Center for Head & Neck Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room 2128, Boston, MA, 02215, USA.
J Transl Med. 2024 Oct 22;22(1):960. doi: 10.1186/s12967-024-05761-z.
Brain metastasis (BM) is a rare but severe complication of head and neck squamous cell carcinoma (HNSCC), with limited knowledge of molecular characteristics and immunogenicity.
We analyzed 61 cases of HNSCC-BM from three academic institutions (n = 24) and Foundation Medicine Inc (FMI, n = 37). A subset of cases underwent next-generation sequencing, multiple immunofluorescence, and proximity ligation sequencing. Gene enrichment analysis compared alterations in FMI BM samples (n = 37) with local samples (n = 4082).
Demographics included: median age of 59 years, 75% male, 55% current/former smokers, 75% oropharyngeal primary, and 67% human papillomavirus (HPV) +. ATM (54%), KMT2A (54%), PTEN (46%), RB1 (46%), and TP53 (46%) were frequently altered in BM samples from academic centers (62% HPV/p16+). Structural rearrangements ranged from 9 to 90 variants by proximity ligation sequencing. BMs had low densities of CD8+, PD-1+, PD-L1+, and FOXP3 + cells, and 92% had PD-L1 combined positive scores < 1%. CDKN2A (40.5%), TP53 (37.8%), and PIK3CA (27.0%) alterations were common in the FMI BMs (51% HPV+). MAP2K2 alterations and HPV + signature were enriched in FMI BMs compared to local tumors (11.8% vs. 6.4%, P = 0.005 and 51.25% vs. 26.11%, P = 0.001 respectively), and pathogenic TSC1 inactivating mutations were enriched in local tumors (67.3% vs. 37.8%, P = 0.008). Median overall survival from BM diagnosis was 9 months (range 0-27).
HNSCC patients with BM frequently have oropharyngeal primary sites and are HPV+. Common molecular alterations in BM samples, including targetable PIK3CA and ATM, were identified. MAP2K2 alterations were enriched and densities of immune cells were low, highlighting potential targets for further research and immunotherapy considerations.
脑转移（BM）是头颈部鳞状细胞癌（HNSCC）的一种罕见但严重的并发症，对其分子特征和免疫原性知之甚少。
我们分析了来自三个学术机构的 61 例 HNSCC-BM 病例（n=24）和 Foundation Medicine Inc（FMI，n=37）。一部分病例进行了下一代测序、多种免疫荧光和邻近连接测序。基因富集分析比较了 FMI BM 样本（n=37）与局部样本（n=4082）的改变。
人口统计学特征包括：中位年龄 59 岁，75%为男性，55%为现/ former 吸烟者，75%为口咽原发癌，67%为 HPV+。在学术中心的 BM 样本中，ATM（54%）、KMT2A（54%）、PTEN（46%）、RB1（46%）和 TP53（46%）经常发生改变（62% HPV/p16+）。通过邻近连接测序，结构重排的范围从 9 到 90 个变体。BM 中 CD8+、PD-1+、PD-L1+和 FOXP3+细胞密度低，92%的 PD-L1 联合阳性评分<1%。CDKN2A（40.5%）、TP53（37.8%）和 PIK3CA（27.0%）的改变在 FMI BM 中很常见（51% HPV+）。与局部肿瘤相比，FMI BM 中 MAP2K2 改变和 HPV+ 特征更为丰富（11.8%比 6.4%，P=0.005 和 51.25%比 26.11%，P=0.001），而局部肿瘤中 TSC1 致病性失活突变更为丰富（67.3%比 37.8%，P=0.008）。从 BM 诊断到死亡的中位总生存期为 9 个月（0-27 个月）。
HNSCC 伴 BM 的患者常为口咽原发癌且为 HPV+。在 BM 样本中发现了常见的分子改变，包括可靶向的 PIK3CA 和 ATM。MAP2K2 改变丰富，免疫细胞密度低，突出了进一步研究和免疫治疗考虑的潜在靶点。
