The cell-cycle inhibitor p27 is a potential tumor suppressor, but its gene has never been found inactivated in human tumors. Because cell-cycle regulation of p27 cellular abundance occurs at the post-transcriptional level, we analyzed p27 protein expression and degradation in human colorectal carcinomas. Proteasome-mediated degradation activity of p27 was compared with its protein levels in a subset of tumor samples. We found that carcinomas with low or absent p27 protein displayed enhanced proteolytic activity specific for p27, suggesting that low p27 expression can result from increased proteasome-mediated degradation rather than altered gene expression. Patients whose tumors expressed p27 had a median survival of 151 months, whereas patients who lacked p27 (10%) had a median survival of 69 months. By multivariate analysis, p27 was found to be an independent prognostic marker. Lack of p27 was associated with poor prognosis (2.9 risk ratio for death; P = 0.003). The absence of p27 protein expression is thus a powerful negative prognostic marker in colorectal carcinomas, particularly in stage II tumors, and thereby may help in the selection of patients who will benefit from adjuvant therapy. These data suggest that aggressive tumors may result from the selection of a clone or clones that lack p27 due to increased proteasome-mediated degradation.

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BACKGROUND: Circulating tumour cells (CTCs) offer a non-invasive approach to obtain and characterise metastatic tumour cells, but their usefulness has been limited by low CTC yields from conventional isolation methods. METHODS: To improve CTC yields and facilitate their molecular characterisation we compared the Food and Drug Administrationapproved CellSearch Epithelial Kit (CEK) to a simplified CTC capture method, CellSearch Profile Kit (CPK), on paired blood samples from patients with metastatic breast (n ¼ 75) and lung (n ¼ 71) cancer. Molecular markers including Human Epidermal growth factor Receptor 2 (HER2) were evaluated on CTCs by fluorescence in situ hybridisation (FISH) and compared to patients' primary and metastatic cancer. RESULTS: The median cell count from patients with breast cancer using the CPK was 117 vs 4 for CEK (Po0.0001). Lung cancer samples were similar; CPK: 145 cells vs CEK:4 cells (Po0.0001). Recovered CTCs were relatively pure (60 -70%) and were evaluable by FISH and immunofluorescence. A total of 10 of 30 (33%) breast cancer patients with HER2-negative primary and metastatic tissue had HER2-amplified CTCs. CONCLUSION: The CPK method provides a high yield of relatively pure CTCs, facilitating their molecular characterisation. Circulating tumour cells obtained using CPK technology demonstrate that significant discordance exists between HER2 amplification of a patient's CTCs and that of the primary and metastatic tumour.

The clinical features and response to treatment of 35 patients (pts) with extramedullary plasmacytoma (EMP) were retrospectively analysed. The median age at diagnosis was 49 years (28-72). Twenty-two pts (63%) had stage I disease (localized to the primary site) 12 of whom (34%) had stage I-E (locally extended). Three pts (9%) had stage II (regional lymph nodes involved) and 10 (29%) stage III (disseminated disease). In locoregional disease (stages I, I-E, II) complete local control was achieved in 22 of 25 pts (88%), while in diffuse disease (stage III) complete remission (CR) was obtained in 5 of 10 pts (50%) (p = 0.05). In 9 of 18 pts treated with surgery, local control was achieved, and in 8 of the 9 patients with incomplete resection local control was obtained with additional radiation and/or chemotherapy. In 8 (66%) of the 12 pts treated with radiation complete local control was achieved. In 11 (58%) of 19 pts evaluable for initial chemotherapy CR was obtained. Three of these pts were treated with chemotherapy only and were alive and disease-free after a minimum follow-up of 8 years. The median time to relapse in local disease was 48 months versus 13 in disseminated disease. For pts with local disease the median survival time was 114 months and for disseminated disease 16 months (p = 0.0000). We conclude that in stage I chemotherapy is curative per se. In local stages (I, I-E and II) adjuvant chemotherapy should be considered, while in stage III only palliative therapy is feasible.