Evaluation of immune response according to the metastatic status in the regional lymph nodes in patients with gastric carcinoma

Abstract

Abstract. The immunological response in the regional lymph nodes (LN) of gastric cancer patients who had metastasis was studied by investigating both the degree of metastasis and the maturation status of dendritic cells (DCs). A total of 732 LNs was obtained from 29 gastric cancer patients, including 25 patients whose LNs were pathological metastasis-negative and 4 patients with metastasis-positive LNs. Micrometastasis (MM) in the LNs was analyzed by immunohistochemical staining of cytokeratin (CK) (IHC-MM) and by amplifying CEA and CK19 mRNA by quantitative real-time RT-PCR (PCR-MM). Distribution and density of mature DCs were evaluated in 119 LNs from pathological metastasis-positive cases by examining CD83 expression immunohistochemically. Then, following the examination of PCR-MM, immunological responses were analyzed by amplifying CD83, CD86, CD1a and IFNÁ mRNA by quantitative real-time RT-PCR in 613 LNs from 25 pathological metastasis-negative cases. Among 119 LNs from 4 patients with LN metastasis, 20 LNs had histological metastasis and 6 histological metastasis-negative LNs had IHC-MM. The distribution and density of mature DCs were identical in the LNs regardless of metastasis status. Among 613 LNs from 25 patients without histological LN metastasis, 15 LNs (2.45%) from 6 cases (24%) were PCR-MM positive. The expression levels of CD83 and CD86 mRNA were significantly higher in the 15 PCR-MM-positive LNs than in the 598 PCR-MMnegative LNs. The expression levels of CD83 and CD86 mRNA in 136 PCR-MM-negative LNs from 6 PCR-MMpositive cases were also higher than those in 462 LNs from 19 PCR-MM-negative cases. In gastric cancer patients, activation of the immune response by maturation of DCs is wide-spread in regional lymph nodes at a stage before metastasis is detected histologically, including detection by IHC-MM.

Occult Tumor Cells in Lymph Nodes of Patients with Gastric Cancer: A Systematic Review on Their Prevalence and Predictive Role

“…The majority of the studies (n = 18) did not evaluate the association between LN OTC presence and survival, or were inconclusive in this respect [3,5,6,10,11,23,25,26,27,28,31,36,38,40,45,46,47] (table 3). Several articles (n = 16) reported that OTC were associated with worse prognosis [1,2,7,12,13,14,16,17,19,22,29,33,35,39,41,43] (table 4), while in some (n = 8) such an association was not found [4,15,18,20,21,32,34,44] (table 5).…”

“…With PCR/RT-PCR methods, the variability of markers was greater than with IHC, the carcinoembryonic antigen (CEA) being the most frequently used (n = 7) [5,10,27,31,34,44,47]. …”

“…The majority of the studies (n = 27) [2,3,4,6,10,12,13,15,18,20,21,22,23,24,25,27,28,29,31,34,38,39,41,42,43,44,45] included only N0 patients and reported an OTC detection rate from 0.4 [28] to 28.6% [16]. It was reported that patients classified as ≥N1 had a higher prevalence of MM.…”

“…The case-control study [4] included 40 cases, defined as patients who presented locoregional or distant recurrence, and 41 controls. The sample size varied from 25 [10] to 355 [11] subjects, with a median age between 53 and 67 years and a predominance of male gender (54 [12] to 92% [13]). The study duration varied between 1 [2,14] and 23 years [15].…”

CD169 identifies an activated CD8+T cell subset in regional lymph nodes that predicts favorable prognosis in colorectal cancer patients

“…16,17 Despite the presence of CD8 C T cells in the primary tumor, a lower percentage of effector CD8 C T cells has also been found in the metastatic or pre-metastatic LN of CRC patients, suggesting that cell-mediated immunity also depends on the localization and functional role of CD8 C T cells in the tumor-draining LN. 18,19 Thus, defining the potential CD8 C T cell subsets in LNs is essential to understanding their roles and mechanisms in tumor immunopathogenesis. CD169, also known as sialoadhesin or sialic acid binding immunoglobulin-like lectin, is the founding member of the Siglec superfamily.…”