Expression of bcl-2 in invasive and in situ carcinoma of the uterine cervix.

OBJECTIVE: The oncoprotein bcl-2 inhibits apoptosis. The purpose of this study was to assess the expression of bcl-2 in human cervical carcinoma and to correlate this with clinicopathologic parameters. STUDY DESIGN: Immunohistochemical staining for bcl-2 protein (MoAB clone 124) was performed on operative tissue specimens from 22 patients with carcinoma in situ of the cervix and from 137 patients with invasive cervical carcinoma (International Federation of Gynecology and Obstetrics stages I to IV). The immunoreactivity of bcl-2 was scored as positive (> or = 5% staining cells) or negative (< 5% staining cells). RESULTS: Eighty-two percent of in situ carcinomas and 61% of invasive cervical carcinomas were bcl-2 positive. Expression of bcl-2 was correlated to tumor stage (p < 0.001) and to presence of vascular (p < 0.005) or lymphatic tumor (p < 0.023) permeation. In univariate analysis there was a strong relationship between bcl-2 expression and overall survival (p < 0.001). In multivariate analysis bcl-2 expression (p < 0.001), International Federation of Gynecology and Obstetrics stage (p = 0.011), and presence of lymphatic permeation (p = 0.014) proved to be independent prognostic factors. CONCLUSIONS: Expression of bcl-2 is lost during tumor progression and is a strong prognostic parameter, suggesting that the regulation of apoptosis plays an important role in the behavior of cervical carcinomas. Better understanding of the mechanisms involved may lead to improved medical treatment strategies.

Higher levels of interleukin-6 in cystic fluids from patients with malignant versus benign ovarian tumors correlate with decreased hemoglobin levels and increased platelet counts.

BACKGROUND: Recently, high pretreatment platelet counts and low pretreatment hemoglobin levels were found to be negative prognostic factors in patients with ovarian cancer. Interleukin-6 (IL-6) is a multifunctional cytokine with a diversity of functions leading to the induction of C-reactive protein (CRP), increased platelet counts, and low hemoglobin levels. Different epithelial ovarian cancer cell lines are found to produce varying amounts of IL-6. In this study, a possible relationship between IL-6 levels in cystic fluids of benign and malignant ovarian tumors and pretreatment serum CRP, platelet counts, and hemoglobin levels was evaluated. METHODS: A bioassay and enzyme-linked immunosorbent assay (ELISA) were performed to determine the IL-6 levels in cystic fluids and serum from 42 patients with benign and malignant ovarian tumors. RESULTS: The median IL-6 level was higher in cystic fluids of malignant tumors (n = 21) when compared with cystic fluids of benign tumors (n = 21) (P < 0.01 for bioassay and ELISA). Serum IL-6 levels in patients with malignant tumors were not significantly higher compared with IL-6 levels in patients with benign tumors, whereas CRP levels were higher in patients with malignant tumors (P < 0.01). Cystic fluid IL-6 levels were related to serum CRP levels (r = 0.60, P < 0.01 [bioassay]; r = 0.41, P < 0.01 [ELISA]), and were related inversely to hemoglobin levels (r = -0.57, P < 0.01 [bioassay]; r = 0.54, P < 0.01 [ELISA]). CONCLUSIONS: IL-6 levels are higher in cystic fluids of malignant ovarian tumors compared with benign tumors. The relationship of cystic fluid IL-6 levels with CRP, platelet counts, and hemoglobin levels suggests a possible causative role of tumor-derived IL-6 in the appearance of general side effects of ovarian cancer, which recently have been recognized as prognostic factors.