Our retrospective analysis has identified protease expression and tumor cell proliferation rate as important biological prognostic factors in breast cancer. Prospective clinical trials should be undertaken to confirm these results.

Objective To determine the value of serum chromogranin A (CgA), a marker of neuroendocrine differentiation, for monitoring prostate cancer; CgA levels were related to three other tumour markers, i.e. total prostate‐specific antigen (tPSA), prostatic acid phosphatase (PAP), neurone‐specific enolase (NSE), and to testosterone, to assess the importance of hormone withdrawal. Patients and methods Serum samples (218) were obtained from 118 patients with prostate cancer, including 111 patients with advanced prostate cancer; 103 presented to our centre for systemic radionuclide therapy of painful skeletal metastases. CgA concentrations were measured using a new immunoradiometric assay (IRMA; Cis Bio International, Gif sur Yvette, France) and a threshold of 70 ng/mL was determined after receiver operating characteristic curve analysis. Testosterone was also measured with an IRMA assay; tPSA, PAP and NSE were assayed using the time‐resolved amplified cryptate emission. Results Serum marker levels were high in 64% of the patients for CgA, 24% for NSE, 89% for tPSA and 81% for PAP. Patients resistant to endocrine treatments and with elevated tPSA (i.e. hormone‐independent) showed increased CgA and NSE in 62% and 29%, respectively. Patients with hormone‐dependent prostate cancer (i.e. with a normal tPSA level) had elevated CgA in 59% but no abnormal NSE. All patients of the latter group except one showed clinical progression of their disease. However, the mean (sd) concentrations of CgA in hormone‐independent (146) or hormone‐dependent (22) patients, at 185.3 (449.1) and 160.9 (293.9) ng/mL, respectively, were not statistically different (P = 0.8, Mann–Whitney U‐test). For 30 patients, blood samples were drawn and markers measured before and after systemic radionuclide therapy. There was a significant increase in the CgA and tPSA concentrations after treatment (P = 0.0146 and 0.0025, respectively). Conclusions In association with tPSA, serum CgA appears to be a promising marker for monitoring patients with prostate cancer.

BACKGROUND Cell proliferation is a major determinant of the biologic behavior of breast carcinoma. MIB‐1 monoclonal antibody is a promising tool for determining cell proliferation on routine histologic material. The objectives of this study were to compare MIB‐1 evaluation to other methods of measuring cell proliferation, with a view to refining the cutoff used to classify tumors with low and high proliferation rates in therapeutic trials. METHODS One hundred eighty‐five invasive breast carcinomas were evaluated for cell proliferation by determining monoclonal antibody MIB‐1 staining, histologic parameters (Scarff–Bloom–Richardson grade and mitotic index) on paraffin sections, S‐phase fraction (SPF) by flow cytometry, and thymidine‐kinase (TK) content of frozen samples. RESULTS There was a high correlation (P = 0.0001) between the percentage of MIB‐1 positive tumor cells and SPF, TK, histologic grade, and the mitotic index. Multivariate analyses including MIB‐1 at 5 different cutoffs (10%, 15%, 17% [median], 20%, 25%) and the other proliferative markers showed that the optimal MIB‐1 cutoff was 25% and that the mitotic index was the proliferative variable that best discriminated between low and high MIB‐1 samples. A MIB‐1 cutoff of 25% adequately identified highly proliferative tumors. Conversely, with a MIB‐1 cutoff of 10%, few tumors with low proliferation were misclassified. CONCLUSIONS The choice of MIB‐1 cutoff depends on the following clinical objective: if MIB‐1 is used to exclude patients with slowly proliferating tumors from chemotherapeutic protocols, a cutoff of 10% will help to avoid overtreatment. In contrast, if MIB‐1 is used to identify patients sensitive to chemotherapy protocols, it is preferable to set the cutoff at 25%. The MIB‐1 index should be combined with some other routinely used proliferative markers, such as the mitotic index. Cancer 2002;94:2151–9. © 2002 American Cancer Society. DOI 10.1002/cncr.10458

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Background: S-phase fraction (SPF) measurement by flow cytometry is a clinically useful prognostic factor in patients with breast carcinoma. Standardized SPF determination is essential. As part of a multicenter study, we evaluated the influence of the choice of software and histogram resolution (256, 512, or 1,024 channels) on SPF quantification. Methods: One hundred thirty-three DNA histograms were analyzed in three laboratories with Modfit 5.2, Modfit LT, and Multicycle AV software. Strict rules for histogram interpretation and software management were applied. The following five options were compared: MF 5.2 1024, MF 5.2 256, MF LT 256, MC AV 256, and MC AV 512. Results: In the DNA diploid and aneuploid groups, SPF distributions were not statistically different among the five