Clauditz Till Sebastian, Böttcher Arne, Hanken Henning, Borgmann Kerstin, Sauter Guido, Wilczak Waldemar, Grob Tobias, Münscher Adrian
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
Department of Oto-, Rhino, Laryngology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
J Cancer Res Clin Oncol. 2018 Jan;144(1):53-61. doi: 10.1007/s00432-017-2528-x. Epub 2017 Oct 11.
FGFR1 is a receptor tyrosine kinases involved in tumor growth signaling, survival, and differentiation in many solid cancer types. There is growing evidence that FGFR1 amplification might predict therapy response to FGFR1 inhibitors in squamous cell lung cancers. To estimate the potential applicability of anti FGFR1 therapies in squamous cell carcinomas of the head and neck, we studied patterns of FGFR1 amplification using fluorescence in situ hybridization (FISH).
A tissue microarray was constructed from 453 primary treatment-naive squamous cell carcinomas of the head and neck regions with histopathological and clinical follow-up data [including oral cavity (n = 222), oropharynx (n = 126), and larynx (n = 105)]. FGFR1 and centromere 8 copy numbers were assessed by dual-color FISH. FGFR1 amplification was defined as a copy number ratio FGFR1: centromere 8 ≥ 2.0. HPV sequencing and p16 immunohistochemistry (IHC) were applied to FGFR1-amplified cancers.
FISH analysis was successful in 297 (66%) of the 453 cancers. FGFR1 amplification was found in 6% of analyzable tumors, and was more frequent in tumors of the oral cavity (13/133 amplified, 10%), than cancers of other localizations (1/79 oropharynx, 4/85 larynx; p = 0.007 and 0.159, respectively). One out of 18 FGFR1 amplified cancers was HPV positive. No associations were found between FGFR1 amplification and tumor phenotype or p16 IHC.
Head and neck cancers are recurrently affected by FGFR1 amplification, with a predominance in cancers of the oral cavity. Finding only one HPV positive and FGFR1 amplified cancer argues against a causal relationship between HPV and FGFR1 amplifications.
FGFR1是一种受体酪氨酸激酶，参与多种实体癌类型的肿瘤生长信号传导、存活和分化。越来越多的证据表明，FGFR1扩增可能预测肺鳞状细胞癌对FGFR1抑制剂的治疗反应。为了评估抗FGFR1疗法在头颈部鳞状细胞癌中的潜在适用性，我们使用荧光原位杂交（FISH）研究了FGFR1扩增模式。
构建了一个组织微阵列，其包含453例未经治疗的原发性头颈部鳞状细胞癌，并具有组织病理学和临床随访数据[包括口腔（n = 222）、口咽（n = 126）和喉（n = 105）]。通过双色FISH评估FGFR1和8号染色体着丝粒的拷贝数。FGFR1扩增定义为拷贝数比FGFR1:着丝粒8≥2.0。对FGFR1扩增的癌症进行HPV测序和p16免疫组织化学（IHC）检测。
453例癌症中有29７例（66%）成功进行了FISH分析。在可分析的肿瘤中，6%发现有FGFR1扩增，在口腔肿瘤中更常见（133例中有13例扩增，10%），高于其他部位的癌症（口咽1/79例，喉4/85例；p分别为0.007和0.159）。18例FGFR1扩增的癌症中有1例HPV阳性。未发现FGFR1扩增与肿瘤表型或p16 IHC之间存在关联。
头颈部癌症经常受到FGFR1扩增的影响，在口腔癌中占主导地位。仅发现1例HPV阳性且FGFR1扩增的癌症，这表明HPV与FGFR1扩增之间不存在因果关系。
