Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens Journal Article

  

Authors:	Rekhtman, N.; Ang, D. C.; Sima, C. S.; Travis, W. D.; Moreira, A. L.
Article Title:	Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens
Abstract:	Immunohistochemistry is increasingly utilized to differentiate lung adenocarcinoma and squamous cell carcinoma. However, detailed analysis of coexpression profiles of commonly used markers in large series of whole-tissue sections is lacking. Furthermore, the optimal diagnostic algorithm, particularly the minimal-marker combination, is not firmly established. We therefore studied whole-tissue sections of resected adenocarcinoma and squamous cell carcinoma (n315) with markers commonly used to identify adenocarcinoma (TTF-1) and squamous cell carcinoma (p63, CK5/6, 34ΒE12), and prospectively validated the devised algorithm in morphologically unclassifiable small biopsy/cytology specimens (n38). Analysis of whole-tissue sections showed that squamous cell carcinoma had a highly consistent immunoprofile (TTF-1-negative and p63/CK5/6/34ΒE12-diffuse) with only rare variation. In contrast, adenocarcinoma showed significant immunoheterogenetity for all squamous markers (p63 (32%), CK5/6 (18%), 34ΒE12 (82%)) and TTF-1 (89%). As a single marker, only diffuse TTF-1 was specific for adenocarcinoma whereas none of the squamous markers, even if diffuse, were entirely specific for squamous cell carcinoma. In contrast, coexpression profiles of TTF-1/p63 had only minimal overlap between adenocarcinoma and squamous cell carcinoma, and there was no overlap if CK5/6 was added as a third marker. An algorithm was devised in which TTF-1/p63 were used as the first-line panel, and CK5/6 was added for rare indeterminate cases. Prospective validation of this algorithm in small specimens showed 100% accuracy of adenocarcinoma vs squamous cell carcinoma prediction as determined by subsequent resection. In conclusion, although reactivity for squamous markers is common in lung adenocarcinoma, a two-marker panel of TTF-1/p63 is sufficient for subtyping of the majority of tumors as adenocarcinomas vs squamous cell carcinoma, and addition of CK5/6 is needed in only a small subset of cases. This simple algorithm achieves excellent accuracy in small specimens while conserving the tissue for potential predictive marker testing, which is now an essential consideration in advanced lung cancer specimens. © 2011 USCAP, Inc. All rights reserved.
Keywords:	immunohistochemistry; adult; human tissue; protein expression; aged; aged, 80 and over; middle aged; unclassified drug; major clinical study; dna-binding proteins; review; squamous cell carcinoma; carcinoma, squamous cell; disease marker; prospective study; sensitivity and specificity; prospective studies; adenocarcinoma; reproducibility of results; cytology; diagnosis, differential; lung neoplasms; tumor differentiation; tumor markers, biological; immunoreactivity; algorithms; biopsy; transcription factors; lung adenocarcinoma; ttf-1; algorithm; tumor suppressor proteins; predictive value of tests; protein p63; lung squamous cell carcinoma; cytokeratin 5; cytokeratin 6; keratins; lung biopsy; p63; thyroid transcription factor 1; keratin; 34be12; ck5/6; cytokeratin 34beta e12; keratin-5; keratin-6
Journal Title:	Modern Pathology
Volume:	24
Issue:	10
ISSN:	0893-3952
Publisher:	Nature Research
Date Published:	2011-10-01
Start Page:	1348
End Page:	1359
Language:	English
DOI:	10.1038/modpathol.2011.92
PROVIDER:	scopus
PUBMED:	21623384
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-80053570615&partnerID=40&md5=2d6d744c53eb5478c0437ea4d91b9884
Notes:	--- - "Export Date: 2 November 2011" - "CODEN: MODPE" - "Source: Scopus"

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