Tomas M. Heinrich

Acid ceramidase is associated with an improved prognosis in both DCIS and invasive breast cancer

Acid ceramidase (ASAH1) a key enzyme of sphingolipid metabolism converting pro‐apoptotic ceramide to sphingosine has been shown to be overexpressed in various cancers. We previously demonstrated higher expression of ASAH1 in ER positive compared to ER negative breast cancer. In the current study we performed subtype specific analyses of ASAH1 gene expression in invasive and non invasive breast cancer. We show that expression of ASAH1 is mainly associated with luminal A – like cancers which are known to have the best prognosis of all breast cancer subtypes. Moreover tumors with high ASAH1 expression among the other subtypes are also characterized by an improved prognosis. The good prognosis of tumors with high ASAH1 is independent of the type of adjuvant treatment in breast cancer and is also detected in non small cell lung cancer patients. Moreover, even in pre‐invasive DCIS of the breast ASAH1 is associated with a luminal phenotype and a reduced frequency of recurrences. Thus, high ASAH1 expression is generally associated with an improved prognosis in invasive breast cancer independent of adjuvant treatment and could also be valuable as prognostic factor for pre‐invasive DCIS.

OPG and PgR show similar cohort specific effects as prognostic factors in ER positive breast cancer.

The RANK/RANKL/OPG pathway is well known for bone destruction in skeletal metastases but has also been implicated in osteoclast‐independent roles in tumorigenesis and de novo metastasis. Experimental data suggest contribution of progesterone to tumorigenesis may be mediated by RANKL. Importantly, modulation of this pathway became possible through the availability of denosumab, an artificial counterpart of OPG, but significant gaps remain in the translation of preclinical findings on the pathway. We analyzed gene expression of RANK, RANKL and OPG from 40 Affymetrix datasets encompassing 4467 primary breast cancers and focused on ER positive disease.

Acid ceramidase (AC)--a key enzyme of sphingolipid metabolism--correlates with better prognosis in epithelial ovarian cancer.

Acid ceramidase (AC), a key enzyme of sphingolipid metabolism, seems to play an important role in cancer progression. The objective of this study was to explore the expression of AC in ovarian cancer and its impact on prognosis. Expression analysis of AC in n=112 ovarian cancer patients was performed by immunohistochemical analysis of primary paraffin-embedded tumor samples. The results were scored on the basis of the staining intensity and percentage of positive tumor cells, resulting in an immunoreactive score from 0 to 12. These results were correlated to clinical and pathologic characteristics and survival. AC expression correlated significantly only with FIGO stage (0.047). In serous carcinoma, low level of AC was independently associated with reduced progression-free survival and overall survival of 12.0 mo [95% confidence interval (CI), 5.78–18.23] versus 18.1 mo (95% CI, 11.61–24.59; P=0.008) and 35.7 mo (95% CI, 22.24–47.16) versus 58.7 mo (95% CI, 36.48–80.91; P=0.032), respectively. In multivariate analysis, AC presents as an independent prognostic factor for progression-free survival (hazard ratio 1.88; 95% CI, 1.13–3.11; P=0.015). AC is a prognostic factor in epithelial ovarian cancer. Low AC expression can be associated with tumor progression in carcinoma of the ovaries. These results are in contrast to the concept of AC as a promoter for cancer progression. Nevertheless, they are supported by the lately discovered tumor-suppressing function of sphingosine, the enzymatic product of AC.

Clinical Hypnosis Before External Cephalic Version

Three to four percent of full-term singleton pregnancies present themselves as breech deliveries. External cephalic version (ECV) is a procedure to try to turn a breech fetus to cephalic by externally maneuvering the fetus through the maternal abdomen. This trial examines a clinical hypnosis intervention against standard medical care of women before ECV. A total of 78 women, who received a hypnosis intervention prior to ECV, had a 41.6% (n = 32) successful ECV, whereas the control group of 122, who had similar baseline characteristics, had a 27.3% (n = 33) successful ECV procedure (p < 0.05). This trial found that a relaxation technique with the help of clinical hypnosis was successful at increasing the likelihood of a successful ECV procedure.