Abstract：
Positron emission tomography is a useful technique for diagnosing lymph node (LN) metastasis. This study aimed to elucidate the association between fluorodeoxyglucose accumulation and the microenvironment in metastatic LNs in lung adenocarcinoma. We retrospectively analyzed 62 patients with surgically resected pathological N2 lung adenocarcinoma who underwent preoperative PET. The maximum standardized uptake value (SUVmax ) in the metastatic LNs was measured. Lymph node specimens were immunohistochemically analyzed for CD8+ , FoxP3+ , and CD79a+ lymphocytes, CD204+ tumor-associated macrophages (TAMs), and alpha-smooth muscle actin-positive cancer-associated fibroblasts (αSMA+ CAFs). We compared the clinicopathologic and immunohistochemical characteristics between two groups with high and low LN SUVmax . Using novel 3D hybrid spheroid models, we investigated the change in invasiveness of cancer cells in the presence of CAFs. In the multivariate analyses, LN SUVmax was an independent prognostic factor. The overall survival in the LN SUVmax high group was significantly worse than in the low group (P = .034). In the LN SUVmax high group, metastatic cancer cell invasion of extranodal tissue was more frequent (P = .005) and the number of CD204+ TAMs and αSMA+ CAFs in metastatic LNs was significantly higher than in the low group (P < .001 and P = .002, respectively). Hybrid spheroid models revealed that cancer cells coexisting with CAFs were more invasive than those without CAFs. Our results indicated a strong association between LN SUVmax and poor prognosis in patients with N2 lung adenocarcinoma. Moreover, LN SUVmax was suggested to be associated with the presence of tumor-promoting stromal cells in metastatic LNs.
摘要：
正电子发射断层扫描是诊断淋巴结（LN）转移的有用技术。这项研究旨在阐明氟脱氧葡萄糖积累与肺腺癌转移性LNs微环境之间的关系。我们回顾性分析了62例经手术切除的病理性N2肺腺癌患者，这些患者术前接受了PET。测量转移性LN中的最大标准化摄取值(SUVmax)。淋巴结标本进行CD8+免疫组织化学分析，FoxP3+,和CD79a+淋巴细胞，CD204+肿瘤相关巨噬细胞（TAMs），和α-平滑肌肌动蛋白阳性癌症相关成纤维细胞（αSMA+CAF）。我们比较了高和低LNSUVmax两组的临床病理和免疫组织化学特征。使用新颖的3D混合球体模型，我们研究了在CAFs存在下癌细胞侵袭性的变化.在多变量分析中，LNSUVmax是独立的预后因素。LNSUVmax高组的总生存率明显低于低组（P=0.034）。在LNSUVmax高组中，转移性癌细胞对结外组织的侵袭频率更高（P=0.005），转移性LN中CD204TAMs和αSMACAFs的数量明显高于低组（分别为P<0.001和P=0.002）。混合球体模型显示，与CAF共存的癌细胞比没有CAF的癌细胞更具侵袭性。我们的结果表明，N2肺腺癌患者的LNSUVmax与不良预后之间存在很强的相关性。此外，LNSUVmax被认为与转移性LN中肿瘤促进基质细胞的存在有关。
