We compared diagnostic performance of INSM1 and previously reported composite marker CD56 + p16 + thyroid transcription factor-1 (TTF1) in the diagnosis of SCLC in small biopsy specimens and cytoblocks.
Using PDX, we show proof-of-concept that a high ratio of p16 to cyclin D1 gene expression reflects underlying Rb functional loss and distinguishes morphologically identified small-cell carcinoma from prostatic adenocarcinoma in patient specimens (n = 13 and 9, respectively).
In our study, we investigated polyomavirus infection (SV40 and MCPyV) and promoter hypermethylation of the tumour suppressors RASSF1A and p16 in 18 SCLCs (14 primaries and 4 regional lymph node metastases) and 18 blood control samples.
Mutation at p16 occurred more frequently in non-small cell lung cancer (19.3%) than in small cell lung cancer (5.4%); while the mutation rate of Rb was 32.4% in small cell lung cancer versus 2.3% in non-small cell lung cancer.
One hundred and fifty specimens from cancerous and adjacent non-cancerous tissue, bronchial washings and sputum from patients and 48 specimens, mostly sputum, from disease-free smokers were included. p16 methylation was very frequent in biopsies (82.85%) and bronchial washings (non-small cell lung carcinoma, 80.35%; small cell lung carcinoma, 16.66%) from patients, but also in adjacent non-cancerous tissue (45.71%).
The frequencies of the expressions of CD56, mASH1, TTF-1, and p16 were higher and that of NeuroD was lower in small cell carcinoma than in large cell neuroendocrine carcinoma.
Our data confirm the predicted reciprocity between Rb inactivation and p16 expression in a common human malignancy and define differential p16 expression as a fundamental distinction between NSCLC and SCLC.