Helen L. Figge

Decreased levels of CD44 protein and mRNA in prostate carcinoma: Correlation with tumor grade and ploidy

CD44, a transmembrane protein, is associated with cell‐cell and cell‐matrix interaction and with tumor growth and metastasis. Expression of both standard form and variant isoforms of CD44 protein has been associated with aggressive behavior and metastasis in various tumors, but has not been characterized in prostate adenocarcinoma (PAC).

Prediction of pathologic stage and postprostatectomy disease recurrence by dna ploidy analysis of initial needle biopsy specimens of prostate cancer

Background. DNA ploidy determination of carcinomas in radical prostatectomy specimens has shown significant correlation with patient outcome, but the predictive value of ploidy status of cancers obtained by transrectal ultrasound‐guided needle biopsies has not been studied extensively.

Observations on tumor and metastatic suppressor gene status in endometrial carcinoma with particular emphasis on p53

Background. Genetic changes in the development of endometrial carcinoma have not been characterized, and little is known of tumor or metastatic suppressor gene status in these malignancies. The current study on endometrioid carcinoma was undertaken to examine the status of two tumor suppressor genes that frequently have been found to be altered in human malignancies (the p53 gene and the retinoblastoma [Rb] gene) and to examine the status of the candidate metastatic suppressor gene, nm23‐H1.

Effects of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin, 12‐O‐tetradecanoylphorbol‐13‐acetate and 17β‐estradiol on estrogen receptor regulation in MCF‐7 human breast cancer cells

2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin (TCDD) exhibits remarkably potent antiestrogenic activity. To further elucidate the role of estrogen receptor (ER) regulation in this response, we examined the effects of exposure to TCDD in MCF‐7 human breast cancer cells on ER mRNA levels by using an RNase protection assay, on ER accumulation by using an ER immunocytochemical essay (ER‐ICA), and on ER function by competitive binding assays under conditions of saturating 17β‐estradiol (E2). Comparative studies were conducted with E2 and 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), as both compounds are known to suppress ER expression. Our results indicate that 1 nM E2 and 100 nM TPA both suppress ER mRNA levels as early as 4 h after exposure and to 33.6% and 16.5% of control levels, respectively, after 72 h. In contrast, no significant effect on ER mRNA levels was attributed to exposure to 10 nM TCDD. A greater than 50% reduction in positive staining was observed by ER‐ICA after 72 h exposure to 1 nM E2 and to 100 nM TPA, while only an 11% reduction in positive staining was observed with 10 nM TCDD. Specific binding of [3H]E2 under saturating conditions (10 nM E2) in whole cells was reduced by 50% in cultures exposed to 100 nM TPA, although no effect on binding was observed with exposure to 10 nM TCDD. In contrast, specific binding using subsaturating 1 nM [3H]E2 was depressed by 49% in MCF‐7 cells exposed to 10 nM TCDD for 72 h. This depression was inhibited by a 1‐h treatment with 5 μM α‐naphthoflavone, which inhibits TCDD‐induced, P450‐mediated, E2 metabolism, and subsequent E2 depletion. In conclusion, while TPA and E2 effectively down‐regulate ER expression, TCDD, under antiestrogenic conditions, has little if any effect on total ER levels in MCF‐7 cells, and thus ER modulation is probably not necessary for the suppression of estrogenic activity in MCF‐7 cells by TCDD.

Multivariate survival analysis of clinicopathologic features in surgical stage I endometrioid carcinoma including analysis of HER-2/neu expression

OBJECTIVE We previously described vascular invasion-associated changes, defined as the presence of vascular invasion or perivascular lymphocytic infiltrates, as key prognostic indicators in stage I endometrioid carcinoma. The current study was undertaken to examine the prognostic value of HER-2/neu expression in relation to other factors, including vascular invasion-associated changes, in surgical stage I endometrioid carcinoma. STUDY DESIGN Seventy-one patients with surgical stage I endometrioid carcinoma treated by hysterectomy and followed up were randomly chosen for retrospective analysis of prognostic indicators including standard clincopathologic features, deoxyribonucleic acid ploidy, and HER-2/neu expression. The latter was examined by an objective computerized quantitative immunohistochemical system. RESULTS By univariate analysis many factors were found to correlate with outcome, including age, tumor grade, depth of invasion, ploidy, HER-2/neu expression, and vascular invasion-associated changes. By multivariate analysis only vascular invasion-associated changes, aneuploidy, and HER-2/neu overexpression were found to independently correlate with survival. Stratification of patients on the basis of these three features revealed survival rates of 100%, 92%, and 60% when none, one, and two or three features were present, respectively. CONCLUSION This study suggests that HER-2/neu expression correlated with outcome independent of other factors in endometrial carcinoma and may aid in estimating prognosis. The prognostic value of HER-2/neu overexpression independent of vascular invasion suggests that this factor may operate by increasing the ability of tumor cells to grow at a distal site once vascular invasion occurs.