Department of Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia; Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, New South Wales, Australia.
School of Mathematics and Statistics, The University of Sydney, Sydney, New South Wales, Australia; Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.
Mod Pathol. 2023 Aug;36(8):100190. doi: 10.1016/j.modpat.2023.100190. Epub 2023 Apr 18.
Squamous cell carcinoma is the most common head and neck malignancy arising from the oral mucosa and the skin. The histologic and immunohistochemical features of oral squamous cell carcinoma (OSCC) and head and neck cutaneous squamous cell carcinoma (HNcSCC) are similar, making it difficult to identify the primary site in cases of metastases. With the advent of immunotherapy, reliable distinction of OSCC and HNcSCC at metastatic sites has important treatment and prognostic implications. Here, we investigate and compare the genomic landscape of OSCC and HNcSCC to identify diagnostically useful biomarkers. Whole-genome sequencing data from 57 OSCC and 41 HNcSCC patients were obtained for tumor and matched normal samples. Tumor mutation burden (TMB), Catalogue of Somatic Mutations in Cancer (COSMIC) mutational signatures, frequent chromosomal alterations, somatic single nucleotide, and copy number variations were analyzed. The median TMB of 3.75 in primary OSCC was significantly lower (P < .001) than that of 147.51 mutations/Mb in primary HNcSCC. The COSMIC mutation signatures were significantly different (P < .001) between OSCC and HNcSCC. OSCC showed COSMIC single-base substitution (SBS) mutation signature 1 and AID/APOBEC activity-associated signature 2 and/or 13. All except 1 HNcSCC from hair-bearing scalp showed UV damage-associated COSMIC SBS mutation signature 7. Both OSCC and HNcSCC demonstrated a predominance of tumor suppressor gene mutations, predominantly TP53. The most frequently mutated oncogenes were PIK3CA and MUC4 in OSCC and HNcSCC, respectively. The metastases of OSCC and HNcSCC demonstrated TMB and COSMIC SBS mutation signatures similar to their primary counterparts. The combination of high TMB and UV signature in a metastatic keratinizing squamous cell carcinoma suggests HNcSCC as the primary site and may also facilitate decisions regarding immunotherapy. HNcSCC and OSCC show distinct genomic profiles despite histologic and immunohistochemical similarities. Their genomic characteristics may underlie differences in behavior and guide treatment decisions in recurrent and metastatic settings.
鳞状细胞癌是最常见的头颈部恶性肿瘤，起源于口腔黏膜和皮肤。口腔鳞状细胞癌 (OSCC) 和头颈部皮肤鳞状细胞癌 (HNcSCC) 的组织学和免疫组织化学特征相似，因此在转移病例中很难确定原发部位。随着免疫疗法的出现，在转移性部位可靠地区分 OSCC 和 HNSCC 具有重要的治疗和预后意义。在这里，我们研究并比较了 OSCC 和 HNSCC 的基因组图谱，以确定具有诊断价值的生物标志物。从 57 名 OSCC 和 41 名 HNSCC 患者的肿瘤和匹配的正常样本中获得了全基因组测序数据。分析了肿瘤突变负荷 (TMB)、癌症体细胞突变目录 (COSMIC) 突变特征、常见染色体改变、体细胞单核苷酸和拷贝数变异。原发性 OSCC 的中位 TMB 为 3.75，明显低于原发性 HNSCC 的 147.51 突变/Mb（P <.001）。OSCC 和 HNSCC 的 COSMIC 突变特征明显不同（P <.001）。OSCC 显示 COSMIC 单碱基替换 (SBS) 突变特征 1 和 AID/APOBEC 活性相关特征 2 和/或 13。除了来自有毛发头皮的 1 例 HNSCC 外，所有 HNSCC 均显示与紫外线损伤相关的 COSMIC SBS 突变特征 7。OSCC 和 HNSCC 均显示肿瘤抑制基因突变为主，主要是 TP53。最常突变的癌基因分别是 OSCC 中的 PIK3CA 和 HNSCC 中的 MUC4。OSCC 和 HNSCC 的转移灶表现出与原发性肿瘤相似的 TMB 和 COSMIC SBS 突变特征。在转移性角化鳞状细胞癌中，高 TMB 与 UV 特征的结合提示 HNSCC 为原发性肿瘤，也可能有助于免疫治疗决策。尽管组织学和免疫组织化学相似，但 HNSCC 和 OSCC 显示出明显不同的基因组谱。它们的基因组特征可能是行为差异的基础，并指导复发性和转移性疾病的治疗决策。
