Mitotic index matter: how to improve the assessment of mitosis in order to better classify G2 breast cancer and luminal A category.

G2 ductal infiltrating carcinomas are a heterogeneous group of tumours with ambiguous clinical significance. This is because G2 carcinomas are almost always the largest category and poorly reproducible. Mitotic count (MC) is one of the causes of poor histological grading reproducibility. The phosphoistone H3 (PPH3) antibody improves identification of mitotic figures. The aim of our study is to demonstrate whether using a new histological grading system based on PPH3 immunostaining to assess MC can re-stratify G2 category. We selected 100 cases of G2 invasive carcinoma. The mitotic score was accurately re-evaluated performing MC on PPH3 immunostained sections. 21/100 G2 cases (21%) showed the same mitotic score both with hematoxilin and eosin (H&E) and PPH3 while 79 cases (79%) with PPH3 shifted to a higher mitotic score. After re-grading the 100 G2 cases based on the assessment of mitotic score with PPH3 only 53 cases (53%) were confirmed as G2, while 47 cases (47%) had shifted to G3. Finally we reclassified early tumours in the surrogate molecular subtype according to the 2013 St. Gallen Conference criteria and found that 13/40 cases (33%) classified as luminal A were G3 with the PPH3 mitotic score and could benefit from chemotherapy. In conclusion, PPH3 improving MC gives a better categorization by halving the G2 group. In particular, applied to the surrogate subtype luminal A breast cancer it identified cases that could benefit from adjuvant cytotoxic chemotherapy.