Comprehensive Pathological Analyses in Lung Squamous Cell Carcinoma: Single Cell Invasion, Nuclear Diameter, and Tumor Budding Are Independent Prognostic.

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Comprehensive Pathological Analyses in Lung Squamous Cell Carcinoma: Single Cell Invasion, Nuclear Diameter, and Tumor Budding Are Independent Prognostic Factors for Worse Outcomes Kyuichi Kadota, MD, PhD, Jun-ichi Nitadori, MD, PhD, Kaitlin M. Woo, MS, Camelia S. Sima, MD, MS, David J. Finley, MD, Valerie W. Rusch, MD, Prasad S. Adusumilli, MD, FACS, FCCP, William D. Travis, MD Journal of Thoracic Oncology Volume 9, Issue 8, Pages 1126-1139 (August 2014) DOI: 10.1097/JTO.0000000000000253 Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 Histologic subtypes (hematoxylin and eosin-stain; original magnification, x200: A–D). A, keratinizing subtype with layered keratin. (B) Keratinizing subtype with cytoplasmic keratinization. (C) Nonkeratinizing subtype. (D) Basaloid subtype. Journal of Thoracic Oncology 2014 9, 1126-1139DOI: (10.1097/JTO.0000000000000253) Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Tumor budding and single cell invasion (hematoxylin and eosin-stain; original magnification, ×40: A, ×400: C–D). A, Tumor budding identified in invasive tumor edge. (B) Higher magnification of a square box in the Figure 3A showing tumor budding composed of less than five tumor cells (arrows). (C) Single cell invasion of tumor cells in stroma (arrows). (D) Large nuclei defined as greater than four small lymphocytes in diameter. Journal of Thoracic Oncology 2014 9, 1126-1139DOI: (10.1097/JTO.0000000000000253) Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 Overall survival (OS) by pathological stage, pleural invasion, and lymphovascular invasion. A, The 5-year OS was the worst for patients with stage III disease, followed by patients with stage II and stage I disease (40%, 51%, and 67%, respectively; p < 0.001). (B) The 5-year OS of patients with pleural invasion was significantly worse (n = 80; 42%) than those without pleural invasion (n = 405; 62%; p = 0.002). (C) The 5-year OS of patients with lymphovascular invasion was significantly worse (n = 332; 53%) than those without lymphovascular invasion (n = 153; 71%; p = 0.031). Journal of Thoracic Oncology 2014 9, 1126-1139DOI: (10.1097/JTO.0000000000000253) Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 4 Overall survival (OS) by tumor budding and single cell invasion. A, The 5-year OS of patients with high grade (≥10 buds/one high-power fields [HPF]) for maximum budding was significantly worse (n = 76; 39%) than those with low grade (<10 buds/one HPF; n = 409; 62%; p < 0.001). (B) The 5-year OS of patients with high grade (greater than or equal to eight buds/10 HPFs) for total tumor budding was significantly worse (n = 181; 46%) than those with low grade (less than eight buds/10 HPFs; n = 304; 67%; p = 0.007). (C) The 5-year OS of patients with single cell invasion in entire tumor was significantly worse (n = 197; 47%) than those without single cell invasion (n = 288; 67%; p = 0.002). (D) The 5-year OS of patients with single cell invasion in tumor edge was significantly worse (n = 134; 42%) than those without single cell invasion (n = 351; 65%; p = 0.001). Journal of Thoracic Oncology 2014 9, 1126-1139DOI: (10.1097/JTO.0000000000000253) Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 5 Overall survival (OS) by nuclear diameter. The 5-year OS of patients with large nuclei (greater than four small lymphocytes) was significantly worse (n = 153; 50%) than those with small nuclei (n = 332; 63%; p = 0.011). Journal of Thoracic Oncology 2014 9, 1126-1139DOI: (10.1097/JTO.0000000000000253) Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions