PHH3, Ki-67 and Mitotic Count Correlation in Adrenal Cortical Carcinoma
Ricardo R Lastra, Stephen R Master, Michael D Feldman, Timothy Baradet, Amy Ziober, Zhanyong Bing. Hospital of the University of Pennsylvania, Philadelphia, PA
Background: Adrenal cortical carcinoma is an aggressive, uncommon neoplasm and the diagnosis can be challenging in small lesions confined to the adrenal gland. Scoring methods utilizing criteria such as nuclear grade, mitotic count, growth pattern, necrosis and vascular/capsular invasion have been proposed to aid in the diagnosis. Ki-67 proliferation index of over 5% favors a malignant diagnosis. Phosphohistone H3 (pHH3) is an immunohistochemical marker recently used to evaluate the proliferation index of tumors such as melanoma and urologic malignancies. In this study, we evaluate the correlation between PHH3, Ki-67 and mitotic count in adrenal cortical carcinomas to assess its utility in the evaluation of these cases.
Design: A database search for cases of adrenal cortical carcinoma was performed (1991-2010). On each case, a hematoxylin and eosin (H&E) stained slide was obtained and immunohistochemical (IHC) stains for Ki-67 (clone MIB-1; 1:20 dilution, Dako M7240) and pHH3 (polyclonal; 1:25 dilution, Cell Marque 369A) were performed. Mitotic count was performed on 50 high-power fields (HPF) on the H&E slides. IHC slides were analyzed by digital image analysis software (InForm, Caliper Life Sciences) and percent nuclear positivity was recorded. Pearson test of correlation significance was performed using the R statistical package.
Results: Fifteen cases (n=15) were analyzed in this study (14 primary tumors and one metastatic tumor). Patient age ranged from 29 to 77 years (mean 51 years). The mitotic count ranged from 5 to 73 mitosis per 50 HPF (mean 26 mitosis/50 HPF). pHH3 positivity ranged from 0.1% to 4.2% (mean 1.2%) and Ki-67 positivity ranged from 0.94% to 76% (mean 13.2%). pHH3 IHC positivity was seen only in nuclei of cells in M phase of the cell cycle, while Ki-67 positivity was seen also in cells not actively undergoing mitosis. Statistical analysis revealed a significant correlation between mitosic count and pHH3 positivity (0.67; 95% CI 0.27-0.88) (p=0.006) and between pHH3 positivity and Ki-67 positivity (0.70; 95% CI 0.29-0.89) (p=0.004). No statistically significant correlation was noted between mitotic count and Ki-67 positivity (0.33; 95% CI 0.21-0.72) (p=0.223).
Conclusions: Our study shows a direct correlation between mitotic count and pHH3 positivity. Since mitotic count is one of the main criteria for diagnosing adrenal cortical carcinoma, these findings support the use of pHH3 IHC in the evaluation of adrenal cortical tumors, in particular the more challenging cases. Furthermore, the use of pHH3 IHC facilitates the mitotic count in these cases.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 84, Monday Morning