p40 (ΔNp63) and keratin 34βE12 provide greater diagnostic accuracy than p63 in the evaluation of small cell lung carcinoma in small biopsy samples.

The use of p63 has been advocated for separating small cell lung carcinoma from poorly differentiated non-small cell lung carcinoma, in particular, squamous cell lung carcinoma. However, p63 is not entirely specific in this distinction, as several studies have demonstrated p63 immunoreactivity in a proportion of small cell lung carcinomas. p40 (ΔNp63) has recently been purported to be a highly specific marker for squamous cell lung carcinoma, but data regarding p40 (ΔNp63) in small cell lung carcinoma, a key differential diagnostic consideration in biopsy samples of squamous cell lung carcinoma, are lacking. In this study, a total of 34 previously confirmed small cell lung carcinomas (27 bronchoscopic biopsy samples and 7 large specimens) were immunostained for p40 (ΔNp63), p63, and keratin 34βE12. All 34 small cell lung carcinomas were negative for p40 (ΔNp63) and keratin 34βE12. Although none of the large small cell lung carcinoma specimens exhibited p63 immunoreactivity, 12 (44.4%) of 27 biopsy samples of small cell lung carcinoma were positive for p63. The rate of p63 staining in small cell lung carcinoma biopsy samples differed significantly from that of p40 (ΔNp63) and keratin 34βE12 (P = .005). Ten cases of squamous cell lung carcinoma were also tested, all of which were positive for all 3 markers. These findings confirm that p63 immunoexpression is not uncommon in biopsy samples of small cell lung carcinoma. Positive p63 staining may be mistakenly interpreted as supportive of squamous differentiation and result in misclassification of small cell lung carcinoma as squamous cell lung carcinoma, a diagnostic error that has important therapeutic and prognostic consequences. To provide greater diagnostic accuracy, p40 (ΔNp63) or keratin 34βE12 should be used instead of p63 in the distinction of small cell lung carcinoma from non-small cell lung carcinoma in biopsy samples.