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Gliomas are malignant brain tumors thought to arise through multi-step tumorigenesis, involving both the activation of oncogenes and the loss of tumor suppressor genes. The cyclin D1 gene encodes a proto-oncogenic cell cycle regulator implicated in the pathogenesis of several types of cancer, including gliomas. Northern blot analysis revealed expression of cyclin D1 mRNA in 7 (47%) of 15 primary glioma specimens. Immunohistochemistry using an antibody specific for cyclin D1 showed strong positivity amongst neoplastic glial cells in the same glioma samples. No cyclin D1 mRNA or protein was detected in 5 normal brain specimens. Cyclin B, which has not been linked to tumorigenesis and serves as a marker for cellular proliferation, was expressed in all tumor, but not control, samples. These data provide the first evidence for the overexpression of cyclin D1 mRNA and protein in primary human gliomas, and are consistent with a proposed oncogenic role of cyclin D1 in these tumors. It is suggested that excessive levels of cyclin D1 with or without several other D-type cyclin proteins may lead to deregulation of G(1) control in subsets of human gliomas. These results are further discussed in the context of putative functional redundancy of D-type cyclins and the role of the D-type cyclin/p16-ink4/pRB pathway in tumorigenesis.

Gliomas are malignant brain tumors thought to arise through multi-step tumorigenesis, involving both the activation of oncogenes and the loss of tumor suppressor genes. The ros1 gene encodes a proto-oncogenic protein which has been implicated, by in vitro studies, in the pathogenesis of several types of cancer, including gliomas. Northern blot analysis revealed expression of ros1 mRNA in 3 (30%) of 10 primary glioma specimens. In situ hybridization localized ros1 mRNA transcripts to GFAP positive tumor cells and pericytes around capillaries. Immunohistochemistry using an antibody specific for ros1 demonstrated strong positivity amongst neoplastic glial cells in the same glioma samples. No ros1 mRNA or protein was detected in 5 normal brain specimens. These data provide the first evidence for the overexpression of ros1 mRNA and protein in primary human gliomas, and are consistent with a proposed oncogenic role of ros1 in these tumors.

p53 expression detected by immunocytochemistry is emerging as a novel potentially useful prognostic indicator in breast carcinoma. However, additional research is warranted because a consensus has not yet been achieved on: i) methodology and quality control issues; ii) its association with other new biological prognostic indicators; iii) its prognostic value in multivariate analysis including conventional and new pathobiological features and; iv) its clinical usefulness either as a prognostic and predictive factor. This study was undertaken in a series of 165 early-stage breast cancer patients (median follow-up of 5 years) to compare the prognostic role of p53 expression with that of several other markers that have been found to be of value, using a multivariate statistical analysis. These factors are: tumour angiogenesis, epidermal growth factor receptor (EGFR), c-erbB-2 expression, cathepsin D, growth fraction by Ki-67 antibody, DNA ploidy and S-phase fraction. The main results observed were: i) 47 of 165 (28.5%) carcinomas had pAb 1801 staining and were considered as p53-positive; ii) p53 expression was weakly associated with S-phase fraction by flow cytometry (OR=1.86; p=0.085); iii) p53 expression was significantly associated with recurrence (p53 negative [-] versus weak positive [+] tumours: p=0.07 and odds ratio of 2.21; p53 negative [-] versus high positive [++] tumours: p=0.01 and odds ratio of 2.86) and death (p53-versus +: p=0.53 and odds ratio of 1.35; p53- versus ++: p=0.05 and odds ratio of 2.53); iv) the determination of p53 is able to identify a subset of high risk patients in c-erbB-2 negative tumours, this group being generally considered at good prognosis; v) In multivariate analysis on relapse-free survival including all the above markers only tumour angiogenesis, cathepsin D, EGFR and S-phase fraction and nodal status retained significance, and for overall survival only tumour angiogenesis was significant and independent. This new information on p53 expression could be useful to the clinician for a more rationale approach in defining prognosis of breast cancer patients. The prognostic value of p53 depends on which other markers are additionally analyzed and previous studies have not always assayed tumour angiogenesis, which is the most important factor in this series. p53 still need to be assessed as a potential predictor of response to chemo or radiotherapy, because of its role in monitoring DNA damage.