The Metastatic Lymph Node Number and Ratio Are Independent Prognostic Factors in Esophageal Cancer

Hsu, Wen Hu; Hsu, Po‐Kuei; Hsieh, Chih‐Cheng; Huang, Chang‐Hung; Wu, Yu‐Chung

doi:10.1007/s11605-009-0982-8

Cited by 64 publications

(50 citation statements)

References 20 publications

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“…These results suggest that HIPK2 may be a candidate tumor suppressor associated with metastasis. The role of lymphatic metastasis in aggressive malignancies has been demonstrated in multiple studies and the occurrence of regional lymph node metastasis at an early stage is a crucial step in cancer progression (25,26). To investigate the effect of HIPK2 on cell metastasis, stable HIPK2 overexpression and empty vector cell lines were established.…”

Section: Discussionmentioning

confidence: 99%

HIPK2 inhibits cell metastasis and improves chemosensitivity in esophageal squamous cell carcinoma

Zhang

Wen

et al. 2017

Exp Ther Med

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Abstract. Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive and lethal malignancies worldwide. At present, the underlying mechanisms of ESCC development and progression are poorly understood. Previous studies have demonstrated that homeodomain-interacting protein kinase-2 (HIPK2) serves an important role in cancer biology, particularly in proliferation and metastasis. However, the role of HIPK2 in ESCC cells remains unclear. In the current study, the expression of HIPK2 in ESCC specimens, adjacent non-cancerous tissues and cell lines was assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The effects of HIPK2 on cell metastasis, epithelial-mesenchymal transition (EMT) and proliferation were studied using a Transwell assay, RT-qPCR and a Cell Counting Kit-8 assay, respectively. The results indicated that HIPK2 expression was downregulated in ESCC specimens and cell lines, and HIPK2 expression was associated with tumor invasion and lymph node metastasis. Functional studies demonstrated that HIPK2 overexpression inhibited cell metastasis and EMT. Furthermore, HIPK2 overexpression suppressed cell viability during cisplatin treatment. These results suggest that HIPK2 serves an important role in regulating metastasis and the chemosensitivity of ESCC cells, implicating the potential application of HIPK2 in ESCC therapy. IntroductionEsophageal squamous cell carcinoma (ESCC) is one of the most aggressive and lethal malignancies worldwide (1). Nutritional deficiencies, nitrosamine-rich or mycotoxin-contaminated foods and low socioeconomic status are likely to contribute to ESCC (1,2). It has been reported that heavy smoking and alcohol consumption are key environmental risk factors for ESCC (3,4). Dysphagia is the most common symptom of ESCC. Although surgery is considered to be the most effective treatment for ESCC in terms of locoregional control and long-term survival, recurrence and metastases to the liver occur in the majority of cases following complete resection, resulting in a 15-25% five-year survival rate in patients with ESCC (5). Therefore, the identification of molecular mechanisms that pinpoint biologically aggressive tumors is critical for the effective management of ESCC.Homeodomain-interacting protein kinase-2 (HIPK2) is a member of an evolutionary conserved family of serine/threonine kinases and is considered to be a tumor suppressor that modulates a number of basic cellular processes, including apoptosis, proliferation, differentiation and metastasis (6-9). It has previously been demonstrated that HIPK2 mediates apoptosis and epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells contributing to fibrosis, implying that it may be a potential target for anti-fibrosis therapy (10). HIPK2 has also been demonstrated to activate the p53 protein via direct binding and phosphorylation at serine 46 following severe DNA damage (11). Puca et al (12) demonstrated that HIPK2 is an important regulator of p53 activity in response to chemothera...

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Section: Discussionmentioning

confidence: 99%

HIPK2 inhibits cell metastasis and improves chemosensitivity in esophageal squamous cell carcinoma

Zhang

Wen

et al. 2017

Exp Ther Med

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“…However, the number of metastatic LNs was not an independent prognostic factor (RR, 0.6722, P = 0.1092). Subsequently, many studies have evaluated LNR in various malignancies, including gas tric [41,42] , esophageal [43] , pancreas [44] , breast [45,46] , and bladder cancers [47] . However, to date, there have been no formal guidelines indicating that LNR should be used as an alter native to N stage.…”

Section: Lymph Node Ratiomentioning

confidence: 99%

Impact of metastatic lymph node ratio in node-positive colorectal cancer

Noura

Ohue²,

Kano³

et al. 2010

WJGS

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Colorectal cancer (CRC) is one of the most common malignant diseases in the world. Presently, the most widely used staging system for CRC is the tumor nodes metastasis classification system, which classifies patients into prognostic groups according to the depth of the primary tumor, presence of regional lymph node (LN) metastases, and evidence of distant metastatic spread. The number of LNs with confirmed metastasis is related to the severity of the disease, but this number depends on the number of LNs retrieved, which varies depending on patient age, tumor grade, surgical extent, and tumor site. Numerous studies and a recent structured review have demonstrated associated improvements in the survival of CRC patients with increasing numbers of LNs retrieved for examination. Hence, the impact of lymph node ratio (LNR), defined as the number of metastatic LNs divided by the number of LNs retrieved, has been investigated in various malignancies, including CRC. In this editorial, we review the literature demonstrating the clinicopathological significance of LNR in CRC pati ents. Some reports have indicated the advantage of considering the LNR compared to the number of LNs retrieved and/or LN status. When the LNR is taken into consideration for survival analysis, the number of LNs retrieved and/or the LN status is not always found to be a prognostic factor. The cutoff points for LNRs were proposed in numerous studies. However, optimal thresholds for LNRs have not yet received consensus. It is still unclear whether the LNR has more prognostic validity than N stage. For all these reasons, the potential advantages of LNRs in the staging system should be investigated in large prospective data sets.

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“…An increasing ratio of PLNR was linearly associated with a worsening 5-year survival: patients with a PLNR of < 25%, 25-50%, and > 50% had a 5-year survival of 47.53, 14.6, and 8.9%, respectively. In a series of 488 patients, Hsu et al [19] described that the PLNR was a prognostic factor for OS. A PLNR of 0.20 was used as cutoff point.…”

Section: Discussionmentioning

confidence: 99%

Value of Positive Lymph Node Ratio for Predicting Postoperative Distant Metastasis and Prognosis in Esophageal Squamous Cell Carcinoma

Huang¹,

Hu²,

Pang

et al. 2015

Oncol Res Treat

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Background: The aim of this study was to investigate the relationship between positive lymph node ratio (PLNR) and postoperative distant metastasis and prognosis in esophageal squamous cell carcinoma (ESCC). Patients and Methods: 167 ESCC patients with regional lymph node metastasis, who underwent radical esophagectomy and lymphadenectomy at the Ningbo Yinzhou People's Hospital between October 2005 and December 2010, were enrolled in this study. The prognostic value of PLNR was calculated by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard model analysis. Results: After a median follow-up time of 34 months, 88 (52.7%) of the 167 patients had distant metastasis and 76 (45.5%) had died. Patients with a PLNR of less than 0.15 had a 5-year distant metastasis-free survival (DMFS) rate of 33.3% while those with a PLNR greater than 0.15 had a 5-year DMFS rate of 25.5% (log-rank test, p = 0.002). Multivariate analysis indicated that a PLNR > 0.15 was an independent poor prognostic factor for DMFS (hazard ratio (HR) 1.92, 95% confidence interval (CI) 1.21-3.05) and overall survival (OS) (HR 2.08, 95% CI 1.26-3.43). This analysis was adjusted for patient age, sex, smoking behavior, and pT stage. Conclusion: The PLNR is an independent prognostic factor for predicting postoperative distant metastasis and prognosis in ESCC, and patients with a PLNR ≤ 0.15 have better OS.

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The Metastatic Lymph Node Number and Ratio Are Independent Prognostic Factors in Esophageal Cancer

Abstract: We recommend designating both regional and nonregional lymph nodes as N nodes. MLN and MLR, but not TLN, are prognostic factors in esophageal cancer.

Cited by 64 publications

References 20 publications

HIPK2 inhibits cell metastasis and improves chemosensitivity in esophageal squamous cell carcinoma

HIPK2 inhibits cell metastasis and improves chemosensitivity in esophageal squamous cell carcinoma

Impact of metastatic lymph node ratio in node-positive colorectal cancer

Value of Positive Lymph Node Ratio for Predicting Postoperative Distant Metastasis and Prognosis in Esophageal Squamous Cell Carcinoma

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