Lonardo F, Rusch V, Langenfeld J, Dmitrovsky E, Klimstra D S
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Cancer Res. 1999 May 15;59(10):2470-6.
Increased protein expression of the G1 cyclins D1 and E is reported in invasive non-small cell lung carcinoma. However, during transformation of the bronchial epithelium, overexpression of these species occurs, and their relationship to aberrant expression of p53 and retinoblastoma (Rb) has not been described previously. To determine the expression of these cell cycle regulators during the development of invasive squamous cell carcinoma (SCC) of the lung, the immunohistochemical expression patterns in normal bronchial epithelium (n = 36), squamous metaplasia (SM; n = 28), and epithelial atypia (n = 34) were compared with that in low-grade dysplasia (LGD; n = 17), high-grade bronchial dysplasia (HGD; n = 30), and SCC (n = 36). Monoclonal anti-p53 Pab1801, polyclonal anti-cyclin D1 DCS6, monoclonal anti-cyclin E HE12, and monoclonal anti-Rb OP-66 antibodies were used. Cyclin D1 was not expressed in normal bronchial epithelium but was detected in 7% of SMs, 15% of atypias; 18% of LGDs, 47% of HGDs, and 42% of SCCs. Cyclin E was not detected in normal epithelium (n = 24), SM (n = 16), or LGD (n = 12), but it was found in 9% of atypias (2 of 22), 33% of HGDs (7 of 21), and 54% of SCCs (13 of 24). p53 was not expressed in normal epithelium, SM, and LGD, but it was overexpressed in 6% of atypias, 53% of HGDs, and 61% of SCCs. Abnormal Rb expression was found only in 2 of 36 cases of SCC. A total of 91% of HGDs and 92% of SCCs exhibited overexpression of at least one of the p53, cyclin D1, or cyclin E species. However, no link was observed between overexpression of p53 and the overexpressed G1 cyclins in preneoplastic lesions. Overexpression of cyclin D1, cyclin E, and p53 occurs frequently and independently in pulmonary SCC and is detected in lesions before the development of invasive carcinoma. In contrast, altered Rb expression is a late and infrequent event in squamous cell carcinogenesis.
据报道，侵袭性非小细胞肺癌中G1细胞周期蛋白D1和E的蛋白表达增加。然而，在支气管上皮转化过程中，这些蛋白会出现过表达，且它们与p53和视网膜母细胞瘤（Rb）异常表达的关系此前尚未见描述。为了确定这些细胞周期调节因子在肺侵袭性鳞状细胞癌（SCC）发生过程中的表达情况，将正常支气管上皮（n = 36）、鳞状化生（SM；n = 28）和上皮异型增生（n = 34）中的免疫组化表达模式与低级别发育异常（LGD；n = 17）、高级别支气管发育异常（HGD；n = 30）和SCC（n = 36）中的进行了比较。使用了单克隆抗p53 Pab1801、多克隆抗细胞周期蛋白D1 DCS6、单克隆抗细胞周期蛋白E HE12和单克隆抗Rb OP - 66抗体。细胞周期蛋白D1在正常支气管上皮中未表达，但在7%的鳞状化生、15%的异型增生、18%的低级别发育异常、47%的高级别发育异常和42%的鳞状细胞癌中被检测到。细胞周期蛋白E在正常上皮（n = 24）、鳞状化生（n = 16）或低级别发育异常（n = 12）中未被检测到，但在9%的异型增生（22例中的2例）、33%的高级别发育异常（21例中的7例）和54%的鳞状细胞癌（24例中的13例）中被发现。p53在正常上皮、鳞状化生和低级别发育异常中未表达，但在6%的异型增生、53%的高级别发育异常和61% 的鳞状细胞癌中过表达。仅在36例鳞状细胞癌中的2例发现Rb表达异常。91%的高级别发育异常和92%的鳞状细胞癌表现出p53、细胞周期蛋白D1或细胞周期蛋白E中至少一种的过表达。然而，在癌前病变中未观察到p53过表达与过表达的G1细胞周期蛋白之间的联系。细胞周期蛋白D1、细胞周期蛋白E和p53的过表达在肺鳞状细胞癌中频繁且独立发生，并在侵袭性癌发生之前的病变中被检测到。相比之下，Rb表达改变在鳞状细胞癌发生过程中是一个较晚且不常见的事件。
