title: Robust linear regression model of Ki-67 for mitotic rate in gastrointestinal stromal tumors.
abstract: Risk stratification of gastrointestinal stromal tumors (GISTs) by tumor size, lymph node and metastasis status is crucially affected by mitotic activity. To date, no studies have quantitatively compared mitotic activity in hematoxylin and eosin (H&E)-stained tissue sections with immunohistochemical markers, such as phosphohistone H3 (PHH3) and Ki-67. According to the TNM guidelines, the mitotic count on H&E sections and immunohistochemical PHH3-stained slides has been assessed per 50 high-power fields of 154 specimens of clinically documented GIST cases. The Ki-67-associated proliferation rate was evaluated on three digitalized hot spots using image analysis. The H&E-based mitotic rate was found to correlate significantly better with Ki-67-assessed proliferation activity than with PHH3-assessed proliferation activity (r=0.780; P<0.01). A linear regression model (analysis of variance; P<0.001) allowed reliable predictions of the H&E-associated mitoses based on the Ki-67 expression alone. Additionally, the Ki-67-associated proliferation revealed a higher and significant impact on the recurrence and metastasis rate of the GIST cases than by the classical H&E-based mitotic rate. The results of the present study indicated that the mitotic rate may be reliably and time-efficiently estimated by immunohistochemistry of Ki-67 using only three hot spots.
authors: Institute of Pathology, Paracelsus Medical University/Salzburger Landeskliniken, Salzburg A-5020, Austria.
authors: Ralf
authors: R
authors: Kemmerling
authors: Institute of Pathology, Paracelsus Medical University/Salzburger Landeskliniken, Salzburg A-5020, Austria ; University of Applied Sciences Upper Austria, Bio- and Environmental Engineering, Wels A-4600, Austria.
authors: Denis
authors: D
authors: Weyland
authors: Department of Internal Medicine I, Paracelsus Medical University/Salzburger Landeskliniken, Salzburg A-5020, Austria ; Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg A-5020, Austria.
authors: Tobias
authors: T
authors: Kiesslich
authors: Institute of Pathology, Paracelsus Medical University/Salzburger Landeskliniken, Salzburg A-5020, Austria.
authors: Romana
authors: R
authors: Illig
authors: Institute of Pathology, Paracelsus Medical University/Salzburger Landeskliniken, Salzburg A-5020, Austria.
authors: Eckhard
authors: E
authors: Klieser
authors: Department of Surgery, Paracelsus Medical University/Salzburger Landeskliniken, Salzburg A-5020, Austria.
authors: Tarkan
authors: T
authors: Jäger
authors: Institute of Pathology, Paracelsus Medical University/Salzburger Landeskliniken, Salzburg A-5020, Austria.
authors: Otto
authors: O
authors: Dietze
authors: Institute of Pathology, Paracelsus Medical University/Salzburger Landeskliniken, Salzburg A-5020, Austria.
authors: Daniel
authors: D
authors: Neureiter
keywords: Ki-67; PHH3; gastrointestinal stromal tumors; mitosis; proliferation