P2.01-080 Mitosis Count of Lung Adenocarcinomas: Correlation between the Phosphorylated Histone 3, Number of Cancer Cells, Nuclear Grade, and Prognosis

Abstract

Nuclear grading can prognostically estimate inter-observer reproducibility in pulmonary adenocarcinoma (Nakazato Y. et al, Cancer, 2010 and JTO, 2013). However, no correlation has been shown between pathologic prognostic marker, number of cancer cells, and survival in pulmonary adenocarcinoma cases. Immunohistochemistry for phosphorylated histone 3 (pHH3), which is present during early prophase, is a reliable mitosis-specific marker. We evaluated the correlation between pHH3-stained mitotic figures (PHMFs) and clinical outcome, comparing the results with those of PHMFs, Ki-67 labeling index, and number of cancer cells. Primary tumors were obtained from 104 patients with pulmonary adenocarcinomas (≤2 cm maximum dimension) who were treated surgically between January 2006 and December 2010 at Dokkyo Medical University Hospital. Specimens were stained with hematoxylin and eosin and pHH3 and anti-Ki-67 antibodies. Cells were enumerated with a NanoZoomer® Digital Pathology. Results were evaluated using receiver operating characteristic (ROC) curve analysis, the Kaplan–Meier method and Cox proportional hazards regression. Cases judged negative by nuclear grading had significantly improved prognoses compared with positive cases (mean overall survival, 8.923 vs. 7.884 years; p=0.03). ROC curve analysis showed a cut-off of 400/10 hpf (area under the curve = 0.743; 95% CI = 0.594-0.891). Cancercell index, defined as the number of cancer cells within 10 hpf, of ≥400 tended to be positive, and of <400 tended to be negative. PHMF/cancercell index of ≥0.01 tended to be positive, and of <0.01 tended to be negative. PHMF/cancercell index (HR, 6.022), cancercell index (HR, 6.399), and lymphatic invasion (HR, 5.308) were correlated with prognosis (p<0.02). The number of cancer cells was correlated with Noguchi’s classification and WHO pathologic type (figure). PHMF/cancer cell index is useful for prognostic evaluation of pulmonary adenocarcinoma. PHMF/cancercell index, cancercell index, and lymphatic invasion are strongly correlated with prognosis. The number of cancer cells correlates with Noguchi’s classification and WHO pathologic types.