Prognostic significance of nuclear DNA content and S-phase fraction by flow cytometry in primary papillary superficial bladder cancer.

This study is aimed at determining the usefulness of nuclear DNA content and S-phase fraction (SPF) to predict tumor recurrence in papillary superficial bladder cancer. Tumor DNA content and SPF were measured by flow cytometry on formalin-fixed, paraffin-embedded tissue from 199 newly diagnosed pTa/pT1 transitional cell carcinomas of patients enrolled into a multicenter prospective study from 1990 to 1992. The follow-up extended up to March 1994, and, at last follow-up, 122 (61.3%) patients have experienced at least one recurrence. After exclusion of 34 cases, whose coefficient of variation exceeded 8%, 131 (79.4%) tumors were diploid, and 34 (20.6%) were aneuploid. There was no association between tumor DNA content and time to first recurrence. Diploid tumors with low SPF (< 11%) tended to have a longer recurrence-free survival (RFS) than those with high SPF, but this difference did not reach statistical significance (P = .2833). SPF in aneuploid tumors did not add any new information. Aneuploidy was associated with higher stage (P < .001), poorer grade (P < .002), multifocality (P = .028), Her-2/neu (P = .021), and p53 (P = .033) expression. High SPF correlated with higher stage (P = .066) and higher grade (P = .025). This study shows that DNA-ploidy and SPF measured on a single superficial bladder cancer specimen are not predictive of tumor recurrence. The frequent multifocality of the disease may explain, in part, these findings.

Prevalence and clinical significance of HER/2neu, p53 and Rb expression in primary superficial bladder cancer.

PURPOSE: The usefulness of the expression of HER2/neu oncoprotein and of p53 and Rb suppressor gene product as predictors of tumor recurrence was evaluated by using a bank of prospectively collected primary papillary bladder tumors treated initially only by transurethral resection. MATERIALS AND METHODS: The expression of HER-2/neu oncoprotein and p53 and Rb suppressor genes was evaluated by immunohistochemistry in 256, 265 and 74 specimens of primary Ta/T1 superficial bladder tumors obtained from patients enrolled in a prospective study from 1990 to 1992. Survival analysis was used to evaluate the association between time to first recurrence and expression of each marker, the follow-up period extending to March 1994. Immunostaining for p53 and HER-2/neu was performed on paraffin-embedded tissue and, for Rb, on frozen tissue only. RESULTS: Her-2/neu was expressed in 21 (8.2%) cases and p53 in 39 cases (14.7%); Rb expression was altered in 12 (16.2%). In this study, p53 expression was only related to earlier recurrence in a univariate analysis. Multivariate analysis, however, failed to recognize p53 expression as an independent predictor of recurrence. CONCLUSIONS: Our study demonstrates the low prevalence of HER2/neu, p53 and altered Rb expression in superficial TCC at initial resection. Only p53 expression was significantly associated with an earlier first tumor recurrence, but this association was not independent of other prognostic factors.

Prognostic significance of cathepsin-D expression in node-positive breast carcinoma: an immunohistochemical study.

The prognostic significance of cathepsin-D expression was evaluated by immunohistochemistry in 638 node-positive breast carcinomas diagnosed between 1980 and 1986. A minimum of 2.5 years of follow-up was available for each patient (maximum: 9.5 years). Cathepsin-D expression was assessed separately both in cancer and in stromal cells using a commercially available polyclonal antibody. While cancer-cell immunostaining was not associated with prognosis, positive staining of stromal elements was related to shorter metastasis-free survival. The difference in distant metastasis-free survival between positive and negative expressors was greatest in the sub-group of patients submitted to adjuvant chemotherapy, with a hazard ratio for occurrence of distant metastasis of 1.76 by multivariate analysis, but was lowest for those receiving hormone therapy. Cathepsin-D expression by stromal cells was related to HER-2/neu oncoprotein expression, HSP-27 expression, poor nuclear grade, aneuploidy, and absence of estrogen and progesterone receptors. No association was found with the number of involved lymph nodes, tumor size, age, histologic grade, S-phase fraction, or vascular invasion. Our study suggests that cathepsin-D expression by stromal cells (and not by cancer cells) affects the prognosis of breast cancer, that stromal cells probably play a key role in local invasion and metastatic dissemination of the tumor, and that the prognostic significance of cathepsin-D expression may vary according to the type of adjuvant therapy.

Effects of reducing physical therapy services on outcomes in total joint arthroplasty.

A natural experiment provided an opportunity to determine whether physical therapy (PT) service reduction would affect the outcomes of total joint arthroplasty. A sample of 200 patients with rheumatoid arthritis or osteoarthritis who underwent total hip or total knee replacement during successive reduction of services was randomly selected. The demographic and clinical characteristics of patients in each period were similar. Despite large differences between groups in hours of PT per patient, there were no major differences in length of stay between the groups, or compared to similar hospitals, functional status at discharge, or numbers of surgical complications. Implications for health services organization are discussed.