Predictors of Lymph Node Metastasis and Differences Between Pure and Mixed Histologic Types of Early Gastric Signet-ring Cell Carcinomas

The aim of this study was to investigate predictors of lymph node metastasis (LNM) in early gastric signet-ring cell carcinoma (SRCC) and determine clinicopathologic and prognostic differences of different histologic subtypes. We retrospectively analyzed 13,661 gastric cancer patients; 231 were eligible for inclusion. Data for clinical, endoscopic, and histopathologic characteristics and prognoses were collected. Patients were followed up regarding postresection survival; overall and disease-specific survival rates were estimated by the Kaplan-Meier method with a log-rank test, and prognostic factors were evaluated by Cox regression. LNM incidence in early SRCC was 16.0% (37/231) overall: 6.9% (8/116) and 25.2% (29/115) in patients with pure and mixed SRCC, respectively. Univariate and multivariate analyses revealed SM2 invasion (odds ratio [OR] = 5.070, P = 0.003), lymphovascular invasion (LVI) (OR = 14.876, P < 0.001), pathologic pattern of mixed SRCC (OR = 3.226, P= 0.026), ulcer presence (OR = 3.340, P= 0.019) and lesion size over 20 mm (OR = 2.823, P= 0.015) as independent risk factors for LNM. Compared with pure SRCC, the mixed subtype was associated with older age, larger lesion size, higher LVI frequency, more frequent perineural invasion, and most importantly, higher LNM incidence. Patients with pure SRCC showed significantly longer overall survival (P = 0.004) and disease-specific survival (P = 0.002) than mixed SRCC patients. Pathologic subtype (hazard ratio [HR] = 3.682; P = 0.047), age (HR = 5.246; P=0.001), SM1 invasion (HR = 6.192; P = 0.023), SM2 invasion (HR = 7.529; P = 0.021) and LNM (HR = 5.352; P< 0.001) were independent prognostic factors. Independent risk factors for LNM in early gastric SRCC were SM2 invasion, LVI, pathologic pattern, ulcer presence and lesion size over 20 mm. Early SRCC should be further classified by the purity of the SRC component.