Journal Article
. 2014 Sep; 8(4):1482-1486.
doi: 10.3892/ol.2014.2366.

Quantitative histopathological assessment of ocular surface squamous neoplasia using digital image analysis

Rimvydas Ašoklis 1 Aistė Kadziauskienė 1 Rasa Paulavičienė 2 Donatas Petroška 3 Arvydas Laurinavičius 3 
Affiliations
  • PMID: 25202353
  •     22 References

Abstract

The aim of this retrospective pilot study was to evaluate the Aperio nuclear V9 algorithm as an image analysis tool to observe the histopathological changes of ocular surface squamous neoplasia (OSSN). A histopathological assessment, including the Ki-67 proliferative index (PI) of immunohistochemically-stained tumor conjunctiva (TC) and healthy conjunctiva (HC) tissues, was performed in six cases of OSSN. The Aperio V9 algorithm was applied to digital images of the tissue specimens to count the Ki-67 PI and to measure the nuclear area indices. This digital algorithm was validated using stereological and visual analysis methods. The visual scoring of Ki-67 PI ranged from 22 to 60% (mean, 38.5%), and from 5 to 20% (mean 9.5%) in TC and HC tissue, respectively. The computer-aided analysis, using the Aperio nuclear V9 algorithm, revealed that the Ki-67 PI ranged from 21.5 to 43.5% (mean, 33.6%), and from 1.9 to 21.0% (mean, 11.8%) in the TC and HC tissue, respectively. The stereological method demonstrated that the Ki-67 PI ranged from 30.1 to 51.5% (mean, 41.0%), and from 3.2 to 30.1% (mean, 15.1%) in the TC and HC tissues, respectively. The strongest association in the collinearity of regression analysis was observed between the Aperio nuclear V9 algorithm/stereological models in the TC tissue (r2=0.7; P=0.04) and the HC tissue (r2=0.7; P=0.03), and the visual/stereological models in the TC tissue (r2=0.7; P=0.04) and the visual/Aperio nuclear V9 algorithm models in the HC tissue (r2=0.7; P=0.04). A weak and statistically insignificant association was identified between the visual/Aperio nuclear V9 algorithm analysis in the TC tissue (r2=0.4; P=0.2) and the visual/stereological models in the HC tissue (r2=0.5; P=0.13). No significant difference was observed between the nuclear area of the TC (mean, 36.5 μm2) and HC (mean, 35.7 μm2; P=0.88) tissues. It was concluded that the Aperio nuclear V9 algorithm is a useful tool for the reliable analysis of histopathological changes of OSSN. The results of this computer-aided algorithm correlate strongly with the stereological method when assessing the Ki-67 PI.

Keywords: Ki-67; digital image analysis; ocular surface squamous neoplasia.

Intraepithelial and invasive squamous cell carcinoma of the conjunctiva: analysis of 60 cases.
M Tunc, D H Char, B Crawford, T Miller.
Br J Ophthalmol, 1999 Apr 21; 83(1). PMID: 10209445    Free PMC article.
Ki-67 labeling index as a marker of malignancy in ocular surface neoplasms.
Maki Ohara, Chie Sotozono, Yasunari Tsuchihashi, Shigeru Kinoshita.
Jpn J Ophthalmol, 2004 Dec 14; 48(6). PMID: 15592775
Squamous cell carcinoma of the conjunctiva: a series of 26 cases.
Penelope A McKelvie, Mark Daniell, +2 authors, John D Santamaria.
Br J Ophthalmol, 2002 Jan 30; 86(2). PMID: 11815342    Free PMC article.
Image analysis tools for evaluation of microscopic views of immunohistochemically stained specimen in medical research-a review.
Keerthana Prasad, Gopalakrishna K Prabhu.
J Med Syst, 2011 May 18; 36(4). PMID: 21584771
Review.
Retrospective analysis of 235 unselected patients with mantle cell lymphoma confirms prognostic relevance of Mantle Cell Lymphoma International Prognostic Index and Ki-67 in the era of rituximab: long-term data from the Czech Lymphoma Project Database.
David Salek, Pavla Vesela, +14 authors, Marek Trněný.
Leuk Lymphoma, 2013 Jun 19; 55(4). PMID: 23772666
Computer-assisted imaging algorithms facilitate histomorphometric quantification of kidney damage in rodent renal failure models.
Marcin Klapczynski, Gerard D Gagne, +5 authors, Eugene W Shek.
J Pathol Inform, 2012 May 23; 3. PMID: 22616032    Free PMC article.
Using image analysis as a tool for assessment of prognostic and predictive biomarkers for breast cancer: How reliable is it?
Mark C Lloyd, Pushpa Allam-Nandyala, +3 authors, Marilyn M Bui.
J Pathol Inform, 2011 Jan 12; 1. PMID: 21221174    Free PMC article.
A comparison between manual and automated evaluations of tissue microarray patterns of protein expression.
Arthur W Alvarenga, Claudia M Coutinho-Camillo, +5 authors, Glaucia N M Hajj.
J Histochem Cytochem, 2013 Jan 24; 61(4). PMID: 23340270    Free PMC article.
Digital pathology evaluation of complement C4d component deposition in the kidney allograft biopsies is a useful tool to improve reproducibility of the scoring.
Ernesta Brazdziute, Arvydas Laurinavicius.
Diagn Pathol, 2011 Apr 22; 6 Suppl 1. PMID: 21489200    Free PMC article.
Computer-derived nuclear features distinguish malignant from benign breast cytology.
W H Wolberg, W N Street, D M Heisey, O L Mangasarian.
Hum Pathol, 1995 Jul 01; 26(7). PMID: 7628853
Expression of cell cycle-regulatory proteins, MIB-1, p16, p53, and p63, in squamous cell carcinoma of conjunctiva: not associated with human papillomavirus infection.
Shih-Ming Jung, Hsin-Chiung Lin, +4 authors, Chyong-Huey Lai.
Virchows Arch, 2005 Dec 06; 448(3). PMID: 16328355
Proliferative activity in human breast cancer: Ki-67 automated evaluation and the influence of different Ki-67 equivalent antibodies.
S Fasanella, E Leonardi, +11 authors, M Barbareschi.
Diagn Pathol, 2011 Apr 22; 6 Suppl 1. PMID: 21489202    Free PMC article.
Squamous cell carcinoma of the conjunctiva.
J Yang, C S Foster.
Int Ophthalmol Clin, 1998 Jan 16; 37(4). PMID: 9429933
Review.
Immunohistochemistry profiles of breast ductal carcinoma: factor analysis of digital image analysis data.
Arvydas Laurinavicius, Aida Laurinaviciene, +3 authors, Juozas Lazutka.
Diagn Pathol, 2012 Mar 20; 7. PMID: 22424533    Free PMC article.
Ocular surface squamous neoplasia.
Christine A Kiire, Sathish Srinivasan, Carol L Karp.
Int Ophthalmol Clin, 2010 Jul 09; 50(3). PMID: 20611016
Review.
Introduction and first clinical application of a simplified immunohistochemical validation system confirms prognostic impact of KI-67 and CK20 for stage T1 urothelial bladder carcinoma: single-center analysis of eight biomarkers in a series of three hundred six patients.
Wolfgang Otto, Stefan Denzinger, +8 authors, Fabian Eder.
Clin Genitourin Cancer, 2013 Jul 16; 11(4). PMID: 23850551
The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins.
C Schlüter, M Duchrow, +4 authors, J Gerdes.
J Cell Biol, 1993 Nov 01; 123(3). PMID: 8227122    Free PMC article.
Highly Cited.
Review of imaging solutions for integrated quantitative immunohistochemistry in the Pathology daily practice.
Marcial García Rojo, Gloria Bueno, Janina Slodkowska.
Folia Histochem Cytobiol, 2010 Feb 19; 47(3). PMID: 20164017
Review.
Expression and histopathological correlation of CCR9 and CCL25 in ovarian cancer.
Rajesh Singh, Cecil R Stockard, +2 authors, Shailesh Singh.
Int J Oncol, 2011 Jun 04; 39(2). PMID: 21637913    Free PMC article.
Quantitative image analysis in the assessment of diffuse large B-cell lymphoma.
Devon S Chabot-Richards, David R Martin, +2 authors, Kristin E Hunt.
Mod Pathol, 2011 Aug 16; 24(12). PMID: 21841768    Free PMC article.
Study on breast carcinoma Her2/neu and hormonal receptors status assessed by automated images analysis systems: ACIS III (Dako) and ScanScope (Aperio).
Janina Słodkowska, Violetta Filas, +6 authors, Marcial Garcia Rojo.
Folia Histochem Cytobiol, 2010 Jun 10; 48(1). PMID: 20529811
The clinical significance of Ki-67 as a marker of prognostic value and chemosensitivity prediction in hormone-receptor-positive breast cancer: a meta-analysis of the published literature.
Yu Liu, Wenjin Yin, +3 authors, Jinsong Lu.
Curr Med Res Opin, 2013 Aug 10; 29(11). PMID: 23927551