Amplification and expression of the cyclin D1 gene in anal and esophageal squamous cell carcinomas.
Cyclin D1 is a cell-cycle regulator and candidate proto-oncogene implicated in the pathogenesis of numerous tumor types. Amplification of the cyclin D1 gene occurs commonly in esophageal squamous cell carcinomas. However, no studies have examined the role of cyclin D1 in anal carcinogenesis. We examined 20 esophageal squamous cell carcinomas and 24 anal carcinomas for cyclin D1 alterations. Protein expression was evaluated by immunohistochemistry using the cyclin DIGM antibody (Novocastra, Newcastle upon Tyne, UK). Cyclin D1 amplification was examined by fluorescent in situ hybridization (FISH), using a cyclin D1 probe obtained from Toshiya Inaba at St. Jude Children's Research Hospital, Memphis, TN. The FISH sections were analyzed using a Leica (Deerfield, IL) confocal microscope. By immunohistochemistry, 75% of esophageal carcinomas showed evidence of cyclin D1 expression. Cyclin D1 amplification was detected by FISH in 65% of esophageal cancers. There was good correlation between cyclin D1 protein expression and gene amplification, although some tumors showed protein overexpression in the absence of gene amplification. Among the 24 anal carcinomas studied, 8% showed weak cyclin D1 immunoreactivity in rare tumor cells. None of the anal tumors showed cyclin D1 amplification. We conclude that cyclin D1 alterations are common in esophageal carcinomas but do not appear to be important in anal carcinogenesis. Immunohistochemical detection of cyclin D1 protein overexpression is a good predictor of cyclin D1 amplification.
Sheyn
I
I
Department of Pathology, University of Cincinnati, OH 45267-0529, USA.
Noffsinger
A E
AE
Heffelfinger
S
S
Davis
B
B
Miller
M A
MA
Fenoglio-Preiser
C M
CM
D001005:Anus Neoplasms / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D019938:Cyclin D1; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D000090063:Proto-Oncogene Mas
D016213:Cyclins; C000715470:MAS1 protein, human; D015513:Oncogene Proteins; D000090063:Proto-Oncogene Mas; D019938:Cyclin D1