Prognostic implication of isolated tumor cells and micrometastases in regional lymph nodes of gastric cancer

Abstract

Aim: To determine the prognostic significance of isolated tumor cells (ITCs) and lymph node micrometastases in gastric cancer.

Methods: Hematoxylin and eosin-stained slides of lymph node dissections of 632 consecutive gastric cancers were reviewed. Cytokeratin immunostaining was performed in 280 node-negative cases and 5 cases indefinite for lymph node metastases. Lymph node metastases were divided into ITCs, micrometastases, or macrometastases, according to the sizes of tumor deposits in largest dimension. ITCs were further classified into four groups according to metastasis pattern.

Results: Lymph node metastases were identified by immunostaining in 58 of 280 node-negative cases (20.7%) and were not significantly associated with patient survival (P = 0.3460). After cytokeratin immunostaining, 196 cases were classified as pN1, which consisted of 20 cases with micrometastases detected by immunostaining (pN1mi(i+)), 34 cases with only micrometastases (pN1mi), and 142 cases with pN1 with one or more macrometastases (pN1). Cases with pN1mi and pN1mi(i+) had a significantly better prognosis than the cases with pN1 (P = 0.0037). ITCs were found in 38 of these 58 cases, and could be divided into four groups: 12 cases with only a single cell pattern, 7 cases with multiple individual cells, 5 cases with single small cluster, and 14 cases with multiple small clusters. Among these four groups, cases with ITCs of multiple individual cell pattern showed the worst survival (median survival: 28 mo, P<0.0001).

Conclusion: Both size and pattern of lymph node metastases can give prognostic information on the survival of gastric cancer patients.

Figure 1

Immunohistochemical staining against cytokeratin. A: Single cell only (×400); B: single small cluster (×400); C: multiple small clusters (×200); D: multiple individual cells (×400); E: HE-stained slides of multiple individual tumor cells in lymph nodes (the same area of D, ×400); F: micrometastasis (×400).

Figure 2

Survival curves using the Kaplan-Meier method. A: Patient survival according to reclassified pN stage; B: survival curve of cases with pN1 with one or more macrometastases, pN1mi, and pN1mi(i+); C: survival curve of the cases with pN0 stage, pN1mi(i+), pN1mi, and pN1; D: prognostic impact of lymph node metastases as detected by immunostaining; E: survival curves according to the pattern of ITCs; F: survival curves according to the pattern of ITCs deleting patients with stage IV disease; G: survival curves according to the number of positive nodes.