METHODOLOGIC ASPECTS OF A STANDARDIZED EV ALUATION OF MITOTIC-ACTIVITY IN TUMOR-TISSUES

Although estimation of mitotic activity is generally a recognized clin ical practice in the diagnosis and grading of tumors, there are severa l methodologic aspects that merit special consideration. Our results, in relation to those of others, lead to the following conclusions: 1. The values attained by calculating the mitotic activity of tumor cells in paraffin embedded tumor tissue are lower than those obtained in vi vo. The results cannot always be interpreted clinically due to the com plexity of some of the factors associated with it which require specia l attention. That the method still has clinical relevance and value in spite of the associated problems may be due to the fact that tumor ti ssues generally undergo long periods of hypoxia before being fixed for histomorphological analyses - a condition which by itself is a decisi ve factor in the reduction of mitotic activity - so that additional ch anges in some individual factors from case to case do not make much di fference to the estimated or calculated value. 2. Mitotic activity sho uld be calculated in areas of tumor sections where there are numerous mitotic tumor cells. Additionally, only cells with nuclei showing lyse d nuclear membranes and identifiable single chromosomes at higher magn ification ought to be considered in the calculation. Apoptotic and pyk notic elements should not be calculated. 3. The specification of the f inal magnification (e.g., x 400) is not a sufficient basis for compari son of optical conditions for the mitotic estimation, since the visual fields of standard light microscopes may differ up to 2.6-fold. A tem porary streamlining of the standard may be the application of a 0.159 mm(2) visual field (x 40 objective, x 10 ocular by visual field value 18). As an intermediate goal, mitotis should be calculated in percenta ges of the tumor cells or areas of the the total tumor tissue. 4. The interspecific reproducibility of the quantified mitosis makes it relia ble for clinical application. It compares well with cytometric and mor phometric methods in assessment of tumor cells and is of higher clinic al relevance than the conventional histomorphological tumor grading sy stems.