背景:肺癌(LC)是恶性肿瘤中发病率和死亡率的主要原因。改善LC的诊断和治疗仍然是现代肿瘤学的紧迫任务。以前,我们确定在胃中,乳腺癌和宫颈癌,肿瘤微血管(MV)的形态不同,具有不同的预后意义。不同类型的肿瘤MV与LC进展之间的联系尚不清楚。
目的:探讨肺鳞状细胞癌(LUSC)组织形态特征及其临床意义。
方法:一项单中心回顾性队列研究检查了62名和180名I-IIIA期LUSC患者在训练和主要队列中的病历和存档石蜡块,分别。从2009年5月20日至2021年12月14日,所有患者在奥伦堡地区癌症诊所接受了根治性手术(R0)。常规处理肿瘤切片,和常规Mayer的苏木精和伊红染色和免疫组织化学染色的分化簇34(CD34),podoplanin,进行蜗牛和缺氧诱导因子-1α。不同类型肿瘤MVs的形态学特征,根据临床病理特征和LUSC预后研究肿瘤实质和间质。采用Statistica10.0软件进行统计分析。进行单变量和多变量逻辑回归分析,以确定LUSC转移到区域淋巴结(RLN)和疾病复发的潜在危险因素。构建了受试者工作特征曲线,以区分RLN中有和没有转移的患者以及有和没有疾病复发的患者。通过曲线下面积评估预测模型的有效性。使用Kaplan-Meier方法分析存活率。使用对数秩检验比较患者亚组之间的生存曲线。P<0.05的值被认为指示统计学显著性。
结果:根据形态,我们将肿瘤血管分为以下类型:正常MV,扩张的毛细血管(DC),非典型DC,CD34弱表达的DC,“接触型”DC,具有部分内皮衬里的结构,肿瘤实体成分中的毛细血管和淋巴样和多形细胞浸润中的淋巴管。我们还评估了松动的存在,肿瘤间质中的细纤维结缔组织(LFFCT)和回缩裂隙,肿瘤扩散到肺泡空气空间(AAS)和肿瘤实体成分的碎片。根据多变量分析,RLN中LUSC转移的独立预测因素是中心肿瘤位置(P<0.00001),回缩裂痕的存在(P=0.003),肿瘤实体成分中的毛细血管(P=0.023)和肿瘤实体成分中的碎片(P=0.009),而LUSC复发的独立预测因子是肿瘤3级(G3)(P=0.001),N2级(P=0.016),肿瘤间质中存在LFFCT(P<0.00001),肿瘤实体成分的碎裂(P=0.0001),并且没有肿瘤通过AAS扩散(P=0.0083)。
结论:获得的结果证实了我们先前提出的不同类型肿瘤血管分类的正确性,并可能有助于改善LUSC的诊断和治疗。
BACKGROUND: Lung cancer (LC) is the leading cause of morbidity and mortality among malignant neoplasms. Improving the diagnosis and treatment of LC remains an urgent task of modern oncology. Previously, we established that in gastric, breast and cervical cancer, tumor microvessels (MVs) differ in morphology and have different prognostic significance. The connection between different types of tumor MVs and the progression of LC is not well understood.
OBJECTIVE: To evaluate the morphological features and clinical significance of tumor MVs in lung squamous cell carcinoma (LUSC).
METHODS: A single-center retrospective cohort study examined medical records and archival paraffin blocks of 62 and 180 patients with stage I-IIIA LUSC in the training and main cohorts, respectively. All patients underwent radical surgery (R0) at the Orenburg Regional Cancer Clinic from May/20/2009 to December/14/2021. Tumor sections were routinely processed, and routine Mayer\'s hematoxylin and eosin staining and immunohistochemical staining for cluster of differentiation 34 (CD34), podoplanin, Snail and hypoxia-inducible factor-1 alpha were performed. The morphological features of different types of tumor MVs, tumor parenchyma and stroma were studied according to clinicopathological characteristics and LUSC prognosis. Statistical analysis was performed using Statistica 10.0 software. Univariate and multivariate logistic regression analyses were performed to identify potential risk factors for LUSC metastasis to regional lymph nodes (RLNs) and disease recurrence. Receiver operating characteristic curves were constructed to discriminate between patients with and without metastases in RLNs and those with and without disease recurrence. The effectiveness of the predictive models was assessed by the area under the curve. Survival was analyzed using the Kaplan-Meier method. The log-rank test was used to compare survival curves between patient subgroups. A value of P < 0.05 was considered to indicate statistical significance.
RESULTS: Depending on the morphology, we classified tumor vessels into the following types: normal MVs, dilated capillaries (DCs), atypical DCs, DCs with weak expression of CD34, \"contact-type\" DCs, structures with partial endothelial linings, capillaries in the tumor solid component and lymphatic vessels in lymphoid and polymorphocellular infiltrates. We also evaluated the presence of loose, fine fibrous connective tissue (LFFCT) and retraction clefts in the tumor stroma, tumor spread into the alveolar air spaces (AASs) and fragmentation of the tumor solid component. According to multivariate analysis, the independent predictors of LUSC metastasis in RLNs were central tumor location (P < 0.00001), the presence of retraction clefts (P = 0.003), capillaries in the tumor solid component (P = 0.023) and fragmentation in the tumor solid component (P = 0.009), whereas the independent predictors of LUSC recurrence were tumor grade 3 (G3) (P = 0.001), stage N2 (P = 0.016), the presence of LFFCT in the tumor stroma (P < 0.00001), fragmentation of the tumor solid component (P = 0.0001), and the absence of tumor spread through the AASs (P = 0.0083).
CONCLUSIONS: The results obtained confirm the correctness of our previously proposed classification of different types of tumor vessels and may contribute to improving the diagnosis and treatment of LUSC.