Yang Ellen, Alshamlan Najd, Hueniken Katrina, Weiss Jessica, Cabanero Michael, Tsao Ming-Sound
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Department of Pathology, University Health Network-Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
JTO Clin Res Rep. 2024 May 16;5(7):100682. doi: 10.1016/j.jtocrr.2024.100682. eCollection 2024 Jul.
Lepidic growth is considered noninvasive in lung nonmucinous adenocarcinoma, whereas other patterns are invasive. Considerable interobserver variability in assessing "invasion" has been reported. We assessed the utility of cytokeratin 7 (CK7) stain and recently proposed International Association for the Study of Lung Cancer criteria to improve assessment of noninvasion in lung adenocarcinoma.
Four pathologists (two staff, two trainees) assessed 158 hematoxylin and eosin (HE)- and CK7-stained slides of 108 pT1N0-2 nonmucinous lung adenocarcinoma cases. Scoring took place in four rounds. First, sections were independently scored for percentage of noninvasive or probable noninvasive and invasive or probable invasive patterns. Second, after a consensus scoring algorithm for CK7 was formulated, the slides were rescored. Subsequent third-round scoring was conducted only on HE slides using the 2023 International Association for the Study of Lung Cancer proposed criteria, and fourth-round scoring on both HE and CK7 slides simultaneously. Intraclass correlation coefficient (ICC) was calculated for each round. Recurrence-free survival was assessed using Cox proportional hazards regression methods.
In the first two rounds, interobserver concordance was consistently higher with CK7 (ICC range = 0.44-0.6) than HE (range = 0.24-0.49) scores. The IASLC proposed algorithm improved ICC of HE scores to 0.60 (95% confidence interval: 0.52-0.67), and round 4 HE and CK7 combined improved ICC to 0.75 (95% confidence interval: 0.70-0.80). Continuous measures of averaged noninvasive and probable noninvasive scores on HE were associated with improved recurrence-free survival (hazard ratio: 0.83-0.86).
CK7 staining consistently increased interobserver concordance in assessment of invasive versus noninvasive patterns than HE. Combining CK7 with the 2023 IASLC criteria for morphologic features of invasion may further improve the interobservers' concordance for the recognition of lepidic growth in nonmucinous lung adenocarcinoma.
在肺非黏液性腺癌中，鳞屑样生长被认为是无创性的，而其他模式则是浸润性的。据报道，在评估“浸润”方面存在相当大的观察者间差异。我们评估了细胞角蛋白7（CK7）染色和最近提出的国际肺癌研究协会标准在改善肺腺癌无创性评估中的效用。
四位病理学家（两名工作人员，两名实习生）评估了108例pT1N0-2非黏液性肺腺癌病例的158张苏木精和伊红（HE）染色及CK7染色切片。评分分四轮进行。首先，对切片中无创性或可能无创性以及浸润性或可能浸润性模式的百分比进行独立评分。其次，在制定了CK7的共识评分算法后，对切片重新评分。随后的第三轮评分仅使用2023年国际肺癌研究协会提出的标准对HE切片进行，第四轮评分同时对HE和CK7切片进行。计算每一轮的组内相关系数（ICC）。使用Cox比例风险回归方法评估无复发生存率。
在前两轮中，观察者间对CK7评分（ICC范围=0.44-0.6）的一致性始终高于HE评分（范围=0.24-0.49）。国际肺癌研究协会提出的算法将HE评分的ICC提高到0.60（95%置信区间：0.52-0.67），第四轮HE和CK7联合评分将ICC提高到0.75（95%置信区间：0.70-0.80）。HE上平均无创性和可能无创性评分的连续测量与改善的无复发生存率相关（风险比：0.83-0.86）。
与HE相比，CK7染色在评估浸润性与非浸润性模式时始终提高了观察者间的一致性。将CK7与2023年国际肺癌研究协会关于浸润形态学特征的标准相结合，可能会进一步提高观察者间对非黏液性肺腺癌中鳞屑样生长识别的一致性。
