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O17 - Anatomical Pathology I (ID 128)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Pathology
- Presentations: 1
O17.06 - Tumor Budding and Nuclear Grade, but not Histologic Subtype, Are Significant Prognostic Factors, Independent of TNM Stage, in Patients with Lung Squamous Cell Carcinoma (ID 2910)
10:30 - 12:00 | Author(s): D.J. Finley
The new IASLC/ATS/ERS lung adenocarcinoma classification, proposed in 2011, has significant prognostic value. For lung squamous cell carcinoma (SCC), however, no pathologic findings have been widely accepted to predict patient outcomes with the exception of TNM stage. Tumor budding has been recognized as a factor of poor prognosis in colorectal cancer, and nuclear grading has been widely accepted as a prognostic indicator in breast cancer. In this study, we determine whether histologic findings can independently predict prognosis in lung SCC.
All available tumor slides from patients with therapy-naive, surgically resected solitary lung SCC (1999-2009) were reviewed (n=485; stage I/II/III, 281/136/68). Tumors were graded by means of tumor differentiation. Tumors were classified as keratinizing, nonkeratinizing, and basaloid subtypes by presence (≥5%) or absence of keratinization and by predominant (≥50%) basaloid pattern. Tumor budding (tumor nests composed of <5 cells) and presence of single tumor-cell invasion were assessed using 10 high-power fields (HPFs) (x200 magnification) in the areas with the smallest tumor nests. Tumor budding was considered positive when the maximum number of budding was ≥10/HPF. Single tumor-cell invasion was considered positive when it was identified at 10 HPFs. Nuclear diameter was evaluated, at ≥3 HPFs in the largest nuclei, using nearby small lymphocytes as reference and was classified as either large (>4 small lymphocytes) or small (≤4). Overall survival (OS) was estimated using the Kaplan-Meier method, and multivariate analyses were performed using the Cox proportional hazards model.
Basaloid subtype correlated with better OS than nonbasaloid subtype (p=0.046). Tumor budding (p<0.001), single tumor-cell invasion (p<0.001), and large nuclei (p=0.005) correlated with worse OS (Table). However, tumor differentiation and presence of keratinization did not correlate with prognosis. The prognostic significance of tumor budding was confirmed in a subgroup analysis limited to stage I (p=0.028) and stage II/III (p=0.008) patients. In addition, basaloid subtype correlated with favorable prognosis (p=0.042), and both single tumor-cell invasion (p=0.014) and large nuclei (p=0.021) were associated with poor prognosis in a subgroup analysis limited to stage I patients. In multivariate analysis, tumor budding (HR=1.04; p=0.024) and large nuclei (HR=1.09; p=0.035) were independent prognostic factors for survival.
Table. Overall survival by histologic findings
Histologic finding 5-year OS p Subtype Basaloid 69% (n=33) 0.046 Nonbasaloid 58% (n=452) Tumor budding + 39% (n=76) <0.001 - 62% (n=409) Single cell invasion + 47% (n=197) <0.001 - 67% (n=288) Nuclei Large 50% (n=153) 0.005 Small 63% (n=332)
Tumor budding and large nuclei, but not histologic subtype, were significant prognostic factors, independent of TNM stage, for lung SCC. These findings may help to make therapeutic decisions and stratify patients for additional therapy.
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