Pavelic Zp

Absence of Retinoblastoma gene product in human primary oral cavity carcinoma

Oral cavity cancer is a major health concern worldwide. Despite advances in surgery, radiotherapy and chemotherapy over the past 35 years, there has been no significant enhancement in the survival of oral cavity cancer patients. Improved survival will require identification of reliable prognostic markers that provide a rational basis for assessment of risk for progression. The altered retinoblastoma (RB) gene has been linked to the hereditary retinoblastoma. This gene is defective in several types of human malignancies. The intent of this study was to evaluate the role of the RB gene in oral cavity tumorigenesis and to explore whether or not there is a relationship between the loss of RB protein and each of several clinicopathological parameters in oral cavity carcinomas. We have analysed the expression of the RB gene in four cell lines (J82, ML1, SaOS2 and WERI-RB-1), 182 oral cavity carcinomas (75 T1 and 107 T3 and T4 lesions) and 55 normal tissues adjacent to cancer by means of an immunohistochemical method and Western immunoblotting. The expression of RB protein was then correlated with clinical outcome in the patients with primary tumours. The significantly higher rate of altered RB expression was found in advanced oral cavity tumours (40 of 107; 37%) in comparison with low grade tumours (9 of 75; 7%). In T3 and T4 tumours, RB gene expression did not correlate with presence or absence of lymph node metastasis, degree of differentiation and patient survival. However, in the T1 cohort, poorer survival rate was seen for those patients who had a tumour with loss of RB protein. This study suggests that tumours in which the RB protein was altered were more aggressive than tumours in which the RB protein was present and that loss of RB protein in oral cavity cancer may be a prognostic variable of tumour progression.

Studies of the geographic patterns of c-myc expression in bone marrow

Abstract. C‐myc expression was studied semi‐quantitatively in bone marrow biopsies obtained from normal individuals, patients with non‐malignant haematological disorders and patients with various haematological malignancies. In normal bone marrow and in the bone marrow of patients with non‐malignant haematological disorders, cells containing c‐myc protein are present in small clones (average 7 ± 2·5 cells/clone) located in the centre of the histotopographic region of the biopsy. In contrast, c‐myc‐containing cells are diffusely distributed in the bone marrow of patients with acute myelogenous leukaemia (AML). In the marrow of patients with myelodysplastic syndromes evolving to AML and in patients with AML in early relapse, the clones of cells containing c‐myc are larger than those present in normal marrows (average clone size = 17·5 ± 3·5 cells). Additionally, the proportion of the cells in normal bone marrow which express c‐myc protein is less than that present in AML marrows (23·3 ± 10·17 v. 60·2 ± 6·17) and the intensity of staining is also less. Non‐Hodgkins lymphoma patients with bone marrow involvement had distribution of c‐myc positive cells similar to those with leukaemic infiltration.

Overexpression of glutathione S-transferase pi messenger RNA and its relationship to gene amplification in head and neck squamous cell carcinoma

Human glutathione S-transferase pi has been known to be a good marker for several tumor types because of the high frequency with which it is overexpressed. In order to determine whether GST pi is useful as an indicator for head and neck cancers, expression of GST pi was investigated by Northern analysis. Overexpression of mRNA was detected in 9 of 36 primary head and neck squamous cell carcinomas. To examine the relationship between overexpression and amplification of GST pi gene, Southern analysis was performed on all samples. Only 3 of the 36 tumors showed amplification GST pi genes, indicating that gene amplification may not play a key role in GST pi mRNA overexpression in these cancers.