Lymph Node Micrometastasis In Gastric Cancer Research Articles

Abstract 3466: Prognostic implications of lymph node micrometastasis in patients with gastric cancer

Abstract Purpose: The clinical significance of lymph node micrometastasis (LNMM) remains controversial in gastric cancer (GC). In this study, we investigated the prognostic impact of patients with LNMM GC.Methods: A total of 624 patients with pathologically lymph node metastasis negative (pN0) and N1 status (pN1) who underwent gastrectomy between 2004 and 2018 were enrolled in this retrospective study. The diameter of tumor cell clusters in metastatic lymph nodes was measured in 120 patients with pN1 GC. Results: Patients with lymph node tumors of diameter < 1500 μm (LNMM) had significantly better prognosis than those with tumors of diameter ≥ 1500 μm (p = 0.012; log-rank test). Cox’s proportional hazards model revealed that LNMM (p = 0.016), several dissected lymph nodes (p = 0.049), and the provision of adjuvant chemotherapy (p = 0.002) were independent prognostic factors for overall survival of patients with pN1 GC. There was no significant difference in overall survival between patients with LNMM who received chemotherapy and those who did not (p = 0.332). Conclusions: LNMM is associated with favorable prognosis and could be an independent prognostic marker in patients with pN1 GC. LNMM in GC may be considered as one of the factors preventing adjuvant chemotherapy. Citation Format: Atsushi Yamamoto, Hirotaka Okamoto. Prognostic implications of lymph node micrometastasis in patients with gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3466.

Prognostic impact of lymph node micrometastasis in patients with gastric cancer.

The clinical significance of lymph node micrometastasis (LNMM) remains controversial in gastric cancer (GC). In this study, we investigated the prognostic impact of LNMM in patients with GC. A total of 624 patients with pathologically lymph node metastasis-negative (pN0) and N1 status (pN1) who underwent gastrectomy between 2004 and 2018 were enrolled in this retrospective study. The diameter of tumor cell clusters in metastatic lymph nodes was measured in 120 patients with pN1 GC. Patients with lymph node tumors < 1500μm in diameter (LNMM) had a significantly better prognosis than those with tumors ≥ 1500μm in diameter (p = 0.012; log-rank test). Cox's proportional hazards model revealed that LNMM (p = 0.016), several dissected lymph nodes (p = 0.049), and the provision of adjuvant chemotherapy (p = 0.002) were independent prognostic factors for the overall survival of patients with pN1 GC. There was no significant difference in the overall survival between patients with LNMM who received chemotherapy and those who did not (p = 0.332). LNMM is associated with a favorable prognosis and maybe an independent prognostic marker in patients with pN1 GC. LNMM in GC may be considered a factor preventing adjuvant chemotherapy.

Current status of lymph node micrometastasis in gastric cancer.

Lymph node metastasis is one of the most important prognostic factors in patients with gastric cancer. An inadequate number of dissected lymph nodes is an independent risk factor affecting recurrence, even in patients who are node negative. Oddly, certain early-stage patients still experience recurrence or metastasis within a short time, even if they have undergone standard radical mastectomy. Many researchers have attributed these adverse events to lymph node micrometastasis (LNM), which is defined as a microscopic deposit of malignant cells of less than 2 mm in diameter. With the development of diagnostic tools such as immunohistochemistry and reverse transcription-polymerase chain reaction, the rate of detection of LNM has been constantly increasing. Although there is no clear consensus about risk factors for or the definitive clinical significance of LNM, the clinical impact of LNM is remarkable in gastric cancer. For minimally invasive treatment in particular, such as endoscopic submucosal dissection and laparoscopic surgery, accurate diagnosis of LNM is regarded as the potential key to maintaining the balance between curability and safety. This review provides an overview of the definition, detection and significance of LNM in gastric cancer. We also summarize several attention-drawing controversies regarding the treatment of patients who may have LNM.

Cadherin-17 induces tumorigenesis and lymphatic metastasis in gastric cancer through activation of NFκB signaling pathway

Cadherin-17 (CDH17), as a structurally unique member of the cadherin superfamily, has been identified to predict a poor prognosis for gastric cancer (GC). Our previous study demonstrated the positive correlation between CDH17 and lymph node micrometastasis in GC. We sought to further identify the role of CDH17 in the tumorigenesis and lymphatic metastasis of GC. Hence, we inhibited the CDH17 expression in MKN-45 gastric cancer cells by using RNA interference. Consequently, the malignant potency of cancer cells was evaluated, and the change in NFκB signaling pathway was also probed. Tumor growth and lymphatic metastasis model were conducted in nude mice to confirm the hypothesis. Downregulation of CDH17 not only suppressed the proliferation, adherence and invasion potency of MKN-45 cells, but also induced cell cycle arrest. Meanwhile, the NFκB signaling pathway was inactivated as well, with the reductions of downstream proteins including VEGF-C and MMP-9. Moreover, silencing CDH17 inhibited tumor growth in vivo significantly, and there was no lymph node metastasis detected in the mice without CDH17 expression, as opposed to the positive nodes found in controls. CDH17 is a novel oncogene in gastric cancer cells, which is associated with lymphatic metastasis and proliferation strongly. The inactivation of NFκB signaling pathway might be involved in targeting CDH17 in GC. On the whole, CDH17 is proposed to serve as a biomarker and attractive therapeutic target in GC.

Clinical Significance of Lymph Node Micrometastasis in Gastric Cancer

Recently, the existence of lymph node micrometastasis (LNM), including isolated tumor cells, has been focused on during the development of molecular diagnostic tools for lymph node metastasis in various malignant neoplasms. In particular, immunohistochemistry and reverse transcription-polymerase chain reaction have been reported to be available for the detection of LNM in gastric cancer. However, at present, the clinical significance of LNM remains unclear in patients with gastric cancer. Therefore, we cannot strategically make light of this issue in clinical management. Currently, minimally invasive treatments, such as endoscopic submucosal dissection and laparoscopic surgery with personalized lymphadenectomy, are widely performed in consideration of postsurgical quality of life (QOL). However, it is important to maintain the balance between QOL and curability when selecting surgical treatments for patients with gastric cancer. If minimally invasive surgery based on LNM status was established for patients with early gastric cancer, it could be performed safely. We reviewed the clinical significance of LNM as an important strategic target in patients with gastric cancer.

Immunohistochemical Assay for Lymph-Node Micrometastasis in Gastric Cancer and Correlation with Survival Rate

Purpose: The purpose of this study is to identify immunohistochemical evidence of lymph-node micrometastasis in histologic node-negative gastric cancer patients and to evaluate the prognostic significance of lymph-node micrometastasis.Materials and Methods: A retrospective study of 50 gastric cancer patients who underwent curative resections from October 1990 to November 1994 was performed. Two consecutive sections were prepared: one for ordinary hematoxylin and eosin staining, and the other for immunohistochemical staining with Pan cytokeratin antibody (Novocastra, UK). In the univariate analysis, the survival rate was calculated using the Life Table Method, and the multivariate analysis was determined using a Cox Proportional HazardsModel. The statistical analyses of the relationships between the clinicopathologic factors and micrometastases were performed by using a Chi-square test. Results: Of 2522 harvested lymph nodes, 81 () nodes and 19 () of 50 patients were identified as having lymphnode micrometastases by using immunohistochemical staining for cytokeratin. The incidence of lymph-node micrometastases was significantly higher in diffuse type carcinomas (, P=0.024) and in patients with serosal invasion (, P=0.05). For patients with lymph-node micrometastases (n=19), the 5-year survival rate was significantly decreased (, P=0.015). The Lauren's classirication (P=0.021) and the depth of invasion (P=0.035) were shown by multivariate analysis to have a significant relationship with the presence of micrometastases. Multivariate analysis revealed that lymph-node micrometastasis was independently correlated with survival in histologic node-negative gastic cancer patients. Conclusion: The presence of cytokeratin detected lymphnode micrometastases correlates with the worse prognosis for patients with histologic node-negative gastric cancer.