title: Mitotic Index Determined by Phosphohistone H3 Immunohistochemistry for Precise Grading in Follicular Lymphoma.
abstract: The World Health Organization classification recommends follicular lymphoma (FL) grading (G1-3) by considering centroblast number, while also suggesting its influence on disease outcome. As centroblast counting and other proliferation markers have limitations, we looked for more specific measures of cellular activity in FL. Phosphorylated histone H3 (pHH3) was widely applied for the objective detection of mitotic activity in different tumors. The aim was to evaluate the utility of pHH3 protein in FL grading and compare its value with the classical features of cell proliferation. Representative samples from 48 FL patients and 9 samples with follicular hyperplasia were examined. Hematoxylin-eosin-based mitosis index (HE-MI), number of mitotic figures based on anti-pHH3 immunohistochemical staining (pHH3-MI), and percentage of Ki-67-positive cells [proliferation index (PI)] were determined and compared with centroblast-based histologic grade. PHH3-MI showed significant correlation with HE-MI (r=0.85, P<0.0001) and PI (r=0.84, P<0.0001). All 3 cell proliferation parameters showed significant correlation with histologic grade: HE-MI versus grade, r=0.85 (P<0.0001); PI versus grade, r=0.74 (P<0.0001); pHH3-MI versus grade, r=0.80 (P<0.0001). PHH3-MI showed continuous increase with the histologic grade. The pHH3-MI value was distinctive between the G2 and the G1 FL groups (P<0.0001) and was increased in G3 FL compared with that in the G2 FL group (P=0.0020). In conclusion, easy-to-perform mitotic counting following phosphohistone H3 immunohistochemistry (pHH3-MI) correlates well with centroblast-based grading. PHH3 immunohistochemistry offers a reliable quantification tool supporting lymphoma grading and can be recommended as an additional parameter for the precise subcategorization of FL cases.
authors.affiliation: Departments of Pathology.
authors.forename: Judit
authors.initials: J
authors.lastname: Bedekovics
authors.affiliation: Departments of Pathology.
authors.forename: Gábor
authors.initials: G
authors.lastname: Irsai
authors.affiliation: Departments of Pathology.
authors.forename: Katalin
authors.initials: K
authors.lastname: Hegyi
authors.affiliation: Departments of Pathology.
authors.forename: Lívia
authors.initials: L
authors.lastname: Beke
authors.affiliation: Laboratory of Tumor Pathology and Molecular Diagnostics, Szeged, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Krenács
authors.affiliation: Hematology, University of Debrecen, Debrecen.
authors.forename: Lajos
authors.initials: L
authors.lastname: Gergely
authors.affiliation: Departments of Pathology.
authors.forename: Gábor
authors.initials: G
authors.lastname: Méhes
mesh_terms: D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D005260:Female; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008224:Lymphoma, Follicular / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation
chemical_list: D006657:Histones; D009363:Neoplasm Proteins