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01-11-2007

Lymph Node Metastasis Density and Growth Pattern as Independent Prognostic Factors in Advanced Esophageal Squamous Cell Carcinoma

Authors: Akira Ooki, Keishi Yamashita, Nobuyuki Kobayashi, Natsuya Katada, Shinichi Sakuramoto, Shiroh Kikuchi, Masahiko Watanabe

Published in: World Journal of Surgery | Issue 11/2007

Abstract

Background

Esophageal cancer is one of the leading types of cancer, and it is a particularly deadly form of malignancy. TNM classification is the most common staging system, but it has been reported that prognosis is not reflected adequately by this classification. The purpose of this study was to clarify independent prognostic factors in esophageal squamous cell carcinoma (ESCC), a dominant type of esophageal cancer in Japan, to broaden the staging system to improve its predictive value. Thus staging could be expanded to make the prognosis a valuable clinical tool, and to improve knowledge of the biological traits of advanced ESCC.

Methods

The present study included 121 patients with advanced ESCC (stage II to IVA) treated by esophagectomy between 1990 and 2003 at the Kitasato University Higashi Hospital.

Results

Univariate prognostic analysis of the disease-specific survival revealed that TNM stage (p < 0.0001), lymph node metastasis density over 10% (ND10; p < 0.0001), R-category (p = 0.003), intramural metastasis within the esophagus (IM; p = 0.009), growth pattern (p = 0.01), and size of tumor (p = 0.02) were significantly associated with a poor outcome in advanced ESCC. Multivariate analysis confirmed that growth pattern (p = 0.02, HR = 3.1) and ND10 (p = 0.02, HR = 2.0) were finally remnant prognostic factors independent of TNM stage. Growth pattern was prominent in stage II, whereas ND10 was directly proportional to stage progression and characteristics to stage IV disease. Interestingly, ND20, the most malignant phenotype of ESCC, was the only prognostic determinant, even in stage IV disease.

Conclusions

From the present study, we concluded that progression of lymph node density is characteristic of a life-threatening phenotype of advanced ESCC, and it should be employed as a therapeutic target to improve patient survival. Growth pattern is an alternative target characteristic of less advanced ESCC. Both of these parameters may be applied as useful clinical tools in the management of patients with advanced esophageal cancer.

Ferlay J, Bray F, Pisani P et al. (2001) GLOBOCAN2000: Cancer Incidence, Mortality and Prevalence Worldwide, Version 1.0. IARC Cancer Base No. 5, Lyon, France, IARC Press

Shinoda M, Hatooka S, Mori S, et al. (2006) Clinical aspects of multimodality therapy for resectable locoregional esophageal cancer. Ann Thorac Cardiovasc Surg 12(4):234–241PubMed

Schneider P, Baldus S, Metzger R, et al. (2005) Histomorphologic tumor regression and lymph node metastases determine prognosis following neoadjuvant radiochemotherapy for esophageal cancer. Ann Surg 242(5):684–692PubMedCrossRef

Union Internationale Contre Le Cancer (2002) TNM Classification of Malignant Tumours, 6th Edition, New York, Wiley-Liss

Japanese Society for Esophageal Disease. (2001) Guidelines for Clinical and Pathological studies on Carcinoma of the Esophagus, 9th Edition, Tokyo, Kanehara and Co, Ltd

Rice T, Blackstone E, Rybicki L, et al. (2003) Refining esophageal cancer staging. J Thorac Cardiovasc Surg 125(5):1103–1113PubMedCrossRef

Tachibana M, Kinugasa S, Dhar D, et al. (2001) Dukes’ classification as a useful staging system in resectable squamous cell carcinoma of the esophagus. Virchows Arch 438:350–356PubMedCrossRef

Nozoe T, Sugimachi K (2003) Simple staging criteria for esophageal carcinoma. Am J Clin Oncol 26(3):307–311PubMedCrossRef

Kuwano H, Watanabe M, Sadanaga N, et al. (1994) Univariate and multivariate analyses of the prognostic significance of discontinuous intramural metastasis in patients with esophageal cancer. J Surg Oncol 57(1):17–21PubMedCrossRef

10.

Zafirellis K, Dolan K, Fountolakis A, et al. (2002) Multivariate analysis of clinical, operative and pathologic features of esophageal cancer: who needs adjuvant therapy? Dis Esophagus 15:155–159PubMedCrossRef

11.

Siewert JR, Feith M, Werner M, et al. (2000) Adenocarcinoma based on anatomical topographical classification in 1,002 patients. Ann Surg 232:353–361CrossRef

12.

Brucher B, Stein H, Werner M, et al. (2001) Lymphatic vessel invasion is an independent prognostic factor in patients with a primary resected tumor with esophageal squamous cell carcinoma. Cancer 92:2228–2233PubMedCrossRef

13.

Roder JD, Busch R, Stein HJ, et al. (1994) Ratio of invaded to removed lymph nodes as a predictor of survival in squamous cell carcinoma of the oesophagus. Br J Surg 81:410–413PubMedCrossRef

14.

Tachibana M, Dhar DK, Kinugasa S, et al. (2000) Esophageal cancer with distant lymph node metastases: prognostic significance of metastatic lymph node ratio. J Clin Gastroenterol 31:318–322PubMedCrossRef

15.

Peto R, Pike MC, Armitage P, et al. (1977) Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples. Br J Cancer 35:1–39PubMed

16.

Cox DR (1972) Regression models and life tables. J R Stat Soc 34:1987–2001

17.

Hosch SB, Izbicki JR, Pichlmeier U, et al. (1997) Expression and prognostic significance of immunoregulatory molecules in esophageal cancer. Int J Cancer 74:582–587PubMedCrossRef

18.

Algarra I, Garcia-Lora A, Cabrera T, et al. (2004) The selection of tumor variants with altered expression of classical and nonclassical MHC class I molecules: implications for tumor immune escape. Cancer Immunol Immunother 53(10):904–910PubMedCrossRef

19.

Seliger B (2005) Strategies of tumor immune evasion. Bio Drugs 19(6):347–354

20.

Tomimaru Y, Yano M, Takachi K, et al. (2006) Plasma D-dimer levels show correlation with number of lymph node metastases in patients with esophageal cancer. J Am Coll Surg 202(1):139–145PubMedCrossRef

21.

Javle MM, Nwogu CE, Donohue KA, et al. (2006) Management of locoregional stage esophageal cancer: a single center experience. Dis Esophagus 19:78–83PubMedCrossRef

22.

Khushalani NI, Leichman CG, Proulx G, et al. (2002) Oxaliplatin in combination with protracted-infusion fluorouracil and radiation: report of a clinical trial for patients with esophageal cancer. J Clin Oncol 20:2844–2850PubMedCrossRef

23.

Tew WP, Minsly B, Bains M et al. (2005) Phase II trial of preoperative combined modality therapy for esophageal carcinoma: induction cisplatin-irinotecan followed by concurrent cisplatin-irinotecan and radiotherapy. 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, FL. Proc Am Soc Clin Oncol 23 (16S) Part I of II: abstract 4015

24.

Kadowaki T, Shiozaki H, Inoue M, et al. (1994) E-cadherin and alpha-catenin expression in human esophageal cancer. Cancer Res 54(1):291–296PubMed

25.

Tamura S, Shiozaki H, Miyata M, et al. (1996) Decreased E-cadherin expression is associated with haematogenous recurrence and poor prognosis in patients with squamous cell carcinoma of the oesophagus. Br J Surg 83(11):1608–1614PubMedCrossRef

26.

Lin YC, Wu MY, Li DR, et al. (2004) Prognostic and clinicopathological features of E-cadherin, alpha-catenin, beta-catenin, gamma-catenin and cyclin D1 expression in human esophageal squamous cell carcinoma. World J Gastroenterol 10(22):3235–3239PubMed

27.

Zhao XJ, Li H, Chen H, et al. (2003) Expression of e-cadherin and beta-catenin in human esophageal squamous cell carcinoma: relationships with prognosis. World J Gastroenterol 9(2):225–232PubMed

28.

Zhou XB, Lu N, Zhang W, et al. (2002) Expression and significance of beta-catenin in esophageal carcinoma. Ai Zheng 21:877–880PubMed

29.

Takayama N, Arima S, Haraoka S, et al. (2003) Relationship between the expression of adhesion molecules in primary esophageal squamous cell carcinoma and metastatic lymph nodes. Anticancer Res 23:4435–4442PubMed

30.

Zhang G, Zhou X, Xue L, et al. (2005) Accumulation of cytoplasmic beta-catenin correlates with reduced expression of E-cadherin, but not with phosphorylated Akt in esophageal squamous cell carcinoma: immunohistochemical study. Pathol Int 55:310–317PubMedCrossRef

31.

Takeno S, Noguchi T, Fumoto S, et al. (2004) E-cadherin expression in patients with esophageal squamous cell carcinoma: promoter hypermethylation, snail overexpression, and clinicopathologic implication. Am J Clin Pathol 122:78–84PubMedCrossRef

32.

Uchikado Y, Natsugoe S, Okumura H, et al. (2005) Slug expression in the E-cadherin preserved tumors is related to prognosis in patients with esophageal squamous cell carcinoma. Clin Cancer Res 11(3):1174–1180PubMed

33.

Lioni M, Brafford P, Claudia A, et al. (2007) Dysregulation of claudin-7 leads to loss of E-cadherin expression and the increased invasion of esophageal squamous cell carcinoma cells. Am J Pathol 170(2):709–721PubMedCrossRef

34.

Kim JS, Crooks H, Foxworth A, et al. (2002) Proof-of-principle: oncogenic beta-catenin is a valid molecular target for the development of pharmacological inhibitors. Mol Cancer Ther 1(14):1355–1359PubMed

35.

Cong F, Zhang J, Pao W, et al. (2003) A protein knockdown strategy to study the function of beta-catenin in tumorigenesis. BMC Mol Biol 4:10PubMedCrossRef

36.

Emami K, Mguyen C, Ma H, et al. (2004) A small molecule inhibitor of beta-catenin/cyclic AMP response element-binding protein transcription. Proc Natl Acad Sci USA 101(34):12682–12687PubMedCrossRef

37.

Dillard AC, Lane MA (2007) Retinol decreases beta-catenin protein levels in retinoic acid resistant colon cancer cell lines. Mol Carcinog 46:315–329PubMedCrossRef

38.

Korst RJ, Kansler A, Port J, et al. (2006) Downstaging of T or N predicts long-term survival after preoperative chemotherapy and radical resection for esophageal carcinoma. Ann Thorac Surg 82:480–485PubMedCrossRef

39.

Brucher B, Becker K, Lordick F, et al. (2006) The clinical impact of histopathologic response assessment by residual tumor cell quantification in esophageal squamous cell carcinomas. Cancer 106:2119–2127PubMedCrossRef

40.

Swisher S, Hofstetter W, Wu T, et al. (2005) Proposed Revision of the Esophageal Cancer Staging System to Accommodate Pathologic Response (pP) Following Preoperative Chemoradiation (CRT). Ann Surg 241(5):810–820PubMedCrossRef

Title: Lymph Node Metastasis Density and Growth Pattern as Independent Prognostic Factors in Advanced Esophageal Squamous Cell Carcinoma
Authors: Akira Ooki
Keishi Yamashita
Nobuyuki Kobayashi
Natsuya Katada
Shinichi Sakuramoto
Shiroh Kikuchi
Masahiko Watanabe
Publication date: 01-11-2007
Publisher: Springer-Verlag
Published in: World Journal of Surgery / Issue 11/2007
Print ISSN: 0364-2313
Electronic ISSN: 1432-2323
DOI: https://doi.org/10.1007/s00268-007-9198-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Lymph Node Metastasis Density and Growth Pattern as Independent Prognostic Factors in Advanced Esophageal Squamous Cell Carcinoma

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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