title: Mitotic rate in melanoma: prognostic value of immunostaining and computer-assisted image analysis.
abstract: The prognostic value of mitotic rate in melanoma is increasingly recognized, particularly in thin melanoma in which the presence or absence of a single mitosis/mm can change staging from T1a to T1b. Still, accurate mitotic rate calculation (mitoses/mm) on hematoxylin and eosin (H&E)-stained sections can be challenging. Antimonoclonal mitotic protein-2 (MPM-2) and antiphosphohistone-H3 (PHH3) are 2 antibodies reported to be more mitosis-specific than other markers of proliferation such as Ki-67. We used light microscopy and computer-assisted image analysis software to quantify MPM-2 and PHH3 staining in melanoma. We then compared mitotic rates by each method with conventional H&E-based mitotic rate for correlation with clinical outcomes. Our study included primary tissues from 190 nonconsecutive cutaneous melanoma patients who were prospectively enrolled at New York University Langone Medical Center with information on age, gender, and primary tumor characteristics. The mitotic rate was quantified manually by light microscopy of corresponding H&E-stained, MPM-2-stained, and PHH3-stained sections. Computer-assisted image analysis was then used to quantify immunolabeled mitoses on the previously examined PHH3 and MPM-2 slides. We then analyzed the association between mitotic rate and both progression-free and melanoma-specific survival. Univariate analysis of PHH3 found significant correlation between increased PHH3 mitotic rate and decreased progression-free survival (P=0.04). Computer-assisted image analysis enhanced the correlation of PHH3 mitotic rate with progression-free survival (P=0.02). Regardless of the detection method, neither MPM-2 nor PHH3 offered significant advantage over conventional H&E determination of mitotic rate.
authors: Department of Pathology, New York University Cancer Institute, New York University School of Medicine, New York, NY 10016, USA.
authors: Christopher S
authors: CS
authors: Hale
authors: Meng
authors: M
authors: Qian
authors: Michelle W
authors: MW
authors: Ma
authors: Patrick
authors: P
authors: Scanlon
authors: Russell S
authors: RS
authors: Berman
authors: Richard L
authors: RL
authors: Shapiro
authors: Anna C
authors: AC
authors: Pavlick
authors: Yongzhao
authors: Y
authors: Shao
authors: David
authors: D
authors: Polsky
authors: Iman
authors: I
authors: Osman
authors: Farbod
authors: F
authors: Darvishian
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D008940:Mitotic Index / Q000379:methods*; D009367:Neoplasm Staging / Q000379:methods*; D016016:Proportional Hazards Models; D012878:Skin Neoplasms / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor
references: Acta Ophthalmol. 2011 Mar;89(2):e155-60
references: 19900200
references: Anal Cell Pathol (Amst). 2012;35(2):97-100
references: 21965283
references: J Invest Dermatol. 1995 Jul;105(1):22-6
references: 7615970
references: Biochem J. 2007 Apr 15;403(2):235-42
references: 17212588
references: Ann Surg Oncol. 2004 Apr;11(4):426-33
references: 15070604
references: J Clin Oncol. 2005 Sep 1;23(25):5993-6001
references: 16135467
references: Am J Surg Pathol. 2006 Jan;30(1):83-9
references: 16330946
references: Cancer. 2003 Mar 15;97(6):1488-98
references: 12627514
references: J Clin Oncol. 2005 Nov 1;23(31):8048-56
references: 16258103
references: J Natl Cancer Inst. 1989 Dec 20;81(24):1893-904
references: 2593166
references: J Invest Dermatol. 2012 Apr;132(4):1247-52
references: 22297638
references: J Biol Chem. 1999 Sep 3;274(36):25543-9
references: 10464286
references: Ann Oncol. 2007 Jun;18 Suppl 6:vi136-40
references: 17591808
references: J Clin Pathol. 2006 Jul;59(7):706-10
references: 16461563
references: Am J Surg. 2010 Dec;200(6):759-63; discussion 763-4
references: 21146017
references: Am J Dermatopathol. 1998 Aug;20(4):357-61
references: 9700373
references: J Am Acad Dermatol. 1987 Feb;16(2 Pt 1):361-7
references: 3819073
references: J Clin Oncol. 2011 Jun 1;29(16):2199-205
references: 21519009
references: Melanoma Res. 2012 Feb;22(1):1-8
references: 22108608
references: Histopathology. 2001 Jul;39(1):1-8
references: 11454038
references: BMC Cancer. 2010 Apr 14;10:140
references: 20398247
references: J Cutan Pathol. 2012 Mar;39(3):324-30
references: 22335591
references: Cancer. 2002 Aug 1;95(3):634-40
references: 12209757
references: Am J Dermatopathol. 2010 Oct;32(7):650-4
references: 20559123
references: J Clin Oncol. 2011 Mar 1;29(7):852-8
references: 21189388
references: Am J Dermatopathol. 2010 Oct;32(7):643-9
references: 20661119
references: Arch Pathol Lab Med. 2000 Feb;124(2):221-7
references: 10656730
references: Am J Clin Pathol. 2007 Mar;127(3):380-4
references: 17276944
references: Am J Transl Res. 2009;1(1):35-43
references: 19966936
references: MLO Med Lab Obs. 2009 Mar;41(3):31
references: 19374184
references: Am J Dermatopathol. 2012 May;34(3):266-9
references: 22197861
references: J Biol Chem. 2000 Nov 3;275(44):34710-8
references: 10942766
references: J Clin Oncol. 2009 Dec 20;27(36):6199-206
references: 19917835
references: Proc Natl Acad Sci U S A. 1983 May;80(10):2926-30
references: 6574461
references: Am J Dermatopathol. 2008 Apr;30(2):117-22
references: 18360113
references: J Cutan Pathol. 2005 Apr;32(4):268-73
references: 15769275