Research Papers:

Histologic subtyping in pathologic stage I-IIA lung adenocarcinoma provides risk-based stratification for surveillance

Yusuke Takahashi, Takashi Eguchi, Koji Kameda, Shaohua Lu, Raj G. Vaghjiani, Kay See Tan, William D. Travis, David R. Jones and Prasad S. Adusumilli _

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Oncotarget. 2018; 9:35742-35751. https://doi.org/10.18632/oncotarget.26285

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Yusuke Takahashi1,2, Takashi Eguchi1,3, Koji Kameda1,4, Shaohua Lu5,6, Raj G. Vaghjiani1, Kay See Tan7, William D. Travis5, David R. Jones1 and Prasad S. Adusumilli1,8

1Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA

2Department of General Thoracic Surgery, Keio University School of Medicine, Tokyo, Japan

3Division of Thoracic Surgery, Department of Surgery, Shinshu University, Matsumoto, Japan

4Department of Thoracic Surgery, National Defense Medical College, Tokorozawa, Japan

5Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

6Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China

7Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

8Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Correspondence to:

Prasad S. Adusumilli, email: [email protected]

Keywords: recurrence hazard; dynamics; solid; micropapillary; prognosis

Received: August 07, 2018     Accepted: October 21, 2018     Published: November 06, 2018


Background: We hypothesize that recurrence hazard following resection for stage I-IIA lung adenocarcinoma (ADC) varies according to histologic subtype, which may provide risk stratification for surveillance better than the current uniform follow-up protocol.

Results: Presence (≥5%) of high-grade histologic subtypes (MIP and/or SOL) was associated with a significantly higher recurrence hazard: (1) presence of either MIP or SOL was associated with a significant increase in recurrence hazard during the first two years after surgery; (2) presence of SOL was associated with an increase in recurrence hazard—in particular, distant recurrence hazard—during the first year after surgery; (3) absence of high-grade subtypes (515/1,572 patients) was associated with a very low recurrence hazard (<2% risk/year) during the first ten years after surgery.

Methods: All hematoxylin and eosin–stained tumor slides from pathologic stage I-IIA lung ADC (n = 1572) were reviewed for quantification of the percentage of each histological subtype. Recurrence hazard was estimated using the Kernel-Epanechnikov smoothing procedure. The association between recurrence hazard and high-grade histologic subtypes (micropapillary [MIP] and solid [SOL]) was assessed.

Conclusions: Our findings suggest that histologic subtyping has utility for identifying recurrence hazard for surgically resected stage I-IIA lung ADC patients and provide rationale for establishing risk-based surveillance.

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