Estimation of the proliferative activity of human breast cancer tissue by means of the Ki-67 and MIB-1 antibodies--comparative studies on frozen and paraffin sections.

The estimation of the Ki-67 index in human breast cancer tissue has been proven to be a useful prognostic tool. The examination can be performed, however, only on frozen sections (FS). The development of an antibody directed against parts of the Ki-67 antigen (MIB-1) has opened a new route to determine the proliferative activity on paraffin sections (PS). MIB-1 immunohistochemistry is used instead of Ki-67 immunohistochemistry if a tumour is delivered to the pathologist after formalin fixation or if that part of the tissue suspicious for breast cancer must be totally embedded in order to confirm the diagnosis. The present study compares the findings of Ki-67 (FS) and MIB-1 (FS and PS) immunohistochemistry in a total of 544 cases of human breast cancer. The findings confirm a good statistical correlation between the Ki-67 and the MIB-1 findings. The MIB-1 results are 2-2.5 times higher in FS than in PS. Good agreement exists between the Ki-67 indices determined on FS and the MIB-1 indices determined on PS. If the cut-off value for the separation of Ki-67 negative and positive cases is defined as 10%-20%, a MIB-1 index in PS of 10% permits the correct prediction of a negative Ki-67 index in 97% of the cases, and a MIB-1 index of 30% or more correctly predicts a positive Ki-67 index in 90% or more of the cases. Hence, the determination of the MIB-1 index on PS may replace the determination of the Ki-67 index on FS with a high degree of probability.

Comparative evaluation of p53-protein expression and the PCNA and Ki-67 proliferating cell indices in human astrocytomas.

Mutations of the p53 gene are one of the most frequent genomic alterations of human tumours of astrocytic lineage. Because the physiological role of this gene is a suppression of cellular proliferation and growth, the overexpression of p53-protein may correlate with the expression of PCNA or Ki-67, established markers of cell proliferation. Paraffin-embedded surgical specimens from 60 human astrocytomas (9 pilocytic tumours, 12 WHO grade II, 9 anaplastic astrocytomas [WHO grade III] and 30 glioblastomas [WHO grade IV]) were stained with anti-PCNA (PC10), anti-p53(DO-7) and anti-Ki-67 antibodies (DAKO). Approximately 40% of all the cases were p53-protein immunopositive (53.3% glioblastomas, 33.3% anaplastic, 41.7% low grade astrocytomas but no pilocytic tumor). Statistical analysis did not reveal statistically significant correlation between p53-immunopositivity and PCNA or Ki-67 labeling indices. The Ki-67- and PCNA LI-s were statistically correlated, and the former better discriminated groups of different grades of malignancy.

Proliferative potentials of glioma cells and vascular components determined with monoclonal antibody MIB-1.

Proliferative activity in 78 glioma specimens was assessed immunohistochemically by determining proliferating index of tumor cells (PTC-PI) and endothelial cells (PEC-PI) using the MIB-1 monoclonal antibody. The PTC-PI of anaplastic astrocytoma (9.0 +/- 5.8: mean +/- standard deviation) was significantly higher than that of astrocytoma (1.2 +/- 0.4, < 0.01), and lower than that of glioblastoma multiforme (12.0 +/- 5.6, < 0.05). We then compared PTC-PI values, patients' age and extent of tumor resection with the prognosis of patients with malignant glioma (both glioblastoma and anaplastic astrocytoma). Kaplan-Meier survival rate analysis demonstrated higher survival rates in patients with less than 8.0% of PTC-PI at 5 and 10 years (p < 0.05). The mean age of patients who survived more than a year was lower than that of patients who died within a year (53.0 y.o., vs. 59.7 y.o., p < 0.01). Total or subtotal resection of the tumor was more often performed in the former than latter patients (51% vs. 21%, p < 0.01). These results suggested PTC-PI provides useful information which may allow better assessment of the biological behavior and clinical prognosis of glioma, in addition to histological grading, patients' age and extent of tumor resection. While the average PEC-PI value (3.3) was lower than that of PTC-PI (7.0), there was a significantly close relationship between PTC- and PEC values (p < 0.01), providing an impetus to develop novel therapies directed toward suppression of microvascular regeneration.

Laminin expression in testicular tumours of the dog.

The expression of laminin was studied to determine the distribution pattern of basement membranes (BMs) in normal testes and in a series of 40 canine testicular tumours (seminomas, Leydig and Sertoli cell tumours). BM was always present around seminiferous tubules and blood vessels in normal testes and in seminomas and Sertoli cell tumours of the intratubular type without invasion. BM changes (fragmentation or loss, or both) were usually found in invasive neoplasms which retained their tubular structure; disruption or absence was observed in tumours, with a diffuse pattern. The BM was never expressed in Leydig cell tumours, except around vessels, irrespective of their histological growth pattern (cystic-vascular, pseudoadenomatous, diffuse). An attempt was made to relate the degree of BM modification to proliferative monoclonal antibodies and mitotic index. In parallel with the progressive loss of BM an increase in proliferative activity occurred, indicating that BM changes are additional useful prognostic indicators in testicular tumours of the dog.

Estudio comparativo de tres modelos de melanomas murinos Harding-Passey, B16 y B 16F 10 / Comparative study of three murine melanoma models: Harding-Passey, B16 and B16F10

Planteamiento: Estudiamos las características clinicopatológicas, ultraestructurales y el comportamiento biológico de tres líneas de melanomas murinos: Harding-Passey. B16 y B16F10. Material y métodos: Se han utilizado 80 ratones C57B1/6J, a los que se inyectó una suspensión de 10° células tumorales por vía subcutánea a nivel inguinal. Se procesaron muestras de los tumores para el estudio microscópico óptico y electrónico. Se realizó el estudio estadístico. Resultados: Las tres líneas originaban tumores fácilmente trasplantables. De los tres modelos, el Harding-Passey supone el tumor de crecimiento más lento, presentando los menores pesos medios, el menor índice mitótico y una supervivencia mayor de los animales huéspedes. El B16 muestra un crecimiento intermedio con pesos tumorales de casi el doble que el anterior, un índice mitótico ligeramente superior y una supervivencia de los ratones ligeramente inferior. El B16F10 muestra la mayor capacidad de crecimiento, siendo los pesos medios de los tumores seis y cuatro veces mayores, respectivamente, que los de Harding-Passey y B16, con un índice mitótico más alto y una supervivencia de los animales inferior a la mitad de los anteriores. Conclusiones: Las tres líneas estudiadas constituyen modelos experimentales idóneos para el estudio del melanoma. Los tumores muestran un comportamiento biológico distinto, con una capacidad proliferativa variable, siendo el B16F10 el de mayor crecimiento. La baja supervivencia de los animales hace que sea un modelo ideal para estudios cortos. Todos mostraban alteraciones en la ultraestructura de los melanosomas (AU)