Immunhistochemistry by Means of Widely Agreed-Upon Markers (Cytokeratins 5/6 and 7, p63, Thyroid Transcription Factor-1, and Vimentin) on Small Biopsies.

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Immunhistochemistry by Means of Widely Agreed-Upon Markers (Cytokeratins 5/6 and 7, p63, Thyroid Transcription Factor-1, and Vimentin) on Small Biopsies of Non-small Cell Lung Cancer Effectively Parallels the Corresponding Profiling and Eventual Diagnoses on Surgical Specimens  Giuseppe Pelosi, MD, MIAC, Giulio Rossi, MD, Fabrizio Bianchi, DSc, PhD, Patrick Maisonneuve, Eng, Domenico Galetta, MD, Angelica Sonzogni, MD, Giulia Veronesi, MD, Lorenzo Spaggiari, MD, Mauro Papotti, MD, Mattia Barbareschi, MD, Paolo Graziano, MD, Andrea Decensi, MD, Alberto Cavazza, MD, Giuseppe Viale, MD, FRCPath  Journal of Thoracic Oncology  Volume 6, Issue 6, Pages 1039-1049 (June 2011) DOI: 10.1097/JTO.0b013e318211dd16 Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 Hierarchic unsupervised (A, C) and supervised (B, D) clustering analysis on both surgical specimens (SS in diagrams A and B) and biopsies (BS in diagrams C and D) across the entire tumor series under evaluation. A nonrandom distribution of the relevant markers was shown in both SS (A) and BS (C). Tumor clustering for conventional histology defined consistent profiles to occur for the main tumor types in both SS (B) and BS (D). In particular, CK7 and thyroid transcription factor-1 [TTF1] highlighted adenocarcinoma (AC), CK5/6 and p63 squamous cell carcinoma (SCC), and vimentin sarcomatoid carcinoma (SC) (other included two cases of adenosquamous carcinoma and a case of yolk sac tumor). Journal of Thoracic Oncology 2011 6, 1039-1049DOI: (10.1097/JTO.0b013e318211dd16) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Two-dimensional diagrams reporting the pairwise comparison for each marker between any two samples according to unsupervised (A) and supervised (B) hierarchical clustering analyses. High coefficients of correlation (C) were found for each marker between surgical specimens (marked as SS) and biopsies (marked as BS) (AC: adenocarcinoma; SCC: squamous cell carcinoma; SC: sarcomatoid carcinoma; other: two adenosquamous carcinomas and one yolk sac tumor). Journal of Thoracic Oncology 2011 6, 1039-1049DOI: (10.1097/JTO.0b013e318211dd16) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 Mosaic plot diagrams (the more surface of varying colored rectangles, the more amount of cases in the different tumor subsets) confirmed a close and distinct relationship of the clusters with the diverse tumor categories in surgical specimens (A) and biopsies (B). AC, adenocarcinoma; SCC, squamous cell carcinoma; SC, sarcomatoid carcinoma (the two cases of adenosquamous carcinoma and the case of yolk sac tumor were excluded from this analysis). Journal of Thoracic Oncology 2011 6, 1039-1049DOI: (10.1097/JTO.0b013e318211dd16) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 4 Area under the curve (AUC)-receiver operating characteristic (ROC) analysis curves for the different markers are shown in both surgical specimens (A) and small biopsies (B). The high values of the AUC in both types of material testified the high performance of IHC to correctly classify squamous cell carcinoma (p63+ and CK5/6+), adenocarcinoma (CK7+ and thyroid transcription factor-1 [TTF1]+), and sarcomatoid carcinoma (vimentin+). The two cases of adenosquamous carcinoma and the case of yolk sac tumor were excluded from the analysis for the sake of simplicity. Journal of Thoracic Oncology 2011 6, 1039-1049DOI: (10.1097/JTO.0b013e318211dd16) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 5 Simple rules one should follow for the correct subclassification of NSCLC in biopsy samples when using a five-hit, NSCLC-oriented antibody panel approach with thyroid transcription factor-1 (TTF1), CK7, CK5/6, p63, and vimentin. Journal of Thoracic Oncology 2011 6, 1039-1049DOI: (10.1097/JTO.0b013e318211dd16) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions