A grading system combining architectural features and mitotic count predicts recurrence in stage I lung adenocarcinoma Journal Article


Authors: Kadota, K.; Suzuki, K.; Kachala, S. S.; Zabor, E. C.; Sima, C. S.; Moreira, A. L.; Yoshizawa, A.; Riely, G. J.; Rusch, V. W.; Adusumilli, P. S.; Travis, W. D.
Article Title: A grading system combining architectural features and mitotic count predicts recurrence in stage I lung adenocarcinoma
Abstract: The International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) has recently proposed a new lung adenocarcinoma classification. We investigated whether nuclear features can stratify prognostic subsets. Slides of 485 stage I lung adenocarcinoma patients were reviewed. We evaluated nuclear diameter, nuclear atypia, nuclear/cytoplasmic ratio, chromatin pattern, prominence of nucleoli, intranuclear inclusions, mitotic count/10 high-power fields (HPFs) or 2.4 mm 2, and atypical mitoses. Tumors were classified into histologic subtypes according to the IASLC/ATS/ERS classification and grouped by architectural grade into low (adenocarcinoma in situ, minimally invasive adenocarcinoma, or lepidic predominant), intermediate (papillary or acinar), and high (micropapillary or solid). Log-rank tests and Cox regression models evaluated the ability of clinicopathologic factors to predict recurrence-free probability. In univariate analyses, nuclear diameter (P=0.007), nuclear atypia (P=0.006), mitotic count (P<0.001), and atypical mitoses (P<0.001) were significant predictors of recurrence. The recurrence-free probability of patients with high mitotic count (≥5/10 HPF: n=175) was the lowest (5-year recurrence-free probability=73%), followed by intermediate (2-4/10 HPF: n=106, 80%), and low (0-1/10 HPF: n=204, 91%, P<0.001). Combined architectural/mitotic grading system stratified patient outcomes (P<0.001): low grade (low architectural grade with any mitotic count and intermediate architectural grade with low mitotic count: n=201, 5-year recurrence-free probability=92%), intermediate grade (intermediate architectural grade with intermediate-high mitotic counts: n=206, 78%), and high grade (high architectural grade with any mitotic count: n=78, 68%). The advantage of adding mitotic count to architectural grade is in stratifying patients with intermediate architectural grade into two prognostically distinct categories (P=0.001). After adjusting for clinicopathologic factors including sex, stage, pleural/lymphovascular invasion, and necrosis, mitotic count was not an independent predictor of recurrence (P=0.178). However, patients with the high architectural/mitotic grade remained at significantly increased risk of recurrence (high vs low: P=0.005) after adjusting for clinical factors. We proposed this combined architectural/mitotic grade for lung adenocarcinoma as a practical method that can be applied in routine practice. © 2012 USCAP, Inc. All rights reserved.
Keywords: adult; controlled study; human tissue; aged; middle aged; major clinical study; histopathology; review; cancer recurrence; cancer patient; recurrence risk; neoplasm staging; cancer grading; adenocarcinoma; mitosis; ki-67 antigen; neoplasm recurrence, local; lung neoplasms; tumor markers, biological; recurrence; high risk patient; risk assessment; cancer invasion; disease severity; lung adenocarcinoma; early cancer; carcinoma in situ; cell size; cell nucleus; cell shape; cancer classification; papillary carcinoma; gender; predictive value; tissue structure; tumor necrosis; mitosis index; histologic subtype; cancer prognosis; architectural grade
Journal Title: Modern Pathology
Volume: 25
Issue: 8
ISSN: 0893-3952
Publisher: Nature Publishing Group  
Date Published: 2012-08-01
Start Page: 1117
End Page: 1127
Language: English
DOI: 10.1038/modpathol.2012.58
PROVIDER: scopus
PUBMED: 22499226
PMCID: PMC4382749
DOI/URL:
Notes: --- - "Export Date: 4 September 2012" - "CODEN: MODPE" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Camelia S Sima
    204 Sima
  2. Valerie W Rusch
    657 Rusch
  3. Andre L Moreira
    171 Moreira
  4. Emily Craig Zabor
    131 Zabor
  5. William D Travis
    552 Travis
  6. Gregory J Riely
    350 Riely
  7. Kei Suzuki
    28 Suzuki
  8. Stefan S Kachala
    10 Kachala
  9. Kyuichi Kadota
    82 Kadota