Objective: According to the World Health Organization, pancreatic endocrine tumors are graded by assessment of the Ki67 proliferation index and/or mitotic count. The objective was to find comparable grading on the basis of the novel mitotic marker phosphohistone-H3 (PHH3). Study Design: A computer-assisted system was used to assess 23 cell blocks stained with PHH3 and Ki67 antibodies. We investigated possible cut-points for PHH3 and computed percent agreement between the PHH3- and Ki67-based grading. Results: The Spearman correlation between percent Ki67 positive and percent PHH3 positive was 0.76 (p = 0.001). A value of 0.3% for the lower cut-point (‘cut-point 1', differentiating between grades 1 and 2) and values of about 1.8-1.9% for the higher cut-point (‘cut-point 2', differentiating between grades 2 and 3) shows optimal agreement between PHH3 and Ki67 grading. The percentage of positive cells was much higher for Ki67 than for PHH3 (mean 10.6 vs. 3.0%). Conclusions: PHH3 has good correlation with Ki67, but the range of PHH3 positivity is much narrower than that of Ki67 (range 0-4% for PHH3 vs. 0-50% for Ki67). Therefore, to be as accurate, grading on the basis of PHH3 requires evaluation of a larger number of tumor cells for a precise determination of percent PHH3-positive nuclei.

Bosman FT, Carneiro F, Hruban RH, Theise ND (eds): WHO Classification of Tumours of the Digestive System, ed 4. Geneva, WHO, 2010.
Piani C, Franchi GM, Cappelletti C, Scavini M, Albarello L, Zerbi A, Giorgio Arcidiacono P, Bosi E, Manzoni MF: Cytological Ki-67 in pancreatic endocrine tumours: an opportunity for pre-operative grading. Endocr Relat Cancer 2008;15:175-181.
Jamali M, Chetty R: Predicting prognosis in gastroentero-pancreatic neuroendocrine tumors: an overview and the value of Ki-67 immunostaining. Endocr Pathol 2008;19:282-288.
Klimstra DS, Modlin IR, Adsay NV, Chetty R, Deshpande V, Gönen M, Jensen RT, Kidd M, Kulke MH, Lloyd RV, Moran C, Moss SF, Oberg K, O'Toole D, Rindi G, Robert ME, Suster S, Tang LH, Tzen CY, Washington MK, Wiedenmann B, Yao J: Pathology reporting of neuroendocrine tumors: application of the Delphic consensus process to the development of a minimum pathology data set. Am J Surg Pathol 2010;34:300-313.
Chatzipantelis P, Konstantinou P, Kaklamanos M, Apostolou G, Salla C: The role of cytomorphology and proliferative activity in predicting biologic behavior of pancreatic neuroendocrine tumors: a study by endoscopic ultrasound-guided fine-needle aspiration cytology. Cancer 2009;117:211-216.
Alexiev BA, Darwin PE, Goloubeva O, Ioffe OB: Proliferative rate in endoscopic ultrasound fine-needle aspiration of pancreatic endocrine tumors: correlation with clinical behavior. Cancer 2009;117:40-45.
Kim YJ, Ketter R, Steudel WI, Feiden W: Prognostic significance of the mitotic index using the mitosis marker anti-phosphohistone H3 in meningiomas. Am J Clin Pathol 2007;128:118-125.
Ong CW, Kim LG, Kong HH, Low LY, Wang TT, Supriya S, Kathiresan M, Soong R, Salto-Tellez M: Computer-assisted pathological immunohistochemistry scoring is more time-effective than conventional scoring, but provides no analytical advantage. Histopathology 2010;56:523-529.
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