肺鱗癌中腫瘤細胞的芽殖和STAS:最佳預後截點的確定和驗證

我們確定了SCC-L患者的最佳分界點,並確定了TCB和點(STA灶個數、牙槽內STA距離)是獨立且不相關的預後因素。

Tumour Cell Budding and Spread Through Air Spaces in Squamous Cell Carcinoma of the Lung – Determination and Validation of optimal prognosticcut-offs

 (Lung Cancer, IF: 5.731)

Stögbauer, M. Lautizi, M. Kriegsmann, H. Winter, T. Muley, K. Kriegsmann, M.Jesinghaus, J. Baumbach, P. Schüffler, W. Weichert, T. Kacprowski, M. Boxberg, Tumour Cell Budding and Spread Through Air Spaces in Squamous Cell Carcinoma of the Lung – Determination and Validation of optimal prognostic cut-offs, Lung Cancer (2022), doi: https://doi.org/10.1016/j.lungcan.2022.04.012

Purpose 目的

Prognostic stratification of patients with squamous cell carcinomas of the lung (SCC-L) is challenging. Therefore, we investigated several histomorphological parameters (tumour cell budding (TCB), spread through air spaces (STAS), tumour-stroma-ratio, immune cell infiltration) which could potentially serve as prognostic parameters in SCC-L. We aimed to systematically determine optimal cut-off-values and assess the prognostic capability of these patterns. We furthermore assessed interobserver variability (IOV) for prognostically significant patterns TCB and STAS.

肺鱗狀細胞癌(SCC-L)患者的預後分層具有挑戰性。因此,我們研究了幾個可能作為SCC-L預後參數的組織形態學參數(腫瘤細胞出芽(TCB),通過空氣擴散(STAS),腫瘤基質比,免疫細胞浸潤)。我們的目標是系統地確定最佳臨界值,並評估這些模式的預後能力。我們進一步評估了具有預測意義的TCB和STAS模式的觀察者間可變性(IOV)。

Experimental Design 實驗設計

The Cancer Genome Atlas (TCGA) study cohort consisted of 335 patients with SCC-L. Histomorphological parameters analysed comprised TCB, minimal cell nest size (MCNS), STAS, stroma content and immune cell infiltration. The most significant cut-off-values were determined and univariate and multivariate survival outcomes were estimated. The identified cut-off-points were validated in an independent SCC-L cohort (n=346 patients). Two experienced pathologists probed IOV in the validation cohort.

腫瘤基因組圖譜(TCGA)研究隊列包括335例鱗癌-L患者。分析的組織形態參數包括TCB、最小細胞巢大小(MCNS)、STAS、基質含量和免疫細胞浸潤。確定了最顯著的臨界值,並估計了單變數和多變數的生存結果。確定的分界點在獨立的SCC-L隊列中得到驗證(n=346名患者)。兩位經驗豐富的病理學家在驗證隊列中檢測了IOV。

Results 結果

In the TCGA study cohort, TCB, STAS and immune cell infiltration were identified as significant prognostic parameters.  TCB-high tumours, a high number of STAS  foci,  extensive  STAS  for distance  of  STAS  in  alveoli  and  a  low  immune  cell  infiltration  remained  as  independent prognostic factors in multivariate Cox proportional hazard analyses for overall survival (OS). The significance of TCB, number of STAS foci and distance of STAS in alveoli for OS could be validated in the validation cohort. IOV reached a Kappa 點0.89 for prognostic parameters.

在TCGA研究隊列中,TCB、STAS和免疫細胞浸潤被確定為重要的預後參數。在對總體生存(OS)進行的多因素Cox比例風險分析中,腫瘤TCB高、STA灶數目多、肺泡STA距離大、免疫細胞浸潤率低仍是獨立的預後因素。在驗證隊列中可以驗證TCB、STA病灶數目和肺泡內STAS距離對OS的意義,IOV達到Kappa點0.89的預後參數。

Conclusions 結論

We determined optimal cut-offs and identified TCB and STAS (number of STAS foci, distance of STAS in alveoli) as independent and uncorrelated prognostic factors for patients with SCC-L. The significance was validated in a large independent cohort. IOV was almost perfect for prognostic parameters. We propose the application of TCB- and STAS-based grading in SCC-L as prognostic morphological classifiers.

Key words:Prognosis; Lung cancer; Histomorphology; Budding; STAS

我們確定了SCC-L患者的最佳分界點,並確定了TCB和點(STA灶個數、牙槽內STA距離)是獨立且不相關的預後因素。這一重要性在一個大型的獨立隊列中得到了驗證。IOV對於預後參數幾乎是完美的。我們建議在SCC-L中應用基於TCB和STAS的分級作為預後的形態分類。

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