Abstract
BackgroundExtra-capsular growth (ECG) describes the extension of neoplastic cells beyond the lymph node capsule. Aim of this study was to investigate the prognostic value of ECG and its association with a stem cell like phenotype indicated by expression of the transcription factor SOX9 in gastric cancer.MethodsBy histological evaluation, 199 patients with nodal positive gastric cancer or adeoncarcinoma of the esophageal-gastric junction (AEG) were divided into two groups according to the presence (ECG) or absence (ICG) of extracapsular growth in at least one nodal metastasis. Of these, 194 patients were stained for SOX9 and SOX2 using immunohistochemistry. Seventeen nodal negative patients (pT3/4, pN0, pM0) served as controls.ResultsSeventy-three patients (36.7%) showed ECG. ECG was associated with lower overall survival (p < 0.0001), advanced pT- (p = 0.03) and pN- category (p < 0.0001) and lymphovascular invasion (p = 0.014). In multivariate analysis, ECG was found to be an independent prognostic factor (HR = 2.1; 95% CI 1.7–3.4; p = 0.001). SOX9 expression correlated significantly with ECG (96% SOX9 high in ECG patients vs. 79% SOX9 high in patients with ICG; p = 0.002). Controls showed significantly reduced SOX9 expression compared to nodal positive carcinomas (59% vs. 85% high SOX9 expression; p = 0.006). No significant correlation of ECG and SOX2 (59% SOX2 negative in ECG patients vs. 64% in patients with ICG, p = 0.48) could be obtained.ConclusionsPatients with ECG exhibit poorer prognosis and ECG was found to be an independent prognostic factor. Thus, ECG turns out to be a morphological biomarker for a more aggressive phenotype in gastric cancer. This is supported by the fact that ECG correlates with the expression of SOX9, which has been described in the context of pro-oncogenic properties of tumours. However, the fact that SOX2 failed to show significant results indicate that ECG is not associated with a distinct cancer stem cell phenotype in gastric cancer.
Highlights
Extra-capsular growth (ECG) describes the extension of neoplastic cells beyond the lymph node capsule
Patients with extra-capsular growth (ECG) had a median survival of 16. 21 months (95% confidence interval (CI) 11.69–20.74; standard deviation (SD) 2.31) whereas patients without ECG had a median survival of 37.07 months
We could not proof a correlation of EGC with a distinct stem cell phenotype. It could be concluded from our data that SOX9 acts as a pro-oncogene in gastric cancer and plays an important role in gastric cancer progression and formation of ECG in lymph node metastasis
Summary
Extra-capsular growth (ECG) describes the extension of neoplastic cells beyond the lymph node capsule. The extra-capsular growth (ECG) describes the extension of neoplastic cells beyond the lymph node capsule into the perinodular soft tissue. Being a prognostic factor for cancer in several organs [1, 2] including the gastrointestinal tract [3, 4], ECG has already found access to. The parameter ECG is suggested to be included as a prognostic parameter in colorectal cancer staging systems [6]. ECG is associated with poorer 5-year survival and was found to be an independent prognostic factor [4, 7]. ECG is associated with larger tumour size, advanced pT- and pN-category and lymphovascular and perineural invasion [4, 7].
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