Histotype-specific analysis of acid ceramidase expression in ovarian cancer.

Acid ceramidase (ASAH1) is a key player in sphingolipid metabolism and signaling. It has prognostic value for several cancers, but histotype-specific analyses of ovarian cancer are not yet available. We used three retrospective TMA cohorts encompassing a total of 1106 ovarian cancers with follow-up data for immunohistochemical analysis of acid ceramidase (ASAH1) expression. Patients with sub-optimal debulking and persistent residual tumor after surgery introduced bias in the prognostic analysis and were excluded from further studies. Overall, we detected an association of ASAH1 expression with better prognosis in ovarian cancer patients. ASAH1 expression differed between histological ovarian cancer histotypes with most frequent expression in endometrioid and clear cell ovarian cancer, which are both associated with good prognosis. Stratified subgroup analyses within these histotypes did not reveal significant survival differences, but the power of the analysis may be limited by smaller sample sizes. In contrast to breast cancer, we found only a modest concordance between estrogen receptor status and ASAH1 expression within the endometrioid ovarian cancer histotype. In an exploratory analysis of estrogen receptor negative endometrioid ovarian cancer, ASAH1 expression was associated with significantly better overall survival (P = 0.007). Acid ceramidase is most frequently expressed in endometrioid and clear cell histotypes and could add independent prognostic value to estrogen receptor in endometrioid ovarian cancer. Modulating sphingolipid metabolism may lead to novel therapeutic intervention strategies for this disease.

Immunolocalization of lactoferrin in healthy and inflamed gingival tissues.

BACKGROUND: It has been reported that lactoferrin prevents biofilm formation and exerts antimicrobial activity. The aim of the present study was to evaluate the cellular source of lactoferrin in healthy and inflamed gingiva. METHODS: Lactoferrin synthesis was examined in relation to disease manifestation in biopsies of the marginal gingiva by immunohistochemistry. The expression of lactoferrin in cell cultures was studied by immunocytochemistry and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Healthy gingiva demonstrated no immunoreactivity to lactoferrin in epithelial and connective tissue cells. In inflamed specimens, lactoferrin staining was related to inflammatory cells. These results were confirmed by cell cultures of keratinocytes that did not show any immunoreactivity against lactoferrin. No mRNA message for lactoferrin was detected by RT-PCR in keratinocytes. CONCLUSIONS: These data provide evidence that lactoferrin is not synthesized in healthy gingival tissues. Therefore, elevated lactoferrin levels in the crevicular fluid of inflamed tissues originate from invading cells of the inflammatory reaction.