The value of phosphohistone H3 as a proliferation marker for evaluating invasive breast cancers : with an emphasis on comparisons to Ki-67

Abstract

NTRODUCTION

Ki-67 is a widely used marker of proliferation, but controversial due to problems of non-specificity and lack of reproducibility. In comparison, Phosphohistone H3 (PHH3) is specific marker for mitosis with good reproducibility. We compare the two markers using surgical slides of 220 breast cancer cases diagnosed from 2012 to 2013.

METHODS

The most representative sections of invasive breast cancer surgical cases were immunohistochemically stained for Ki-67 and PHH3.

RESULTS

Ki-67 and PHH3 had a good positive correlation between each other. PHH3 was tested for inter-rater agreement between two raters using two methods. First method was assessment under a microscope while the second method was assessment with taken photographs. Both demonstrated nearly perfect intra-class correlation coefficient (0.996, 0.977). PHH3 examined for 10HPF had a tendency to over-grade compared to H-E mitotic index (29 cases, evenly distributed). PHH3 examined at low power (objective 10x) correlated well with scores of 10HPF evidencing ability to accurately identify mitotically active areas(r = 0.999). Finally, PHH3 significantly correlated with recurrence-free survival (P = 0.006), while Ki-67 did not (P = 0.053).

CONCLUSION

The problems of Ki-67 for lack of reproducibility and low specificity to measure proliferation may be overcome by the use of PHH3 in diagnosis of breast cancer.