Diffuse malignant mesothelioma of the peritoneum is a rare diagnosis. Despite many histopathologic similarities between peritoneal and pleural tumors, clinical and prognostic features may be quite different. There is a paucity of data evaluating molecular features of peritoneal mesotheliomas. Therefore, we compared the results of a battery of immunohistochemical markers, some with therapeutic implications, in patients with primary peritoneal or pleural mesotheliomas. We examined 24 peritoneal and nine pleural malignant mesotheliomas with a battery of immunohistochemical markers (cytokeratin AE1/3, calretinin, c-kit/CD117, desmin, epidermal growth factor receptor (EGFR), estrogen receptors (ER), progesterone receptors (PR), MIB-1, and cleaved caspase-3) in an attempt to distinguish any differences in this tumor arising in these two distinct locations. The results indicate that the only marker to show a significant difference in its staining pattern between these two sites was EGFR (P ¼ 0.0004). In all, 92% (22/24) of peritoneal tumors demonstrated 3 þ or 4 þ immunoreactivity with EGFR, opposed to only 33% (3/9) pleural tumors. There was no significant difference in immunoreactivity between the pleural and peritoneal tumors with c-kit, ER, PR, cleaved caspase 3, calretinin, and desmin. There was a trend toward increased cytokeratin (P ¼ 0.07) and MIB-1 (P ¼ 0.08) expression in the peritoneal group. There was no significant difference in age, sex, or histologic subtype between the two locations. In conclusion, despite similarities between peritoneal and pleural mesothelioma, there are differences between this neoplasm arising in these two sites. The EGFR expression is more pronounced in peritoneal tumors compared to pleural tumors. The increased expression of EGFR in the peritoneal lesions may be of clinical significance with the recent emergence of epidermal growth factor receptor-targeted therapies.

Compared with the parent cell line, we did observe a dose-dependent decrease in growth factor-stimulated motility and a decrease in metastatic potential in two clones with four-and eighffold elevated nm23-H1 expression, whereas the proliferative activities were similar. We conclude that the decreased metastatic potential might be related to down-regulation of growth factor-stimulated motility.

Background: Despite years of research, it is still unclear which women with node-negative (N-) breast cancer will need adjuvant chemotherapy and which women are being treated unnecessarily. Our goal was to determine which factors best predicted disease free survival (DFS) or cancer-specific overall survival (OS) and, therefore, select the correct patients for treatment. A total of 11 parameters were measured: estrogen receptor (ER), progesterone receptor (PR), age, race, ploidy status, %G0/G1 (% non-DNA synthesis), %S (% S-phase), cathepsin D status, size, stage, and histologic grade.Results: In this prospective study, we followed 556 N-patients diagnosed between 1991 and 1996. The tumors were 56% ER؉, 51% PR؉, 30% diploid, with a mean %S of 8.9%. The level of cathepsin D ranged from 0.50 to 155 pmol/mg of protein with a mean of 42.9 pmol/mg of protein. There were 87 recurrences (16%) and 72 cancer deaths (13%), with a median follow-up of 7.8 years. Ploidy status (p ‫؍‬ 0.01), S-phase activity (p ‫؍‬ 0.003), G1 phase activity (p ‫؍‬ 0.02) and age (p ‫؍‬ 0.01) were able to significantly predict DFS in a univariate manner. All of the measurable factors were significant or borderline significant in predicting OS in a univariate manner except for age, race, and ER status. In multivariate analysis with S-phase included, it was the only remaining factor in DFS and OS; with S-phase excluded, age and ploidy status remained as factors for DFS in stepwise regression, while PR, size, and cathepsin D were the remaining factors that predicted cancer-specific OS. The effect of adjuvant treatment on prognosis was also analyzed.Conclusions: Both biochemical and clinical parameters have the potential to predict prognosis for Nbreast cancer. In this large prospective clinical trial, with a median follow-up of 7.8 years, no individual marker adequately predicted the prognosis for an individual patient. %S activity was the best independent marker, but only 77% of the tumors provided this value. Subset analysis provided improved prognostication, but there were limits to its utility. These data represents a definitive study starting in 1991 and ending in 2002.

This report describes a companion flow cytometry study (Cancer and Leukemia Group B (CALGB)-8869) using tumors derived from patients enrolled in a large randomized clinical trial (CALG6-8541) performed on 1,572 patients with early stage, node-positive breast cancer. The CALGB initiated an adjuvant breast cancer trial in 1985 to determine if dose intensification (dose of drug per unit time) of chemotherapy was related to relapse-free and overall survival. Patients were randomized by pretreatment clinical variables to one of three different dosage regimens of chemotherapy. Using a tumor enrichment procedure, 442 paraffinembedded blocks were analyzed by flow cytometry, and S-phase fraction (SPF) was analyzed by three different methods. Ploidy analysis was performed using standard procedures. Tissue from 90% of the patients was suitable for ploidy analysis, whereas only 68% could be assessed for SPF. With a median follow-up time of 80 months, our results show that ploidy status had no clinical utility, whereas high SPF predicted poorer overall survival. The rectangular fit model for SPF was more predictive of outcome than both the area fit model and a computer fit model (modfit) for SPF. In univariate analysis, patients with a low SPF (< 10%) had a better prognosis than those patients with a high SPF (> lo%), but they responded equally well to the different treatment regimens. Patients with high SPF (> 10%) had longer relapse-free and overall survival to high dose chemotherapy compared to low or standard dose chemotherapy. Multivariate analysis indicated that treatment intensity as well as the number of positive nodes, tumor size, steroid receptor status, and c-erb 8-2 expression were significant in predicting overall and disease-free survival. The multivariate analysis, however, revealed that SPF was significant in predicting overall but not diseasefree survival, but there was no longer any relationship among SPF, dose intensity, and outcome. Key terms: Flow cytometry, breast cancer, standardization, S-phase, prognosisThe use of flow cytometry analysis for determining prognosis in patients with early breast cancer depends on several different factors, including tissue preparation procedure, quality of the DNA histogram, methods of histogram analysis, patient characteristics, and treatment. Some reports indicate that DNA content (ploidy) and cell cycle kinetic (S-phase fraction, %S) data are useful in predicting outcome ( 1-3), whereas other reports have shown no predictive value for this information (4-6). A recent NIH consensus conference on breast cancer concluded that ploidy is of limited prognostic use, whereas S-phase fraction (SPF) has prognostic value if performed correctly (7). At the present time, and in spite of continuing controversy, many laboratories, both academic and commercial, are performing both ploidy and SPF on breast cancer tissues for clinical use.The CALGB initiated an adjuvant breast cancer protocol for node-positive patients in 1985 to determine if ~~~~~ ~

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