Expression and significance of PHH3 in pancreatic neuroendocrine neoplasms

Abstract

Objective To investigate the expression of phospho-histone H3(PHH3) protein in pancreatic neuroendocrine neoplasms (PNENs) and explore its potential value for pathological grading of PNENs. Methods Clinical and pathological data of 283 patients with PNENs treated in Changhai Hospital from December 2000 to May 2016 were retrospectively analyzed. PNENs tissue chip was prepared, and immunohistochemistry was used to examine the expression of PHH3 and Ki67. The receiver operating characteristic curve for PHH3 was drawn and the area under the curve(AUC) was calculated to determine the cutoff value for PNENs grading. Ki67 was used for PNENs grading according to domestic and international criteria for PNENs classification. The relationship of PHH3 and Ki67 classification with clinical pathological features and prognosis of PNENs as well as the correlation between the two classification methods were analyzed. Results Of 283 patients, 132 were male and 151 were female, aged from 16 to 78 years old. The average age was (50±1) years old. There were 44 cases with functional PNENs and 239 with non-functional PNENs. The diameter of tumors ranged from 1.1 cm to 17 cm and the average diameter was (4.1±1.2)cm. According to the Ki67 standard, there were 127, 116, 33 and 7 cases of Grade G1, G2, pancreatic neuroendocrine tumor(PNET) G3 and pancreatic neuroendocrine cancer(PNEC) G3. According to the PHH3 standard, there were 118, 119, 38 and 8 cases of Grade G1, G2, PNET G3 and PNEC G3. There was a positive correlation between the two grading criteria (r=0.941, P 0.05), but were both positively correlated with tumor size, histological grade, lymph node metastasis, TNM stage and prognosis (all P<0.05). The average time of observing PHH3 and Ki67 staining per case in the immunohistochemistry of tissue chip was 9 min and 45 min, respectively. Conclusions Detection of PHH3 expression in PNENs can be used for the pathological diagnosis, grading and prognostic evaluation, which was more accurate and convenient than Ki67 criteria. Key words: Pancreatic neoplasms; Neuroendocrine tumors; Phospho-histone H3; Immunohistochemistry