Mitotic activity should be recorded as an average of more than 10 hours per day (i.e., using the 40x objective on most conventionally configured microscopes). A sufficient number of fields should be counted in order to calculate a statistically meaningful average. In most cases, 30 hpf is sufficient, although 50 or more hpf may be required on occasion.
The normal human breast has approximately 600-1000 epithelial cells in each square millimeter. At puberty, the number of epithelial cells increases to about 3000 per square millimeter. After menopause, the number of epithelial cells decreases again to about 1000 per square millimeter.
In general, the higher the mitotic rate, the greater the risk of cancer development. However, this relationship does not apply to all types of cancers; for example, increased rates of proliferation are seen in skin lesions such as melanomas but not sarcomas such as fibrosarcomas. Also, some cancer treatments (such as radiation therapy) can increase the rate of cell division and thus promote tumor growth. Finally, some types of cancer have been shown to undergo endoreplication (the production of polyploid cells), which could account for increased numbers of mitotic figures if no further division occurs.
It is important to recognize that elevated levels of mitosis do not always indicate cancer. For example, high levels of mitosis can be found in benign tumors such as lipomas and sebaceous cysts.
The mitotic count is most commonly calculated in veterinary pathology, generally at 400x magnification, however the area counted is seldom described, and the mitotic index is the phrase most commonly reported. The mitotic index is calculated by dividing the number of cells undergoing mitosis by the number of cells not undergoing mitosis. Thus, a value of 1 means that 100% of the cells are undergoing division, while a value of 0.1 means that 10% of the cells are undergoing division.
In human medicine, the term "mitotic count" usually refers to the total number of mitoses observed in a microscope field (usually 1000 cells) during a routine examination of tissue samples taken during surgery or biopsy for diagnostic purposes. Reporting the percentage of cells in mitosis would be expected from a sample with a high proportion of cells in various stages of division.
A mitotic count can also be performed on body fluids such as blood or urine. This is useful in patients where tissue sampling is difficult or impossible, for example, due to bleeding or fatality. The mitotic count in these cases gives an indication of how rapidly cancer cells are dividing and so indicates how likely it is that the patient will respond to treatment.
Cancers with a high mitotic rate tend to be more aggressive than those with a low mitotic rate. For example, cancers with a high mitotic rate tend to spread more widely through the body and are more likely to return after they have been treated.
The mitotic rate has a significant prognostic value. A rate more than 6/mm2 was assumed to be a significant level at first, however Azzola et al. discovered that there were no significant survival differences for stepwise increases in mitotic activity beyond 1 mitosis/mm2. Therefore, they suggested that a threshold of 12 mitoses/mm2 should be used to define high-grade prostatic cancer.
The Gleason score is also important for predicting outcome after surgery or radiation therapy. Patients with scores of 7 or higher usually have a poor outcome after treatment; patients with lower scores often show response to therapy.
Immunohistochemical markers can also help predict outcome. For example, patients whose tumors express PSMA are more likely to have recurrent disease if they undergo prostatectomy. In addition, researchers have found that patients who do not express PSMA after surgery may still respond to other treatments such as abiraterone acetate (Zytiga) and enzalutamide (Xtandi).
Finally, genetic markers can also help predict outcome. For example, patients with mutations in DNA repair genes are more likely to have recurrent disease after surgery or radiation therapy.