Gastric carcinoma: stage migration by immunohistochemically detected lymph node micrometastases

Abstract

Background Immunohistochemically detected micrometastases of the regional lymph nodes in previously pN0-classified gastric cancer have been incorporated in the TNM staging system. This study aims to determine the incidence of such micrometastases in gastric carcinoma and to investigate their impact on stage grouping and prognosis. Methods Ninety-five patients with gastric carcinoma classified as pN0 by conventional histological examination were enrolled. All patients underwent gastric resection with regional lymphadenectomy between 2006 and 2010. A total of 2018 lymph nodes was obtained (median, 20 Lymph nodes) and immunohistostained with anti-pan cytokeratin antibody (KL1). Results Micrometastases were detected in regional lymph nodes by immunohistostaining in 16 out of all 95 patients. Fourteen patients were upstaged by micrometastasis-positive regional lymph nodes. Three patients demonstrated lymph nodes with isolated tumor cells alone. A significantly higher incidence of micrometastases was observed in patients with diffuse histologic type (p = 0.007) and total gastrectomy (p = 0.007). When isolated tumor cells were also regarded as lymph node involvement, the recurrence rate was significantly higher for node-positive than for node-negative patients and for those younger than 70 years (33.3 and 6.7 %, respectively; p = 0.026; n = 39). Overall survival analysis revealed no significant difference between micrometastasis-positive and micrometastasis-negative patients. ConclusionImmunohistostaining of regional lymph nodes in node-negative gastric carcinoma patients leads to an increased detection of micrometastases with significant implications for the staging system. Although no impact on survival time was shown, the higher recurrence rate for node-positive patients younger than 70 years indicates a prognostic value of immunohistochemically detectable micrometastases.

Survival benefit of greater number of lymph nodes dissection for advanced node-negative gastric cancer patients following radical gastrectomy

“…Recently, a meta-analysis of observational studies about lymph nodes micrometastases of early and advanced gastric cancer showed that there is a positive correlation between lymph nodes micrometastases and an unfavorable surgical outcome in gastric cancer patients (9). However, Theresa et al (27) had been reported that immunohistostaining of regional lymph nodes in node-negative gastric cancer patients led to an increased detection of lymph nodes micrometastases with significant implications for the staging system, but there was no impact on the survival time of these patients. Previously in vitro research indicated that some of the isolated tumor cells will be regressed spontaneously upon resection of the primary tumor owing to the activity of natural killer cells, whereas micrometastases continued to proliferate and eventually grew into gross metastases (28).…”

N staging: the role of the pathologist

“…This finding is secondary to the loss of E-cadherin expression, a critical event occurring in diffuse type gastric carcinoma (56) which, decreasing intercellular adhesion, ultimately leads to tumor cell dissociation (57). The higher probability of micrometastasis and ITC occurrence in diffuse gastric cancer (50,55,56) potentially supports the importance of lymph node immunostaining in this cancer type. Although lymph nodes harboring IHC-detected micrometastasis are considered positive nodes in gastric carcinoma, their clinical impact is unclear (58).…”

“…Various clinicopathologic parameters appear associated with the occurrence of micrometastases. IHC-detected lymph nodes micrometastases were found to be significantly more frequent in Lauren's diffuse histotype (53)(54)(55). This finding is secondary to the loss of E-cadherin expression, a critical event occurring in diffuse type gastric carcinoma (56) which, decreasing intercellular adhesion, ultimately leads to tumor cell dissociation (57).…”

Detection of Occult Lymph Node Tumor Cells in Node-Negative Gastric Cancer Patients

“…While some authors suggest micrometastasis association with tumor size, grade of histological differentiation (G2/G3) and Lauren´s diffuse histology 4 , 5 , 11 , 12 , 26 , these results didn´t find any differences in LN involvement with respect to these characteristic. However, was observed that in the CK-positive group tumor tends to be larger than in the CK-negative group (4.0 vs. 2.8 cm).…”