Biomedical subjects

Eric Kielhorn

Publications and source records attributed to Eric Kielhorn.

3 recordsLinked to original sources

PubMed2003

Subcellular localization of activating transcription factor 2 in melanoma specimens predicts patient survival.

The transcription factor activating transcription factor 2 (ATF2) has been shown to be associated with melanocytic oncogenesis and melanoma tumor proliferation in preclinical models. The clinical significance of ATF2 expression is unknown. To determine the prognostic value of ATF2 in melanoma, we evaluated the pattern and level of ATF2 expression in a large cohort of melanoma specimens. Immunohistochemical staining was performed on a tissue microarray representing 544 patients with a mean follow-up time of 60 months. Expression was evaluated semiquantitatively and correlated with overall survival and other clinicopathological data. Strong cytoplasmic ATF2 expression was associated with primary specimens rather than metastases (P < 0.0001) and with better survival (P = 0.0003). Strong nuclear ATF2 expression was associated with metastatic specimens (P < 0.0001) and with poor survival (P = 0.0008). Patients who had both weak cytoplasmic and strong nuclear ATF2 staining had the worst outcome, both among the full cohort of patients (P < 0.0001) and among the patients with localized disease (n = 269; P < 0.0001). On multivariate analysis of the primary cutaneous specimens, weak cytoplasmic staining and strong nuclear staining was an independent predictor of poor outcome, as was Clark level. Nuclear ATF2 is likely to be transcriptionally active, whereas cytoplasmic ATF2 probably represents an inactive form. These findings support other preclinical findings in which transcriptionally active ATF2 is involved in tumor progression-proliferation in melanoma. Moreover, our findings suggest that ATF2 might be a useful prognostic marker in early-stage melanoma.

Activating Transcription Factor 2↗

PubMed2003

Tissue microarray-based analysis shows phospho-beta-catenin expression in malignant melanoma is associated with poor outcome.

Beyond depth of invasion, there are very few prognostic markers to predict outcome in melanoma. It has been shown recently that the beta-catenin oncogene is mutated or shows altered subcellular localization suggesting that activation of beta-catenin mediated signaling plays a role in oncogenesis. We hypothesize that assessment of activated beta-catenin, as detected by a phospho-specific antibody, may be useful to predict outcome in melanoma. We use immuno-histochemical analysis of beta-catenin and phospho-beta-catenin, first to verify the specificity of the phospho-beta-catenin antibody and then to assay expression in a tissue microarray-based study. The subcellular localization of beta-catenin is membranous in some cases and cytoplasmic and nuclear in others. We validate the specificity of a ser33/37/thr41 phospho-beta-catenin antibody in transfected cells and show that the expression is almost exclusively localized to the nucleus in both cultured cells and human tissue. Evaluation of both total and phospho-beta-catenin antibodies showed that cytoplasmic/nuclear staining was more common in primary lesions, whereas nuclear phospho-beta-catenin was more common in metastatic lesions. High levels of nuclear phospho-beta-catenin are associated with significantly worse overall survival (51% vs. 25% overall survival at 5 years, p = 0.046). These results suggest that phospho-specific antibodies to beta-catenin define a unique subset of cases and that monitoring of phospho-beta-catenin expression may be useful for assessing prognosis in malignant melanoma.

Cell Nucleus↗

PubMed2002

Use of magnetic enrichment for detection of carcinoma cells in fluid specimens.

BACKGROUND: Ascites fluid or a pleural effusion are common events in metastatic carcinoma, but they also can be associated with several other medical conditions. The standard for determination of malignancy in these situations is cytologic evaluation of these fluids. Although this method is frequently successful, there are times when it fails, even when the patient has a malignancy, either because of insufficient cells in the fluid or for other reasons. This study addresses this problem taking advantage of the recent advances in technology for detection of rare epithelial cells in liquid specimens. METHODS: The authors examined fluid specimens from 59 patients to determine the frequency of recovery of epithelial cells compared with that achieved by conventional cytopathology. The Dynal CELLection Epithelial Enrich (Dynal AS, Oslo, Norway) method was used. This method is based on immunomagnetic selection of cells binding to EpCAM antibodies. Carcinoma cells were confirmed by morphology and, when there was sufficient material, by E-cadherin staining. RESULTS: Grouping the cases by cytologic diagnosis, the authors found malignant cells using the cell enrichment assay in 11 of 12 malignant cases, 2 of 5 atypical cases, and 3 of 42 negative cases. Further investigations were conducted on the five cases that were cytologically negative or atypical but yielded epithelial cells after immunomagnetic enrichment. Four cases ultimately were proven malignant by other methods and one had incomplete follow-up. CONCLUSIONS: The new methods available for epithelial cell enrichment in liquids may be used successfully on cytologic fluid specimens and may lead to increased sensitivity for detection of malignancy, and consequently more accurate staging.

Ascites↗