Prognostic value of MIB-1 in neuroendocrine tumours of the lung

Joachim Böhm, Susanne Koch, Peter Gais, Uta Jütting, Heinz W. Präuer, Heinz Höfler

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65 Scopus citations


The spectrum of neuroendocrine lung tumours ranges from highly aggressive small cell carcinomas (SCLC) to carcinoid tumours (CD) of low malignant potential. Between these two extremes, the 'well-differentiated neuroendocrine carcinomas' CWDNEC) form a transitional group with uncertain biological behaviour. This study investigated the prognostic value of the proliferation marker MIB-1 (paraffin Ki-67) in 59 neuroendocrine lung tumours (32 SCLC, 13 WDNEC, 14 CD) by immunostaining of routinely processed paraffin sections. Morphometric evaluation was done by semi-automatic image analysis. The results were compared with survival data (mean follow-up: 42 months). The proliferation rates of the tumours as determined by MIB-1 immunoreactivity (MIB-1-PR) were significantly different between the tumour types (SCLC>WDNEC>CD) and showed a strong inverse correlation with survival time. In CD, the percentage of MIB-1-labelled nuclei never exceeded 1.1 per cent; higher values would therefore favour the diagnosis of WDNEC over that of CD. Among WDNEC, MIB-1 was able to differentiate a subgroup with excellent prognosis (MIB-1-PR: 0.3-3.4 per cent) from another subgroup with a death rate of 50 per cent (MIB-1-PR: 7.3-20.3 per cent). Within each tumour type, all patients without distant metastases at diagnosis survived when MIB-1-PR was ≤9.4 per cent, suggesting a potential threshold for prognosis Although the status of metastases was the dominant prognostic factor in these neoplasms, MIB-1 was able to provide additional prognostic information allowing the definition of prognostically different subgroups of patients. In conclusion, MIB-1 and tile status of metastases are complementary prognostic indicators and are best used in combination to characterize the biological behaviour of neuroendocrine lung tumours.

Original languageEnglish
Pages (from-to)402-409
Number of pages8
JournalJournal of Pathology
Issue number4
StatePublished - 1996


  • Carcinoid
  • Ki-67
  • MIB-1
  • Neuroendocrine lung tumours
  • Prognosis
  • Small cell carcinoma


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