Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Aug;25(8):1117-27.
doi: 10.1038/modpathol.2012.58. Epub 2012 Apr 13.

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

Kyuichi Kadota  1 , Kei Suzuki, Stefan S Kachala, Emily C Zabor, Camelia S Sima, Andre L Moreira, Akihiko Yoshizawa, Gregory J Riely, Valerie W Rusch, Prasad S Adusumilli, William D Travis
Affiliations

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

Kyuichi Kadota et al. Mod Pathol. 2012 Aug.

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest disclosures

All authors affirm that we have no actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations.

Figures

Figure 1
Figure 1. Nuclear features of lung adenocarcinoma (hematoxylin and eosin stain; original magnification, ×400: A–E, ×600: F)
(A) Tumor cells showing mild nuclear atypia with small nuclei, intermediate nuclear/cytoplasmic (N/C) ratio, fine granular chromatin, and distinct nucleoli. (B) Tumor cells showing moderate nuclear atypia with intermediate size nuclei, and low N/C ratio. (C) Tumor cells showing large nuclei with atypical mitosis (arrow). (D) Tumor cells showing severe nuclear atypia with coarse granular chromatin, and large nucleoli. (E) Tumor cells showing high N/C ratio, homogeneous chromatin, and indistinct nucleoli. (F) Tumor cells with intranuclear inclusion (arrow).
Figure 2
Figure 2. Recurrence- free probability (RFP) by mitotic count and architectural grade
(A) The recurrence-free probability of patients with high mitotic count (n=175) was the lowest (5-year recurrence-free probability=73%), followed by intermediate (n=106, 80%), and low (n=204, 91%). (B) The recurrence-free probability of patients with high architectural grade (n=78) was the lowest (68%), followed by intermediate (n=371, 84%), and low (n=36, 92%). (C) Within the intermediate architectural grade, patients with low mitotic count (n=165) had higher 5-year recurrence-free probability (92%) compared to the intermediate (n=91, 77%) – high mitotic count (n=115, 79%). (D) Within the high architectural grade, patients with high mitotic count (n=58) had lower 5-year recurrence-free probability (60%) compared to the low (n=7, 86%) – intermediate mitotic count (n=13, 100%).
Figure 3
Figure 3. Overall grade grouping based on recurrence-free probability (RFP) by architectural grade and mitotic count
Low architectural/mitotic grade: low architectural grade with any mitotic count (5-year recurrence-free probability=91–100%) and intermediate architectural grade with low mitotic count (92%). Intermediate architectural/mitotic grade: intermediate architectural grade with intermediate-high mitotic count (77–79%). High architectural/mitotic grade: high architectural grade with any mitotic count (60–100%).
Figure 4
Figure 4. Recurrence-free probability (RFP) by architectural/mitotic grading system
Patients with the high architectural/mitotic grade (n=78) had the lowest 5-year recurrence-free probability (68%), followed by intermediate (n=206, 78%) and low (n=201, 92%).
See this image and copyright information in PMC

References

    1. Devesa SS, Bray F, Vizcaino AP, Parkin DM. International lung cancer trends by histologic type: male:female differences diminishing and adenocarcinoma rates rising. Int J Cancer. 2005;117:294–9. - PubMed
    1. Motoi N, Szoke J, Riely GJ, et al. Lung adenocarcinoma: modification of the 2004 WHO mixed subtype to include the major histologic subtype suggests correlations between papillary and micropapillary adenocarcinoma subtypes, EGFR mutations and gene expression analysis. Am J Surg Pathol. 2008;32:810–27. - PubMed
    1. Okudela K, Woo T, Mitsui H, et al. Morphometric profiling of lung cancers. Its association with clinicopathologic, biologic, and molecular genetic features. Am J Surg Pathol. 2010;34:243–55. - PubMed
    1. Sica G, Yoshizawa A, Sima CS, et al. A grading system of lung adenocarcinomas based on histologic pattern is predictive of disease recurrence in stage I tumors. Am J Surg Pathol. 2010;34(8):1155–62. - PubMed
    1. Barletta JA, Yeap BY, Chirieac LR. Prognostic significance of grading in lung adenocarcinoma. Cancer. 2010;116(3):659–69. - PMC - PubMed

Publication types