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Expression of IGF-I, IGF-II, and IGF-IR in gallbladder carcinoma. A systematic analysis including primary and corresponding metastatic tumours

¹ Department of Surgery, Medical University Graz, Auenbruggerplatz 29, A-8036 Graz, Austria
² Division of Biomedical Engineering and Computing, Department of Surgery, Medical University Graz
³ Institute of Pathology, Klinikum Kassel, Mönchebergstr. 41-43, D-34125 Kassel, Germany
⁴ Institute of Pathology, Medical University Graz

Correspondence to:
Dr C Langner
Institute of Pathology, Medical University Graz, Auenbruggerplatz 25, A-8036 Graz, Austria; cord.langner{at}meduni-graz.at Aims: The insulin-like growth factor (IGF) system has been implicated in tumour development and progression. This study was designed to analyse the expression of the IGF-I receptor (IGF-IR) and its ligands (IGF-I, IGF-II) in gallbladder cancer.

Methods: IGF-I, IGF-II, and IGF-IR immunoreactivity was investigated in 57 gallbladder carcinomas and corresponding lymph node (n = 11) and hepatic (n = 7) metastases using a tissue microarray technique and correlated with tumour stage, grade, and patient outcome.

Results: Cancer tissue allowing a reliable evaluation of IGF-I, IGF-II, and IGF-IR was present in 55 of 57 primary tumours and 17 of 18 metastases. IGF-I and IGF-II immunoreactivity was seen in 25 and 14 of the 55 primary tumours, in addition to six and three of the 17 metastases, respectively. No associations with tumour stage, grade, or prognosis were detected. IGF-IR was expressed in 52 of 55 primary tumours and all 17 metastases. IGF-IR staining intensity decreased with tumour cell dedifferentiation. Moreover, IGF-IR expression in less than 50% of cancer cells was an independent marker of poor prognosis in multivariate analysis (risk ratio, 4.0; 95% confidence interval, 1.4 to 11.2; p = 0.01).

Conclusions: The expression of IGF-IR and its ligands provides evidence for the existence of an auto/paracrine loop of tumour cell stimulation in gallbladder cancer and makes this type of cancer a candidate for therapeutic strategies aimed at interfering with the IGF pathway. The recognition of IGF-IR as a new independent prognostic biomarker may help to identify patients who might benefit from adjuvant treatment.

Abbreviations: CI, confidence interval; IGF-I/II, insulin-like growth factor type I/II; IGF-IR, insulin-like growth factor type I receptor; RR, relative risk; TMA, tissue microarray

Keywords: insulin-like growth factors; insulin-like growth factor receptor; immunohistochemistry; gallbladder cancer; prognosis

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