Skip to main content
Erschienen in: Esophagus 4/2012

01.12.2012 | Original Article

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

verfasst von: 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

Erschienen in: Esophagus | Ausgabe 4/2012

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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
Metadaten
Titel
Ki-67 labeling index as an independent prognostic factor in human esophageal squamous cell carcinoma
verfasst von
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
Publikationsdatum
01.12.2012
Verlag
Springer Japan
Erschienen in
Esophagus / Ausgabe 4/2012
Print ISSN: 1612-9059
Elektronische ISSN: 1612-9067
DOI
https://doi.org/10.1007/s10388-012-0336-6

Weitere Artikel der Ausgabe 4/2012

Esophagus 4/2012 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Echinokokkose medikamentös behandeln oder operieren?

06.05.2024 DCK 2024 Kongressbericht

Die Therapie von Echinokokkosen sollte immer in spezialisierten Zentren erfolgen. Eine symptomlose Echinokokkose kann – egal ob von Hunde- oder Fuchsbandwurm ausgelöst – konservativ erfolgen. Wenn eine Op. nötig ist, kann es sinnvoll sein, vorher Zysten zu leeren und zu desinfizieren. 

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Proximale Humerusfraktur: Auch 100-Jährige operieren?

01.05.2024 DCK 2024 Kongressbericht

Mit dem demographischen Wandel versorgt auch die Chirurgie immer mehr betagte Menschen. Von Entwicklungen wie Fast-Track können auch ältere Menschen profitieren und bei proximaler Humerusfraktur können selbst manche 100-Jährige noch sicher operiert werden.

Die „Zehn Gebote“ des Endokarditis-Managements

30.04.2024 Endokarditis Leitlinie kompakt

Worauf kommt es beim Management von Personen mit infektiöser Endokarditis an? Eine Kardiologin und ein Kardiologe fassen die zehn wichtigsten Punkte der neuen ESC-Leitlinie zusammen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.