Assessment of proliferative activity by anti-PCNA monoclonal antibodies in formalin-fixed, paraffin-embedded samples and correlation with mitotic index.
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Biomedical subjects
Publications and source records attributed to R Preziosi.
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The recent availability of monoclonal antibodies raised against cell cycle nuclear antigens makes possible, by means of immunohistochemical techniques, an easy and quick method of evaluating tumour kinetic activity, in addition to older methods such as measurement of the mitotic index. Some of these antibodies can be used on formalin-fixed paraffin wax-embedded samples, thus allowing the use of archival material. In the present study the proliferative activity of testicular tumours of the dog (seminomas and Sertoli and Leydig cell tumours) was investigated with two monoclonal antibodies to proliferating cell nuclear antigen (PCNA) clone PC10, and Ki67 clone MIB1. The former recognizes a formalin-resistant epitope of PCNA, and MIB1 the same antigen as Ki67 in formalin-fixed, paraffin wax-embedded sections after incubation in a microwave oven. Three parameters of proliferative activity were considered: PCNA and Ki67 indices (percentage of nuclear area positive to PCNA and to Ki67), and mitotic index (number of mitoses per 1000 cells). The PCNA index and Ki67 index revealed a good correlation in linear regression analysis (P < 0.001) as did the mitotic index (P < 0.01). None of the parameters considered revealed a significant difference in proliferative activity of the three types of tumour (P > 0.05-Spearman test), but in both seminomas and Sertoli cell tumours the progression from tubular to diffuse pattern paralleled an increase in growth fraction. It is interesting that some seminomas of the diffuse type, often considered on histological grounds to be the most malignant, showed the highest values of the above-mentioned parameters.
In order to verify the relative role of each single risk factor during a long period of observation, and to compare the frequency of risk factors in parenterally and non-parenterally transmitted acute viral hepatitis, we studied 1,251 patients admitted to our Department from 1971 to 1991. Acute hepatitis A cases were considered non-parenterally transmitted, whereas B, C, NANB and Delta hepatitis were grouped together as parenterally transmitted. The two groups were compared for age, sex and the following risk factors: surgical procedures, transfusion, dental procedures, intravenous drug addiction, infected partner, infected relative and hospital admission. There were 243 non-parenterally transmitted and 1,008 parenterally transmitted cases. In univariate analysis, mean age in the two groups was 20 and 37 years (p = 0.000001) for non-parenterally and parenterally transmitted cases respectively; mean ages of patients with different parenterally transmitted hepatitis (B, NANB, C, Delta) did not differ significantly (p = 0.35). The following risk factors were significantly more frequent in the parenterally transmitted hepatitis group: surgical procedure (odds ratio = 8.04, 95% confidence intervals: 3.75, 20.51), transfusion (OR = 18.79, 95% CI: 5.03, 157.72), dental procedures (OR = 2.19, 95% CI: 1.2, 4.06), drug addiction (OR: 11.02, 95% CI: 4.15, 41.34), and infected partner (OR = 17.61, CI: 3.02, 708.65). However, logistic regression showed the following factors as being significant: age (p = 0.00001), transfusion (OR = 3.35, 95% CI: 1.61, 6.94), dental procedures (OR = 1.61, 95% CI: 1.18, 2.2), drug addiction (OR = 4.88, 95% CI: 2.94, 8.1).(ABSTRACT TRUNCATED AT 250 WORDS)
The biological behaviour of canine cutaneous mast cell tumours (MCTs) is highly variable. The aim of this study was to investigate whether intratumoral microvessel density (IMVD), as an indicator of angiogenesis, was predictive of biological behaviour in MCTs of canine skin, and to relate this parameter to histological grade and other histomorphological features. IMVD was evaluated by immunohistochemical labelling of the endothelial marker factor VIII (Von Willebrand's factor)-related antigen in 32 primary cutaneous MCTs. Computer image analysis was used to measure IMVD, expressed as the number of microvessels per square millimetre. Cases were assigned to low and high vessel density groups, the median value (14.1) being used as the "cut-off". Kaplan-Meier-estimated survival curves of the groups revealed that IMVD was significantly associated with survival time (P=0.046). One-way analysis of variance, performed to compare the IMVD values of tumours of different histological grades, showed a significant difference between grades I and III (P=0.0002). There was a significant difference in IMVD between moderately invasive and highly invasive tumours (P=0.002) and between tumours with different numbers of mitoses (P=0.0046). In multivariate analysis, performed to test the combined influence on survival of each parameter, only the mitotic index and IMVD were independent prognostic variables (P=0.00019). The relation of angiogenesis to biological behaviour and histological parameters of malignancy of cutaneous MCTs was consistent with previous findings in human and animal tumours.
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