Novel Histologic Categorization Based on Lauren Histotypes Conveys Prognostic Information for Gastroesophageal Junction Cancers-Analysis from a Large Single Center Cohort in Germany

Abstract

Adenocarcinoma of the gastroesophageal junction (AEG) ranks among the most common cancers in the Western world with increasing incidence. However, the prognostic influence and applicability of the Lauren classification was not examined in detail before. The purpose of this analysis was to analyze the oncologic outcomes of GE-junction cancer related to the Lauren histotype in a large single center cohort. Data from the prospectively documented database of the Klinikum Rechts der Isar (TUM School of Medicine) for patients undergoing curatively intended oncologic resection for GE-junction cancer between 1984 and 2018 were extracted. Univariate and multivariate regression analyses were performed to identify predictors for overall survival. Kaplan-Meier analyses were done to investigate the survival rates according to the Lauren histotype. After identification of two distinct histologic categories with prognostic implications, propensity score matching (PSM) was performed to balance for confounders and evaluate its oncologic outcomes retrospectively. In the time period indicated, 1710 patients were treated for GE-junction cancer. Exclusion criteria were: R2-resections (n = 134), metastatic disease (n = 296), 30-day mortality (n = 45), Siewert type I (n = 21), and missing/incomplete data (n = 61). Finally, 1153 patients were analyzed. In a multiple variable analysis, age, UICC-stage, all Lauren histotypes, R-stage, and postoperative complications were significant predictors of overall survival. Kaplan Meier analysis demonstrated significant survival differences between intestinal, diffuse, and mixed Lauren-histotypes (p = 0.001 and p = 0.029). Survival rates were comparable between non-classifiable and intestinal Lauren-types (p = 0.16) and between diffuse and mixed types (p = 0.56). When combining non-classifiable, well, and moderately differentiated Lauren-types and combining poorly differentiated intestinal, diffuse, and mixed types, two highly prognostic groups were identified (p < 0.0001). This was confirmed after PSM for possible confounders. The Lauren histotypes demonstrate highly prognostic value after oncologic resection of GE-junction cancer (Siewert type II and type III) in a single center Western patient cohort. A simplified histotype classification based on Lauren subtypes revealed a clear distinction of prognostic groups and should be considered for further evaluation.

Keywords: Lauren histotype; gastric/gastroesophageal cancer; perioperative chemotherapy.

Figure 1

Survival curves for Lauren subtypes. HR 1.0 vs. HR 1.02, CI95% 0.69–1.51, p = 0.93 for non-classifiable vs. intestinal G1 type, HR 1.02, CI95% 0.69–1.51 vs. HR 1.04, CI95% 0.80–1.35, p = 0.92 for intestinal G1 type vs. intestinal G2 types. HR 1.43, CI95% 1.10–1.86 vs. HR 1.68, CI95% 1.27–2.23, p = 0.18. G3 intestinal vs. diffuse and HR 1.68, CI95% 1.27–2.23 vs. HR 1.55, CI95% 1.14–2.11, p = 0.56, diffuse vs. mixed types.

Figure 2

Survival curves for differentiated/undifferentiated subtypes after propensity score matching (PSM). Differentiated type (unclassifiable Lauren type, Lauren intestinal type G1 and G2) vs. Undifferentiated type (Lauren intestinal type, diffuse type, and mixed type). HR 1.31, CI95% 1.11–1.54, p = 0.002.

Figure 3

Survival curves for differentiated/undifferentiated subtypes after propensity score matching (PSM) in UICC I stage. Survival UICC I (n = 260) for a differentiated type (unclassifiable Lauren type, Lauren intestinal type, G1 and G2) vs. undifferentiated type (Lauren intestinal type, diffuse type, and mixed type). HR 0.79, CI95% 0.5–1.27, p = 0.33.

Figure 4

Survival curves for differentiated/undifferentiated subtypes after propensity score matching (PSM) in UICC II stage. Survival UICC II (n = 291) for a differentiated type (unclassifiable Lauren type, Lauren intestinal type G1 and G2) vs. undifferentiated type (Lauren intestinal type, diffuse type, and mixed type). HR 1.00, CI95% 0.73–1.36, p = 0.996.

Figure 5

Survival curves for differentiated/undifferentiated subtypes after PSM in UICC III stage. Survival UICC III (n = 407) for a differentiated type (unclassifiable Lauren type, Lauren intestinal type G1 and G2) vs. undifferentiated type (Lauren intestinal type, diffuse type, and mixed type). HR 1.32, CI95% 1.05–1.64, p = 0.016.