Skip to main content
Top
Published in: Esophagus 4/2012

01-12-2012 | Original Article

Ki-67 labeling index as an independent prognostic factor in human esophageal squamous cell carcinoma

Authors: Hisami Sasagawa, Atsushi Shiozaki, Daisuke Iitaka, Daisuke Ichikawa, Shuhei Komatsu, Hitoshi Fujiwara, Kazuma Okamoto, Shingo Nakashima, Osamu Kinoshita, Yasutoshi Murayama, Yoshiaki Kuriu, Hisashi Ikoma, Masayoshi Nakanishi, Toshiya Ochiai, Yukihito Kokuba, Eigo Otsuji

Published in: Esophagus | Issue 4/2012

Login to get access

Abstract

Background

Although the Ki-67 labeling index (LI) is frequently used to determine the proliferative activity of malignant tumors, no consensus has been reached about its clinicopathological significance in esophageal squamous cell carcinoma (ESCC). In this study, we sought to determine an adequate Ki-67 LI cutoff value and investigated its prognostic significance in ESCC.

Methods

The Ki-67 LI was calculated by immunohistochemistry for 49 primary tumor samples obtained from ESCC patients who had undergone curative esophagectomy, and the correlations between the Ki-67 LI and various clinicopathological features or prognosis were analyzed.

Results

The Ki-67 LI of the tumors ranged from 5.3 to 55.9 %. The mean Ki-67 LI increased from 27.4 % in pN0 tumors to 40.3 % in pN3 tumors. The 5-year survival rate decreased as the Ki-67 LI increased. When the patients were divided into two groups using an Ki-67 LI cutoff value of 35 %, the 5-year survival rate of the patients with Ki-67 LI of <35 % was 82.9 %, which was significantly higher than that of the patients with Ki-67 LI of ≥35 % (35.7 %). The percentage of pN-positive tumors was significantly higher among the patients with Ki-67 LI of ≥35 % (85.7 %) than in patients with Ki-67 LI of <35 (48.6 %). Multivariate analysis demonstrated that pT and pN categories and the Ki-67 LI were independent prognostic factors.

Conclusions

These observations indicate that the Ki-67 LI is correlated with lymph node metastasis and can be used as an independent prognostic factor for ESCC patients by selecting an adequate cutoff value.
Literature
1.
go back to reference Daly JM, Fry WA, Little AG, Winchester DP, McKee RF, Stewart AK, et al. Esophageal cancer: results of an American College of Surgeons Patient Care Evaluation Study. J Am Coll Surg. 2000;190:562–73.PubMedCrossRef Daly JM, Fry WA, Little AG, Winchester DP, McKee RF, Stewart AK, et al. Esophageal cancer: results of an American College of Surgeons Patient Care Evaluation Study. J Am Coll Surg. 2000;190:562–73.PubMedCrossRef
2.
go back to reference Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006;24:2137–50.PubMedCrossRef Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006;24:2137–50.PubMedCrossRef
3.
go back to reference Ozawa S, Tachimori Y, Baba H, Fujishiro M, Matsubara H, Numasaki H, et al. Comprehensive registry of esophageal cancer in Japan, 2003. Esophagus. 2011;8:9–29.CrossRef Ozawa S, Tachimori Y, Baba H, Fujishiro M, Matsubara H, Numasaki H, et al. Comprehensive registry of esophageal cancer in Japan, 2003. Esophagus. 2011;8:9–29.CrossRef
4.
go back to reference Ando N, Ozawa S, Kitagawa Y, Shinozawa Y, Kitajima M. Improvement in the results of surgical treatment of advanced squamous esophageal carcinoma during 15 consecutive years. Ann Surg. 2000;232:225–32.PubMedCrossRef Ando N, Ozawa S, Kitagawa Y, Shinozawa Y, Kitajima M. Improvement in the results of surgical treatment of advanced squamous esophageal carcinoma during 15 consecutive years. Ann Surg. 2000;232:225–32.PubMedCrossRef
5.
go back to reference Nakagawa S, Kanda T, Kosugi S, Ohashi M, Suzuki T, Hatakeyama K. Recurrence pattern of squamous cell carcinoma of the thoracic esophagus after extended radical esophagectomy with three-field lymphadenectomy. J Am Coll Surg. 2004;198:205–11.PubMedCrossRef Nakagawa S, Kanda T, Kosugi S, Ohashi M, Suzuki T, Hatakeyama K. Recurrence pattern of squamous cell carcinoma of the thoracic esophagus after extended radical esophagectomy with three-field lymphadenectomy. J Am Coll Surg. 2004;198:205–11.PubMedCrossRef
6.
go back to reference Shimada H, Kitabayashi H, Nabeya Y, Okazumi S, Matsubara H, Funami Y, et al. Treatment response and prognosis of patients after recurrence of esophageal cancer. Surgery. 2003;133:24–31.PubMedCrossRef Shimada H, Kitabayashi H, Nabeya Y, Okazumi S, Matsubara H, Funami Y, et al. Treatment response and prognosis of patients after recurrence of esophageal cancer. Surgery. 2003;133:24–31.PubMedCrossRef
7.
go back to reference Kunisaki C, Makino H, Takagawa R, Yamamoto N, Nagano Y, Fujii S, et al. Surgical outcomes in esophageal cancer patients with tumor recurrence after curative esophagectomy. J Gastrointest Surg. 2008;12:802–10.PubMedCrossRef Kunisaki C, Makino H, Takagawa R, Yamamoto N, Nagano Y, Fujii S, et al. Surgical outcomes in esophageal cancer patients with tumor recurrence after curative esophagectomy. J Gastrointest Surg. 2008;12:802–10.PubMedCrossRef
8.
go back to reference Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol. 1984;133:1710–5.PubMed Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol. 1984;133:1710–5.PubMed
9.
go back to reference Youssef EM, Matsuda T, Takada N, Osugi H, Higashino M, Kinoshita H, et al. Prognostic significance of the MIB-1 proliferation index for patients with squamous cell carcinoma of the esophagus. Cancer. 1995;76:358–66.PubMedCrossRef Youssef EM, Matsuda T, Takada N, Osugi H, Higashino M, Kinoshita H, et al. Prognostic significance of the MIB-1 proliferation index for patients with squamous cell carcinoma of the esophagus. Cancer. 1995;76:358–66.PubMedCrossRef
10.
go back to reference Ikeda G, Isaji S, Chandra B, Watanabe M, Kawarada Y. Prognostic significance of biologic factors in squamous cell carcinoma of the esophagus. Cancer. 1999;86:1396–405.PubMedCrossRef Ikeda G, Isaji S, Chandra B, Watanabe M, Kawarada Y. Prognostic significance of biologic factors in squamous cell carcinoma of the esophagus. Cancer. 1999;86:1396–405.PubMedCrossRef
11.
go back to reference Sarbia M, Bittinger F, Porschen R, Dutkowski P, Torzewski M, Willers R, et al. The prognostic significance of tumour cell proliferation in squamous cell carcinomas of the oesophagus. Br J Cancer. 1996;74:1012–6.PubMedCrossRef Sarbia M, Bittinger F, Porschen R, Dutkowski P, Torzewski M, Willers R, et al. The prognostic significance of tumour cell proliferation in squamous cell carcinomas of the oesophagus. Br J Cancer. 1996;74:1012–6.PubMedCrossRef
12.
go back to reference Chino O, Osamura Y, Kise Y, Nishi T, Shimada H, Tanaka M, et al. Acceleration of the proliferative activity of esophageal carcinoma with invasion beyond the muscularis mucosae; immunohistochemical analysis using MIB-1 for the Ki-67 antigen. Tokai J Exp Clin Med. 2007;32:115–20.PubMed Chino O, Osamura Y, Kise Y, Nishi T, Shimada H, Tanaka M, et al. Acceleration of the proliferative activity of esophageal carcinoma with invasion beyond the muscularis mucosae; immunohistochemical analysis using MIB-1 for the Ki-67 antigen. Tokai J Exp Clin Med. 2007;32:115–20.PubMed
13.
go back to reference Porschen R, Kriegel A, Langen C, Classen S, Hilse M, Lohe B, et al. Assessment of proliferative activity in carcinomas of the human alimentary tract by Ki-67 immunostaining. Int J Cancer. 1991;47:686–91.PubMedCrossRef Porschen R, Kriegel A, Langen C, Classen S, Hilse M, Lohe B, et al. Assessment of proliferative activity in carcinomas of the human alimentary tract by Ki-67 immunostaining. Int J Cancer. 1991;47:686–91.PubMedCrossRef
14.
go back to reference Imdahl A, Jenkner J, Ihling C, Rückauer K, Farthmann EH. Is MIB-1 proliferation index a predictor for response to neoadjuvant therapy in patients with esophageal cancer? Am J Surg. 2000;179:514–20.PubMedCrossRef Imdahl A, Jenkner J, Ihling C, Rückauer K, Farthmann EH. Is MIB-1 proliferation index a predictor for response to neoadjuvant therapy in patients with esophageal cancer? Am J Surg. 2000;179:514–20.PubMedCrossRef
15.
go back to reference Sobin L, Gospodarowicz M, Wittekind C, editors. TNM Classification of malignant tumors. 7th ed. Hoboken: Wiley.; 2009. Sobin L, Gospodarowicz M, Wittekind C, editors. TNM Classification of malignant tumors. 7th ed. Hoboken: Wiley.; 2009.
16.
go back to reference Gerdes J, Schwab U, Lemke H, Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer. 1983;31:13–20.PubMedCrossRef Gerdes J, Schwab U, Lemke H, Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer. 1983;31:13–20.PubMedCrossRef
17.
go back to reference Al-Sheneber IF, Shibata HR, Sampalis J, Jothy S. Prognostic significance of proliferating cell nuclear antigen expression in colorectal cancer. Cancer. 1993;71:1954–9.PubMedCrossRef Al-Sheneber IF, Shibata HR, Sampalis J, Jothy S. Prognostic significance of proliferating cell nuclear antigen expression in colorectal cancer. Cancer. 1993;71:1954–9.PubMedCrossRef
18.
go back to reference Mayer A, Takimoto M, Fritz E, Schellander G, Kofler K, Ludwig H. The prognostic significance of proliferating cell nuclear antigen, epidermal growth factor receptor, and mdr gene expression in colorectal cancer. Cancer. 1993;71:2454–60.PubMedCrossRef Mayer A, Takimoto M, Fritz E, Schellander G, Kofler K, Ludwig H. The prognostic significance of proliferating cell nuclear antigen, epidermal growth factor receptor, and mdr gene expression in colorectal cancer. Cancer. 1993;71:2454–60.PubMedCrossRef
19.
go back to reference Kubota Y, Petras RE, Easley KA, Bauer TW, Tubbs RR, Fazio VW. Ki-67-determined growth fraction versus standard staging and grading parameters in colorectal carcinoma. A multivariate analysis. Cancer. 1992;70:2602–9.PubMedCrossRef Kubota Y, Petras RE, Easley KA, Bauer TW, Tubbs RR, Fazio VW. Ki-67-determined growth fraction versus standard staging and grading parameters in colorectal carcinoma. A multivariate analysis. Cancer. 1992;70:2602–9.PubMedCrossRef
20.
go back to reference Tachibana M, Kinugasa S, Yoshimura H, Shibakita M, Tonomoto Y, Dhar DK, et al. Clinical outcomes of extended esophagectomy with three-field lymph node dissection for esophageal squamous cell carcinoma. Am J Surg. 2005;189:98–109.PubMedCrossRef Tachibana M, Kinugasa S, Yoshimura H, Shibakita M, Tonomoto Y, Dhar DK, et al. Clinical outcomes of extended esophagectomy with three-field lymph node dissection for esophageal squamous cell carcinoma. Am J Surg. 2005;189:98–109.PubMedCrossRef
Metadata
Title
Ki-67 labeling index as an independent prognostic factor in human esophageal squamous cell carcinoma
Authors
Hisami Sasagawa
Atsushi Shiozaki
Daisuke Iitaka
Daisuke Ichikawa
Shuhei Komatsu
Hitoshi Fujiwara
Kazuma Okamoto
Shingo Nakashima
Osamu Kinoshita
Yasutoshi Murayama
Yoshiaki Kuriu
Hisashi Ikoma
Masayoshi Nakanishi
Toshiya Ochiai
Yukihito Kokuba
Eigo Otsuji
Publication date
01-12-2012
Publisher
Springer Japan
Published in
Esophagus / Issue 4/2012
Print ISSN: 1612-9059
Electronic ISSN: 1612-9067
DOI
https://doi.org/10.1007/s10388-012-0336-6

Other articles of this Issue 4/2012

Esophagus 4/2012 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.