ABSTRACT
OBJECTIVES: Theprognostic value of p53 expression in epithelial ovarian cancer remains unresolved. We hypothesized that prognosis may relate more to expression of p21(waf1/cip1), the major downstream effector of p53, which can also be induced through p53-independent mechanisms. We therefore studied the relationship of p53 and p21(waf1/cip1) expression in epithelial ovarian cancers to clinicopathological variables and prognosis. METHODS: Fixed, embedded tumors from 85 patients with untreated, primary epithelial ovarian cancer were immunostained with antibodies to p53 and p21(waf1/cip1). Expression was correlated with clinicopathological features and prognosis. Survival curves were calculated by the Kaplan-Meier method and compared using the log-rank test for p53, p21(waf1/cip1), and all combinations of expression of the two markers. RESULTS: Sixty-two percent of tumors expressed p53, and 42% expressed p21(waf1/cip1). There was no correlation between p53 and p21(waf1/cip1) expression. Advanced stage, grade, age >/=50, and p53 expression were associated with worse disease-free survival. Patients whose tumors were p53(+)/waf1(-), however, had a particularly strong association with poorer disease-free survival when compared with other combinations of p53 and p21(waf1/cip1) expression (P = 0.003). Neither p53, nor p21(waf1/cip1), nor combinations of expression were independently related to survival when histology, age, stage, and differentiation were considered. CONCLUSIONS: p53 expression in the absence of p21(waf1/cip1) expression is a better marker of poor prognosis than either p53 or p21(waf1/cip1) expression status alone in univariate analysis. Absence of independent prognostic significance may be related to the paucity of early stage cases in the current study.
Subject(s)
Cyclins/analysis , Neoplasms, Glandular and Epithelial/chemistry , Ovarian Neoplasms/chemistry , Tumor Suppressor Protein p53/analysis , Cyclin-Dependent Kinase Inhibitor p21 , Female , Humans , Immunohistochemistry , Neoplasm Recurrence, Local/chemistry , Neoplasms, Glandular and Epithelial/mortality , Ovarian Neoplasms/mortality , Ovary/chemistry , PrognosisABSTRACT
Tumor necrosis factor alpha (TNF alpha) and interleukin 6 (IL6) are cytokines with a varied spectrum of inflammatory and immunological activities, for example modulation of acute phase proteins, fever and stimulation of B-lymphocytes. Mycobacterium avium has been shown to stimulate the release of TNF alpha and IL6 from cultured human monocytes and macrophages into the cell supernatant. Cultured human monocytes were infected with Mycobacterium kansasii and M. avium. The concentrations of TNF alpha and IL6 were measured in the supernatant. Monocytes infected with M. kansasii produced significantly lower amounts of TNF alpha (34.8 +/- 20.3 pg/ml) and IL6 (12.0 +/- 8.9 pg/ml) compared to monocytes infected with M. avium (198.3 +/- 171.7 pg/ml and 63.2 +/- 37.6 pg/ml respectively). The extent of cytokine production might be relevant for the clinical manifestation of mycobacterial disease.
