早期肺腺癌的原位生长可能代表前体生长或侵入性克隆生长——临床相关的区别。,Modern Pathology

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早期肺腺癌的原位生长可能代表前体生长或侵入性克隆生长——临床相关的区别。
Modern Pathology ( IF 7.1 ) Pub Date : 2019-04-01 , DOI: 10.1038/s41379-019-0257-1
David Allan Moore _{1,

2} , Marco Sereno _{3,

4} , Madhumita Das ₃ , Juvenal Dario Baena Acevedo ₄ , Samantha Sinnadurai ₄ , Claire Smith _{3,

4} , Abi McSweeney ₄ , Xiaoyu Su ₄ , Leah Officer ₃ , Carolyn Jones ₃ , Kate Dudek ₃ , David Guttery ₄ , Phillipe Taniere ₅ , Ruth V Spriggs ₃ , John Le Quesne _{3,

4,

6}

Affiliation

从原位肿瘤生长到浸润性肿瘤生长的转变代表了肺腺癌演变的关键阶段。然而，对这种转变的生物学理解是有限的，“Noguchi C 型”肿瘤是原位和浸润性混合生长的早期肺腺癌，代表了那些对促进我们对这一过程的理解非常有价值的肿瘤。对来自 LATTICE-A 队列的所有 Noguchi C 型腺癌 (n = 110) 进行了审查，并确定了两种原位肿瘤生长模式：那些被认为可能代表从原位癌前体到浸润性疾病的真正转变（'Noguchi C1'）以及那些贴壁成分似乎代表侵袭性肿瘤沿现有空域生长的那些（'Noguchi C2'）。C2 肿瘤的总体 Ki67 分数更高，只有 C1 肿瘤显示从原位到侵袭性疾病的 Ki67 显着增加。P53 阳性是从 C1 肿瘤的原位到侵袭性疾病获得的，但两种成分在 C2 肿瘤中均为阳性。同样，波形蛋白表达仅在 C1 肿瘤中从原位增加到浸润性肿瘤。18 个 C1 肿瘤的靶向下一代测序确定了侵入区域的四个私有突变，包括 TP53 中的两个突变，而 6 个 C2 肿瘤未显示私有突变。在完整的 LATTICe-A 队列中，Ki67 分数在肺腺癌的原位成分中被归类为小于或大于 10%，被确定为患者预后的强预测因子。这支持了具有“高级别”的所有阶段的肿瘤的命题原位成分代表那些具有侵入性克隆侵袭性贴壁生长的成分。总体而言，这些数据支持 Noguchi C 肿瘤的联合生长可以代表两种不同的生物学状态，并且“Noguchi C1”肿瘤代表了从原位到侵袭性疾病的真正生物学转变。

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In situ growth in early lung adenocarcinoma may represent precursor growth or invasive clone outgrowth-a clinically relevant distinction.

The switch from in situ to invasive tumor growth represents a crucial stage in the evolution of lung adenocarcinoma. However, the biological understanding of this shift is limited, and 'Noguchi Type C' tumors, being early lung adenocarcinomas with mixed in situ and invasive growth, represent those that are highly valuable in advancing our understanding of this process. All Noguchi Type C adenocarcinomas (n = 110) from the LATTICE-A cohort were reviewed and two patterns of in situ tumor growth were identified: those deemed likely to represent a true shift from precursor in situ to invasive disease ('Noguchi C1') and those in which the lepidic component appeared to represent outgrowth of the invasive tumor along existing airspaces ('Noguchi C2'). Overall Ki67 fraction was greater in C2 tumors and only C1 tumors showed significant increasing Ki67 from in situ to invasive disease. P53 positivity was acquired from in situ to invasive disease in C1 tumors but both components were positive in C2 tumors. Likewise, vimentin expression was increased from in situ to invasive tumor in C1 tumors only. Targeted next generation sequencing of 18 C1 tumors identified four mutations private to the invasive regions, including two in TP53, while 6 C2 tumors showed no private mutations. In the full LATTICe-A cohort, Ki67 fraction classified as either less than or greater than 10% within the in situ component of lung adenocarcinoma was identified as a strong predictor of patient outcome. This supports the proposition that tumors of all stages that have 'high grade' in situ components represent those with aggressive lepidic growth of the invasive clone. Overall these data support that the combined growth of Noguchi C tumors can represent two differing biological states and that 'Noguchi C1' tumors represent the genuine biological shift from in situ to invasive disease.

更新日期：2019-05-16

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