Koole Koos, Clausen Martijn J A M, van Es Robert J J, van Kempen Pauline M W, Melchers Lieuwe J, Koole Ron, Langendijk Johannes A, van Diest Paul J, Roodenburg Jan L N, Schuuring Ed, Willems Stefan M
Department of Pathology, University Medical Center Utrecht, H4.2.41, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
Department of Head and Neck Surgical Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
Mol Diagn Ther. 2016 Aug;20(4):363-74. doi: 10.1007/s40291-016-0204-5.
Fibroblast growth factor receptor family member proteins (FGFR1-4) have been identified as promising novel therapeutic targets and prognostic markers in a wide spectrum of solid tumors. The present study investigates the expression and prognostic value of four FGFR family member proteins in a large multicenter oral cavity squamous cell carcinoma (OCSCC) and oropharyngeal squamous cell carcinoma (OPSCC) cohort.
Protein expression of FGFR1-4 was determined by immunohistochemistry on tissue microarrays containing 951 formalin-fixed paraffin embedded OCSCC and OPSCC tissues from the University Medical Center Utrecht and University Medical Center Groningen. Protein expression was correlated to overall survival using Cox regression models, and bootstrapping was performed as internal validation.
FGFR proteins were highly expressed in 39-64 % of OCSCC and 63-79 % of OPSCC. Seventy-three percent (299/412) of OCSCC and 85 % (305/357) of OPSCC highly co-expressed two or more FGFR family member proteins. FGFR1 protein was more frequently highly expressed in human papillomavirus (HPV)-negative OPSCC than HPV-positive OPSCC (82 vs. 65 %; p = 0.008). Furthermore, protein expression of FGFR family members was not related to overall survival in OCSCC or OPSCC (p > 0.05).
FGFR family members are frequently highly expressed in OCSCC and OPSCC. These FGFR family member proteins are therefore potential targets for novel therapies that are urgently required to improve survival of OCSCC and OPSCC patients.
成纤维细胞生长因子受体家族成员蛋白(FGFR1 - 4)已被确定为多种实体瘤中有前景的新型治疗靶点和预后标志物。本研究调查了四种FGFR家族成员蛋白在一个大型多中心口腔鳞状细胞癌(OCSCC)和口咽鳞状细胞癌(OPSCC)队列中的表达及预后价值。
通过免疫组织化学法在组织微阵列上测定FGFR1 - 4的蛋白表达,该组织微阵列包含来自乌得勒支大学医学中心和格罗宁根大学医学中心的951例福尔马林固定石蜡包埋的OCSCC和OPSCC组织。使用Cox回归模型将蛋白表达与总生存期相关联,并进行自举法作为内部验证。
FGFR蛋白在39% - 64%的OCSCC和63% - 79%的OPSCC中高表达。73%(299/412)的OCSCC和85%(305/357)的OPSCC高共表达两种或更多种FGFR家族成员蛋白。FGFR1蛋白在人乳头瘤病毒(HPV)阴性的OPSCC中比HPV阳性的OPSCC更频繁地高表达(82%对65%;p = 0.008)。此外,FGFR家族成员的蛋白表达与OCSCC或OPSCC中的总生存期无关(p > 0.05)。
FGFR家族成员在OCSCC和OPSCC中经常高表达。因此,这些FGFR家族成员蛋白是新型疗法的潜在靶点,而新型疗法是改善OCSCC和OPSCC患者生存率迫切需要的。