ErbB-2/HER-2 protein expression, serum tumour necrosis factor-a (TFM-a) and soluble tumour necrosis factor receptor-2 (TNFR-2) concentrations in human carcinoma of the uterine cervix

The expression of erbB-2 protein (by immunohistochemistry), serum TNF-alpha, soluble TNF-receptor 2 (sTNFR-2, ELISA) concentrations and mitogenic (LPS, ConA, PHA) induced TNF-alpha production of the peripheral blood mononuclear cells (PBMNC) were studied in 91 (UICC Stage 1: 39, Stage 2: 33, Stage 3: 14, Stage 4: 5) patients with carcinoma of the uterine cervix. During a follow-up period of seven years 30 patients died (Stage 4: 5, Stage 3: 12, Stage 2: 11, Stage 1: 2). ErbB-2 protein expression was significantly more frequent in patients with UICC Stages 3-4 (14/19), and in those with fatal outcomes (14/30, p < 0.0001, chi-square test). Serum TNF-alpha (2.70 +/- 0.69 pg/ml) and sTNFR-2 (3.85 +/- 1.05 ng/ml) concentrations were significantly lower in cancer patients (p < 0.0001, Mann-Whitney test) as compared to 64 age-matched control women (TNF-alpha: 4.32 +/- 0.36, TNFR-2: 4.85 +/- 0.82). The mitogenic induced TNF-alpha production of PBMNC was also significantly less with all the three mitogens applied (LPS: 35.24 +/- 8.84, ConA: 26.28 +/- 7.81, PHA: 20.48 +/- 7.04 pg/l million of cells/24 hours, p < 0.0001) as compared to the controls (LPS: 65.33 +/- 8.82, ConA: 51.00 +/- 8.87, PHA: 41.80 +/- 9.01). Serum TNF-alpha, sTNFR-2 concentrations and the mitogenic induced TNF-alpha production of PBMNC was significantly decreased in patients with erbB-2 positivity as compared to those with negativity. In conclusion the expression of the oncoprotein and the lower levels of the members of the TNF system seem to be poor prognostic parameters in patients with carcinoma of the uterine cervix.

TNF-a; TNFR-2; ErbB-2; Cervical cancer

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