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Immunostaining for p16(INK4a) used as a conjunctive tool improves interobserver agreement of the histologic diagnosis of cervical intraepithelial neoplasia

Horn, Lars-Christian; Reichert, Anja; Oster, Anne; Frost Arndal, Sanne; Trunk, Marcus J.; Ridder, Ruediger; Rassmussen, Ole Feldballe; Jelkenkrantz, Kaj LU ; Christiansen, Pernille and Eck, Matthias, et al. (2008) In American Journal of Surgical Pathology 32(4). p.502-512
Abstract
The quality of cervical histopathology is critical to cervical cancer prevention, cancer treatment, and research programs. On the basis of the histology results further patient management is determined. However, the diagnostic interpretation of histologic hematoxylin-eosin (H&E)-stained slides is affected by substantial rates of discordance among pathologists. Overexpression of the cyclin-dependent kinase inhibitor p16(INK4a), a cell cycle regulating protein, has been shown to be strongly correlated with dysplastic lesions of the cervix uteri. In this study.. we assessed whether p16(INK4a) immunohistochemistry may increase the performance of pathologists in diagnosing squamous lesions in cervical punch and cone biopsies. When using a... (More)
The quality of cervical histopathology is critical to cervical cancer prevention, cancer treatment, and research programs. On the basis of the histology results further patient management is determined. However, the diagnostic interpretation of histologic hematoxylin-eosin (H&E)-stained slides is affected by substantial rates of discordance among pathologists. Overexpression of the cyclin-dependent kinase inhibitor p16(INK4a), a cell cycle regulating protein, has been shown to be strongly correlated with dysplastic lesions of the cervix uteri. In this study.. we assessed whether p16(INK4a) immunohistochemistry may increase the performance of pathologists in diagnosing squamous lesions in cervical punch and cone biopsies. When using a consecutive p 16(INK4a)-stained slide in conjunction to the H&E-stained slide, interobserver agreement between 6 pathologists improved significantly for both cervical punch and cone biopsies (P < 0.001). For punch biopsies (n = 247), K value increased from 0.49 (moderate agreement) to 0.64 indicating substantial agreement, and interobserver agreement for cone biopsies (n = 249) improved from 0.63 (conventional H&E slide reading) to 0.70 when H&E-stained slides were read conjunctively with p16(INK4a)-stained slides. In comparison to a common consensus diagnosis established by 3 independent experts, 4 pathologists reached an improvement with the conjunctive p16(INK4a) test, 2 of them showing significantly better agreement (P < 0.001 and P = 0.002, respectively). P-16INK4a immunohistochemistry as an adjunct to conventional H&E-stained specimens thus contributes to a more reproducible diagnosis of cervical intraepithelial neoplasia, and may be a valuable aid for the interpretation of cervical histology. (Less)
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published
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keywords
diagnostic performance, quality control, cervical neoplasms, CIN, p16(INK4a), interobserver agreement, immunohistochemistry
in
American Journal of Surgical Pathology
volume
32
issue
4
pages
502 - 512
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000254562800002
ISSN
1532-0979
language
English
LU publication?
yes
id
da5b8d6c-25d6-4556-b0ae-492a78fd1a3c (old id 1182748)
date added to LUP
2009-07-09 10:27:55
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2016-04-15 19:28:39
@article{da5b8d6c-25d6-4556-b0ae-492a78fd1a3c,
  abstract     = {The quality of cervical histopathology is critical to cervical cancer prevention, cancer treatment, and research programs. On the basis of the histology results further patient management is determined. However, the diagnostic interpretation of histologic hematoxylin-eosin (H&amp;E)-stained slides is affected by substantial rates of discordance among pathologists. Overexpression of the cyclin-dependent kinase inhibitor p16(INK4a), a cell cycle regulating protein, has been shown to be strongly correlated with dysplastic lesions of the cervix uteri. In this study.. we assessed whether p16(INK4a) immunohistochemistry may increase the performance of pathologists in diagnosing squamous lesions in cervical punch and cone biopsies. When using a consecutive p 16(INK4a)-stained slide in conjunction to the H&amp;E-stained slide, interobserver agreement between 6 pathologists improved significantly for both cervical punch and cone biopsies (P &lt; 0.001). For punch biopsies (n = 247), K value increased from 0.49 (moderate agreement) to 0.64 indicating substantial agreement, and interobserver agreement for cone biopsies (n = 249) improved from 0.63 (conventional H&amp;E slide reading) to 0.70 when H&amp;E-stained slides were read conjunctively with p16(INK4a)-stained slides. In comparison to a common consensus diagnosis established by 3 independent experts, 4 pathologists reached an improvement with the conjunctive p16(INK4a) test, 2 of them showing significantly better agreement (P &lt; 0.001 and P = 0.002, respectively). P-16INK4a immunohistochemistry as an adjunct to conventional H&amp;E-stained specimens thus contributes to a more reproducible diagnosis of cervical intraepithelial neoplasia, and may be a valuable aid for the interpretation of cervical histology.},
  author       = {Horn, Lars-Christian and Reichert, Anja and Oster, Anne and Frost Arndal, Sanne and Trunk, Marcus J. and Ridder, Ruediger and Rassmussen, Ole Feldballe and Jelkenkrantz, Kaj and Christiansen, Pernille and Eck, Matthias and Lorey, Thomas and Skovlund, Vibeke Ravn and Ruediger, Thomas and Schneider, Volker and Schmidt, Dietmar},
  issn         = {1532-0979},
  keyword      = {diagnostic performance,quality control,cervical neoplasms,CIN,p16(INK4a),interobserver agreement,immunohistochemistry},
  language     = {eng},
  number       = {4},
  pages        = {502--512},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {American Journal of Surgical Pathology},
  title        = {Immunostaining for p16(INK4a) used as a conjunctive tool improves interobserver agreement of the histologic diagnosis of cervical intraepithelial neoplasia},
  volume       = {32},
  year         = {2008},
}