The Use of P63 Immunohistochemistry for the Identification of Squamous Cell Carcinoma of the Lung

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.

The value of cytokeratin 5/6, p63 and thyroid transcription factor-1 in adenocarcinoma, squamous cell carcinoma and non-small-cell lung cancer of the lung

“…However, p63 specificity is not high because p63 can be stained focal and/or weak in some ACs (12,13,16). In our study, p63 positivity was observed in 4 AC cases which had TTF-1(+)/ CK5/6 (-).…”

“…Morphological misdiagnosis is more common in biopsy because of more limited tissue than in surgical specimens (5). For accurate diagnosis, immunohistochemistry is usually employed in both surgical and biopsy (10,12,13). The immunohistochemical use of CK5/6, TTF-1 and p63…”

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

“…7 Several recent studies showed that immunostains (and previously electron microscopy 42 ) can reveal the line of differentiation as adenocarcinoma vs squamous cell carcinoma in the majority of large cell carcinomas. 26,36,43,44 The proposed TTF-1/p63 algorithm could be used to determine biological identity within the large cell carcinoma, but this needs further study.…”

“…Given the recent insights into the clinical and biological significance of non-small cell carcinoma subtypes, several recent studies have analyzed the utility of various combinations of markers for the distinction of adenocarcinoma and squamous cell carcinoma. These studies were performed in small biopsies, [14][15][16] cytology, 17,23 and tissue microarrays, [24][25][26] and the proposed algorithms include between fourand six-marker panels. Although most studies agree on the inclusion of TTF-1 and p63 in the panel, there is no agreement on the role of additional markers.…”

Pulmonary Large Cell Carcinoma Lacking Squamous Differentiation Is Clinicopathologically Indistinguishable From Solid-Subtype Adenocarcinoma

“…As a result, LCC contains a heterogeneous mix of entities, which complicates any potential characterization studies or clinical trials. In addition to gene expression-based approaches, [11][12][13][14][15][16][17] multiple studies [18][19][20][21][22][23][24][25][26][27] have shown that LCC can be reclassified as ADC, SQC, or large cell neuroendocrine carcinoma by immunohistochemistry. The widespread use of immunohistochemistry in diagnostic practice may explain the decreasing incidence of LCC.…”