Abstract

IntroductionWhile some targeted agents should not be used in squamous cell carcinomas (SCCs), other agents might preferably target SCCs. In a previous microarray study, one of the top differentially expressed genes between adenocarcinomas (ACs) and SCCs is P63. It is a well-known marker of squamous differentiation, but surprisingly, its expression is not widely used for this purpose. Our goals in this study were (1) to further confirm our microarray data, (2) to analize the value of P63 immunohistochemistry (IHC) in reducing the number of large cell carcinoma (LCC) diagnoses in surgical specimens, and (3) to investigate the potential of P63 IHC to minimize the proportion of “carcinoma NOS (not otherwise specified)” in a prospective series of small tumor samples.MethodsWith these goals in mind, we studied (1) a tissue-microarray comprising 33 ACs and 99 SCCs on which we performed P63 IHC, (2) a series of 20 surgically resected LCCs studied for P63 and TTF-1 IHC, and (3) a prospective cohort of 66 small thoracic samples, including 32 carcinoma NOS, that were further classified by the result of P63 and TTF-1 IHC.ResultsThe results in the three independent cohorts were as follows: (1) P63 IHC was differentially expressed in SCCs when compared to ACs (p<0.0001); (2) half of the 20 (50%) LCCs were positive for P63 and were reclassified as SCCs; and (3) all P63 positive cases (34%) were diagnosed as SCCs.ConclusionsP63 IHC is useful for the identification of lung SCCs.

Highlights

  • While some targeted agents should not be used in squamous cell carcinomas (SCCs), other agents might preferably target SCCs

  • With these goals in mind, we studied (1) a tissue-microarray comprising 33 ACs and 99 SCCs on which we performed P63 IHC, (2) a series of 20 surgically resected large cell carcinoma (LCC) studied for P63 and TTF-1 IHC, and (3) a prospective cohort of 66 small thoracic samples, including 32 carcinoma not otherwise specified (NOS), that were further classified by the result of P63 and TTF-1 IHC

  • The results in the three independent cohorts were as follows: (1) P63 IHC was differentially expressed in SCCs when compared to ACs (p,0.0001); (2) half of the 20 (50%) LCCs were positive for P63 and were reclassified as SCCs; and (3) all P63 positive cases (34%) were diagnosed as SCCs

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Summary

Introduction

While some targeted agents should not be used in squamous cell carcinomas (SCCs), other agents might preferably target SCCs. In a previous microarray study, one of the top differentially expressed genes between adenocarcinomas (ACs) and SCCs is P63 It is a well-known marker of squamous differentiation, but surprisingly, its expression is not widely used for this purpose. In a previous microarray study, we compared primary lung adenocarcinoma (AC) with squamous cell carcinoma (SCC) in order to find new immunohistochemical antibodies that could improve the accuracy of the distinction in daily practice [3]. One of the top differentially expressed genes that we found was P63, a well-known marker of squamous differentiation but, surprisingly, its expression is not widely used for this purpose in pathology laboratories worldwide This result was validated with a tissue microarray (TMA) (Fig. 1 and Table 1)

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