Bacus; H Kim Lyerly; Neil L Spector Journal: Breast Cancer Res Date: 2013 Impact factor: 6.466
Authors: Dongsheng Wang; Guoqing Qian; Hongzheng Zhang; Kelly R Magliocca; Sreenivas Nannapaneni; A R M Ruhul Amin; Michael Rossi; Mihir Patel; Mark El-Deiry; J Trad Wadsworth; Zhengjia Chen; Fadlo R Khuri; Dong M Shin; Nabil F Saba; Zhuo G Chen Journal: Clin Cancer Res Date: 2016-06-29 Impact factor: 12.531
Authors: Conor E Steuer; Christopher C Griffith; Sreenivas Nannapaneni; Mihir R Patel; Yuan Liu; Kelly R Magliocca; Mark W El-Deiry; Cynthia Cohen; Taofeek K Owonikoko; Dong M Shin; Zhuo G Chen; Nabil F Saba Journal: Mol Cancer Ther Date: 2018-02-13 Impact factor: 6.261
Authors: Joyce F Liu; Isabelle Ray-Coquard; Frederic Selle; Andrés M Poveda; David Cibula; Hal Hirte; Felix Hilpert; Francesco Raspagliesi; Laurence Gladieff; Philipp Harter; Salvatore Siena; Josep Maria Del Campo; Isabelle Tabah-Fisch; Joseph Pearlberg; Victor Moyo; Kaveh Riahi; Rachel Nering; William Kubasek; Bambang Adiwijaya; Akos Czibere; R Wendel Naumann; Robert L Coleman; Ignace Vergote; Gavin MacBeath; Eric Pujade-Lauraine Journal: J Clin Oncol Date: 2016-10-23 Impact factor: 44.544
Authors: Nabil F Saba; Zhuo Gerogia Chen; Missak Haigentz; Paolo Bossi; Alessandra Rinaldo; Juan P Rodrigo; Antti A Mäkitie; Robert P Takes; Primoz Strojan; Jan B Vermorken; Alfio Ferlito Journal: Mol Cancer Ther Date: 2019-11 Impact factor: 6.261
Authors: Toni M Brand; Stefan Hartmann; Neil E Bhola; Noah D Peyser; Hua Li; Yan Zeng; Erin Isaacson Wechsler; Max V Ranall; Sourav Bandyopadhyay; Umamaheswar Duvvuri; Theresa M LaVallee; Richard C K Jordan; Daniel E Johnson; Jennifer R Grandis Journal: Clin Cancer Res Date: 2016-12-16 Impact factor: 12.531
Authors: Jose Mauricio Mota; Katharine Ann Collier; Ricardo Lima Barros Costa; Timothy Taxter; Aparna Kalyan; Caio A Leite; Young Kwang Chae; Francis J Giles; Benedito A Carneiro Journal: Oncotarget Date: 2017-06-13
Authors: Filip Radom; Clemens Vonrhein; Peer R E Mittl; Andreas Plückthun Journal: Acta Crystallogr F Struct Biol Commun Date: 2021-06-29 Impact factor: 1.056
Authors: Diego Alvarado; Gwenda F Ligon; Jay S Lillquist; Scott B Seibel; Gerald Wallweber; Veronique M Neumeister; David L Rimm; Gerald McMahon; Theresa M LaVallee Journal: PLoS One Date: 2017-07-19 Impact factor: 3.240