Expression of p16 and lack of pRB in primary small cell lung cancer

Abstract

The retinoblastoma protein (pRB), p16, and cyclin D1 are major components of the RB pathway, which controls the G1 checkpoint of the cell cycle. Proper regulation of this pathway is crucial for normal cell proliferation. Abnormal forms of these proteins have been found in various types of malignant tumours. In the present report, immunohistochemical techniques were applied to study the expression of pRB, p16, and cyclin D1 in 161 samples of primary small cell lung cancer (SCLC) and 20 samples of non‐small cell lung cancer (NSCLC). While pRB and cyclin D1 staining was negative in 161 specimens of SCLC, expression of p16 was observed in 153 samples. In contrast to SCLC, 16 out of 20 NSCLC cases exhibited pRB expression and 15 showed cyclin D1 expression, but only very weak p16 staining was found in five samples. These observations could provide additional criteria for the distinction between SCLC and NSCLC. Furthermore, these findings, based on primary tissues, implicate different mechanisms in the tumourigenesis of SCLC and NSCLC. Copyright © 1999 John Wiley & Sons, Ltd.

Detection of Overexpressed and Phosphorylated Wild-Type Kit Receptor in Surgical Specimens of Small Cell Lung Cancer

“…In addition, it is well known that the deregulation of a number of other genes contributes to the growth of this complex tumor (28,29).…”

The meaning of p16ink4aexpression in tumors

“…36 Therefore, at present there are two complementary models for the appearance of tumors with high levels adenocarcinoma with low levels of p16 ink4a . 43,44 While these are histologically distinct forms of disease, the discriminatory capacity of p16 ink4a levels is also significant in defining subtypes of histologically indistinguishable disease. For example, in head and neck cancers those with a specific viral etiology can be defined by p16 ink4a levels and represent a particular clinical manifestation of disease.…”

A chimeric fusion of the hASH1 and EZH2 promoters mediates high and specific reporter and suicide gene expression and cytotoxicity in small cell lung cancer cells

“…21 Inactivation of Rb by diverse mechanisms such as gene deletion, mutation or aberrant post-transcriptional regulation has long been considered a hallmark of SCLC. [24][25][26] Furthermore, and in concordance with the lack of Rb expression, overexpression of E2F1 and E2F3 has been reported in the majority of SCLC. 27,28 The EZH2 expression status in SCLC remains to be determined, but the lack of Rb signaling with subsequent upregulation of E2Fs in SCLC suggests that EZH2 gene expression could be upregulated in SCLC cells.…”

“…21,34 Furthermore, Rb is very frequently mutated or inactivated in SCLC. [24][25][26] We therefore evaluated the Rb expression and phosphorylation status in the SCLC and control cell lines by western blot analysis. Of all the SCLC cell lines, active Rb could only be detected in DMS273, the only SCLC cell line with low EZH2 activity, while the inactive hyperphosphorylated form of Rb was detected in DMS53 and no Rb in the remaining SCLC cell lines (Figure 4c).…”