Diagnostic imaging of typical lung carcinoids: relationship between MDCT, 111In-Octreoscan and 18F-FDG-PET imaging features with Ki-67 index.
典型肺类癌的诊断成像: MDCT、 111in-奥曲肽oscan和 18F-FDG-PET成像特征与Ki-67 指数的关系。
- 作者列表："Danti G","Berti V","Abenavoli E","Briganti V","Linguanti F","Mungai F","Pradella S","Miele V
AIMS:This study analyses the capability of contrast-enhanced multi-detector computed tomography (MDCT) and spectrum of molecular imaging to characterize typical carcinoids (TCs) of lung and their relationship with Ki-67 index. MATERIALS AND METHODS:We analysed 68 patients with histological diagnosis of pulmonary TC, which underwent both MDCT and nuclear molecular imaging (somatostatin receptor scintigraphy/SPECT with 111In-pentetreotide and 18F-FDG-PET/CT) at staging evaluation before surgery. The MDCT scan was reviewed for the following features: size, margins, contrast enhancement, presence of calcifications, bronchial obstruction, lymph nodes and metastases. In 111In-pentetreotide SPECT, tumour/non-tumour ratio was measured at 4- and 24-h post-injection and the per cent difference was calculated (T/NT%). FDG uptake was measured as the ratio between lesion SUVmax and liver SUVmean (SUV ratio). All imaging features were correlated between them and with Ki-67 index. RESULTS:Forty-four of the 68 lesions (65%) were in the right lung. In MDCT, scan lesions appeared as a well-defined nodule in 44 patients (65%) and irregular mass in 24 patients (35%). Contrast intense enhancement was present in 53 patients (78%), calcifications in 20 patients (29%) and bronchial obstruction in 24 patients (35%). Lymph nodes and metastasis were present in 13 (19%) and 15 (22%) patients. Ki-67 index was negatively correlated with T/NT% and positively with SUV ratio; T/NT% and SUV ratio were inversely correlated. The presence of irregular margins and metastases was negatively related to T/NT%. The presence of a mass, irregular margins, bronchial obstruction, lymph nodes and metastasis was positively related to higher SUV ratio. The presence of irregular margins, bronchial obstruction, lymph nodes and metastases was significantly correlated with a higher grade of Ki-67 index. CONCLUSIONS:MDCT and nuclear molecular imaging are important to characterize lung TCs. The majority of TCs appear as a well-defined nodule generally not associated with extra-thorax signs. We found a significant correlation between some MDCT aspects, nuclear medicine features and Ki-67 index. The association of MDCT and nuclear medicine imaging may be useful in predicting proliferative activity and prognosis of lung TCs.
目的: 本研究分析对比增强多排螺旋ct (MDCT) 和分子影像谱表征肺典型类癌 (TCs) 的能力及其与Ki-67 指数的关系。 材料和方法: 我们分析了 68 例组织学诊断为肺TC的患者，这些患者同时接受了MDCT和核分子显像 (生长抑素受体显像/SPECT联合 111In-pentetreotide和 18F-FDG-PET/CT) 术前分期评估。回顾MDCT扫描的以下特征: 大小，边缘，对比增强，钙化的存在，支气管阻塞，淋巴结和转移。在 111In-pentetreotide SPECT中，在注射后 4 小时和 24 小时测量肿瘤/非肿瘤比率，并计算百分比差异 (T/NT %)。FDG摄取被测量为病灶SUVmax和肝脏SUVmean之间的比率 (SUV比率)。所有成像特征之间具有相关性，并且具有Ki-67 指数。 结果: 68 个病灶中有 44 个病灶 (65%) 位于右肺。在MDCT中，44 例患者 (65%) 的扫描病灶表现为明确的结节，24 例患者 (35%) 的不规则肿块。对比强增强 53 例 (78%)，钙化 20 例 (29%)，支气管阻塞 24 例 (35%)。13 例 (19%) 和 15 例 (22%) 患者有淋巴结转移。Ki-67 指数与T/NT % 呈负相关，与SUV比值呈正相关; T/NT % 与SUV比值呈负相关。不规则边缘和转移的存在与T/NT % 呈负相关。肿块、不规则边缘、支气管阻塞、淋巴结和转移的存在与较高的SUV比率正相关。不规则边缘、支气管阻塞、淋巴结和转移的存在与Ki-67 指数的较高级别显著相关。 结论: MDCT和核分子成像对肺TCs的特征是重要的。大多数TCs表现为明确的结节，通常与胸外体征无关。我们发现一些MDCT方面、核医学特征和Ki-67 指数之间存在显著相关性。MDCT与核医学成像的相关性可能有助于预测肺TCs的增殖活性和预后。
METHODS::Pulmonary artery sling is a rare congenital anomaly of the origin and course of the left pulmonary artery. Patients with this condition typically present with respiratory failure in young infancy, and asymptomatic cases are uncommon. We describe the case of an adult patient with a lung adenocarcinoma of the right upper lobe, extending into the hilum and superior mediastinum, and with a previously unknown pulmonary artery sling anomaly. The local invasiveness of the tumor and the peculiar vascular anatomy contributed to a unique surgical scenario, wherein multiple reconstructive procedures were required.
METHODS::Patients with idiopathic pulmonary fibrosis (IPF) have higher risk of developing lung cancer, for example, squamous cell carcinoma (SCC), and show poor prognosis, while the molecular basis has not been fully investigated. Here we conducted DNA methylome analysis of lung SCC using 20 SCC samples with/without IPF, and noncancerous lung tissue samples from smokers/nonsmokers, using Infinium HumanMethylation 450K array. SCC was clustered into low- and high-methylation epigenotypes by hierarchical clustering analysis. Genes hypermethylated in SCC significantly included genes targeted by polycomb repressive complex in embryonic stem cells, and genes associated with Gene Ontology terms, for example, "transcription" and "cell adhesion," while genes hypermethylated specifically in high-methylation subgroup significantly included genes associated with "negative regulation of growth." Low-methylation subgroup significantly correlated with IPF (78%, vs. 17% in high-methylation subgroup, p = 0.04), and the correlation was validated by additional Infinium analysis of SCC samples (n = 44 in total), and data from The Cancer Genome Atlas (n = 390). The correlation between low-methylation subgroup and IPF was further validated by quantitative methylation analysis of marker genes commonly hypermethylated in SCC (HOXA2, HOXA9 and PCDHGB6), and markers specifically hypermethylated in high-methylation subgroup (DLEC1, CFTR, MT1M, CRIP3 and ALDH7A1) in 77 SCC cases using pyrosequencing (p = 0.003). Furthermore, low-methylation epigenotype significantly correlated with poorer prognosis among all SCC patients, or among patients without IPF. Multivariate analysis showed that low-methylation epigenotype is an independent predictor of poor prognosis. These may suggest that lung SCC could be stratified into molecular subtypes with distinct prognosis, and low-methylation lung SCC that significantly correlates with IPF shows unfavorable outcome.
METHODS::The role of Fyn-related kinase (FRK) in malignant tumors remains controversial. Our study investigated the function of FRK in lung cancer. Immunohistochemistry staining and generating a knockout of FRK by CRISPR/Cas9 in H1299 (FRK-KO-H1299) cells were strategies used to explore the role of FRK. Immunohistochemistry staining indicated that FRK expression was elevated in 223 lung cancer tissues compared to 26 distant normal lung tissues. FRK contributed to poor survival status in lung cancer patients and acted as a predictor for poor prognosis of lung cancer. Knockout of FRK by CRISPR/Cas9 markedly inhibited proliferation, invasion, colony formation and epithelial-mesenchymal transition (EMT) process in the lung cancer cell line H1299. Further exploration indicated that FRK-KO damaged the stemness phenotype of H1299 by inhibiting CD44 and CD133 expression. Seahorse detection and a U-13 C flux assay revealed that FRK-KO induced metabolism reprogramming by inhibiting the Warburg effect and changing the energy type in H1299 cells. Epidermal growth factor stimulation recovered the expression of FRK and biological functions, metabolic reprogramming and stemness phenotype of H1299 cells. FRK plays an oncogenic role in lung cancer cells via a novel regulation mechanism of enhancing the stemness of H1299 cells by inducing metabolism reprogramming, which finally promotes EMT and metastasis. Our study also indicates that FRK could be used as a potential therapeutic target for drug development.