PHH3 as an Ancillary Mitotic Marker in Gastrointestinal Stromal Tumors
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: Counting mitoses is subjective and time-consuming. The adjunctive diagnostic utility of a recently reported mitotic marker, phosphohistone H3 (PHH3), was investigated in gastrointestinal stromal tumors (GISTs). Methods: We reviewed 77 GISTs for several proliferative indices. These included the mitotic count per 50 high power fields (HPFs), the immunohistochemical Ki-67 labeling index and the immunohistochemical PHH3 mitotic index (MI). For comparison, Spearman’s rank correlation and interclass correlation coefficient were used. Results: Mitotic counts ranged from 0–138 (mean, 7.57±2.34) and the PHH3 MI ranged from 0–126 per 50 HPFs (mean, 9.61±2.27). We found a positive correlation between mitotic counts and PHH3 MI (r=0.810, p<.001). The inter-observer correlation coefficient for three participants was 0.975 for mitotic counts and 0.940 for the PHH3 MI. When using the PHH3 MI instead of mitotic counts in the Armed Forces Institute of Pathology (AFIP) stratification criteria, 10 cases were reclassified. In one patient with a mitotic count of 2 and a PHH3 MI of 6 per 50 HPFs, distant metastasis occurred. Conclusions: In GISTs, the PHH3 MI correlated adequately with mitotic counts and can be used as a useful adjunctive to count mitotic figures efficiently.
Abstract
Background: Counting mitoses is subjective and time-consuming. The adjunctive diagnostic utility of a recently reported mitotic marker, phosphohistone H3 (PHH3), was investigated in gastrointestinal stromal tumors (GISTs). Methods: We reviewed 77 GISTs for several proliferative indices. These included the mitotic count per 50 high power fields (HPFs), the immunohistochemical Ki-67 labeling index and the immunohistochemical PHH3 mitotic index (MI). For comparison, Spearman’s rank correlation and interclass correlation coefficient were used. Results: Mitotic counts ranged from 0–138 (mean, 7.57±2.34) and the PHH3 MI ranged from 0–126 per 50 HPFs (mean, 9.61±2.27). We found a positive correlation between mitotic counts and PHH3 MI (r=0.810, p<.001). The inter-observer correlation coefficient for three participants was 0.975 for mitotic counts and 0.940 for the PHH3 MI. When using the PHH3 MI instead of mitotic counts in the Armed Forces Institute of Pathology (AFIP) stratification criteria, 10 cases were reclassified. In one patient with a mitotic count of 2 and a PHH3 MI of 6 per 50 HPFs, distant metastasis occurred. Conclusions: In GISTs, the PHH3 MI correlated adequately with mitotic counts and can be used as a useful adjunctive to count mitotic figures efficiently.
참고문헌 (26)
- Miettinen M, "Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis", Arch Pathol Lab Med, 130, pp.1466~1478 (2006)
- Corless CL, "Biology of gastrointestinal stromal tumors", J Clin Oncol, 22, pp.3813~3825 (2004)
- Franquemont DW, "Differentiation and risk assessment of gastrointestinal stromal tumors", Am J Clin Pathol, 103, pp.41~47 (1995)
- Fletcher CD, "Diagnosis of gastrointestinal stromal tumors: a consensus approach", Hum Pathol, 33, pp.459~465 (2002)
- Miettinen M, "Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up", Am J Surg Pathol, 29, pp.52~68 (2005)
- Miettinen M, "Gastrointestinal stromal tumors of the jejunum and ileum: a clinicopathologic, immunohistochemical, and molecular genetic study of 906 cases before imatinib with long-term follow-up", Am J Surg Pathol, 30, pp.477~489 (2006)
- Tapia C, "Two mitosis-specific antibodies, MPM-2 and phospho-histone H3 (Ser28), allow rapid and precise determination of mitotic activity", Am J Surg Pathol, 30, pp.83~89 (2006)
- Agaimy A, "Gastrointestinal stromal tumors (GIST) from risk stratification systems to the new TNM proposal: more questions than answers? A review emphasizing the need for a standardized GIST reporting", Int J Clin Exp Pathol, 3, pp.461~471 (2010)
- Hendzel MJ, "Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation", Chromosoma, 106, pp.348~360 (1997)
- Ribalta T, "The mitosis-specific antibody anti-phosphohistone-H3(PHH3)facilitates rapid reliable grading of meningiomas according to WHO 2000 criteria", Am J Surg Pathol, 28, pp.1532~1536 (2004)
- Kim YJ, "Prognostic significance of the mitotic index using the mitosis marker anti-phosphohistone H3 in meningiomas", Am J Clin Pathol, 128, pp.118~125 (2007)
- Fukushima S, "Sensitivity and usefulness of anti-phosphohistone-H3 antibody immunostaining for counting mitotic figures in meningioma cases", Brain Tumor Pathol, 26, pp.51~57 (2009)
- Bossard C, "Phosphohistone H3 labelling for histoprognostic grading of breast adenocarcinomas and computer-assisted determination of mitotic index", J Clin Pathol, 59, pp.706~710 (2006)
- Nasr MR, "Comparison of pHH3, Ki-67, and survivin immunoreactivity in benign and malignant melanocytic lesions", Am J Dermatopathol, 30, pp.117~122 (2008)
- Veras E, "Mitosis-specific marker phospho-histone H3 in the assessment of mitotic index in uterine smooth muscle tumors: a pilot study", Int J Gynecol Pathol, 28, pp.316~321 (2009)
- Tsuta K, "Using the mitosis-specific marker anti-phosphohistone H3 to assess mitosis in pulmonary neuroendocrine carcinomas", Am J Clin Pathol, 136, pp.252~259 (2011)
- Takahashi H, "Overexpression of phosphorylated histone H3 is an indicator of poor prognosis in gastric adenocarcinoma patients", Appl Immunohistochem Mol Morphol, 14, pp.296~302 (2006)
- Nakashima S, "Anti-phosphohistone H3 as an independent prognostic factor in human esophageal squamous cell carcinoma", Anticancer Res, 33, pp.461~467 (2013)
- Kim A, "Usefulness of anti‐phosphohistone H3 immunoreactivity to determine mitotic rate in gastrointestinal stromal tumors", Basic Appl Pathol, 5, pp.91~97 (2012)
- Carrillo R, "Prognostic significance of DNA ploidy and proliferative index(MIB-1 index)in gastrointestinal stromal tumors", Hum Pathol, 28, pp.160~165 (1997)
- Toquet C, "Elevated (> or = 10%) MIB-1 proliferative index correlates with poor outcome in gastric stromal tumor patients: a study of 35 cases", Dig Dis Sci, 47, pp.2247~2253 (2002)
- Filiz G, "The relationship between MIB-1 proliferative activity and mitotic index in gastrointestinal stromal tumors", Hepatogastroenterology, 54, pp.438~441 (2007)
- Gerdes J, "Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67", J Immunol, 133, pp.1710~1715 (1984)
- Juan G, "Histone H3 phosphorylation and expression of cyclins A and B1 measured in individual cells during their progression through G2 and mitosis", Cytometry, 32, pp.71~77 (1998)
- Brenner RM, "Immunocytochemical assessment of mitotic activity with an antibody to phosphorylated histone H3 in the macaque and human endometrium", Hum Reprod, 18, pp.1185~1193 (2003)
- Schimming TT, "pHH3 immunostaining improves interobserver agreement of mitotic index in thin melanomas", Am J Dermatopathol, 34, pp.266~269 (2012)