Expression of P40 and P63 in lung cancers using fine needle aspiration cases. Understanding clinical pitfalls and limitations

Background: Fine-needle aspiration (FNA) biopsy of lung lesions is a highly accurate method for diagnosing and staging of lung cancers, particularly in patients with advanced cancer. Although, the majority of FNA cases of non-small cell lung carcinoma (NSCLC) can be subclassified by hematoxylin and eosin (H&E) sections, immunohistochemical (IHC) markers are usually necessary for difficult cases. Our previous study has shown that both P40 and P63 demonstrate differential sensitivity and specificity in the subclassification of squamous cell carcinoma (SqCC) using tumor tissue microarrays (TMA). In the present study, we further evaluated the utility of P40 and P63 and the potential pitfalls and limitations associated with the usefulness of these stains in FNA cases.

Methods: By a computer search of pathology archives, 144 FNA biopsies with diagnoses of lung cancers and P40/P63 stains were identified, including 50 adenocarcinomas (ADCs), 56 SqCCs, 8 small cell lung carcinomas (SCLCs), and 12 cases of poorly differentiated carcinoma (PD CA). Ten benign FNA lung lesions and 8 other malignant neoplasms were also included as controls. Nuclear staining patterns of P40 and P63 were scored semi-quantitatively as 0 (negative), 1 (<10%, weak and focal), or 2 (>10%, strong and diffuse).

Results: In lung SqCCs, P40 and P63 were positive in 77.3% and 89.5% cases, respectively. In ADCs, P40 was weakly and focally positive in 6.1% cases, and P63 was variably positive in 62.8% cases. In SCLCs, P40 and P63 were focally positive in 12.5% and 50% cases. In PD CAs, no P40 or P63 immunoreactivity was detected. In the group of other neoplasms (n=8) both P40 and P63 were positive in the case of metastatic non-seminomatous germ cell tumor (NSGCT) (n=1), and P63 was positive in the case of metastatic Merkel cell carcinoma (n=1). The sensitivity and specificity of P40 and P63 were 76.9%/93.3%, and 90.2%/50.7% in the lung SqCC.

Conclusions: P63 has a better sensitivity, and P40 has a better specificity for SqCC. A positive staining pattern with both markers was also found in certain non-SqCC cases. Recognizing limitations of these markers are particularly important in FNA cases.