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Background. Oncogene activation and tumor suppressor gene inactivation have been implicated in the genetic basis of esophageal squamous cell carcinoma (ESCC). Cyclin D1, an oncogene that has a critical role in G1 progression of the cell cycle, has been observed to be amplified in carcinomas of the breast and head and neck, and translocated in parathyroid adenomas and centrocytic lymphomas. Methods. Established ESCC cell lines were assayed for cyclin D1 amplification and overexpression by Southern, Northern, and Western blot analyses. In addition, cyclin D1 overexpression was determined in primary tumors and adjacent normal mucosa by differential polymerase chain reaction (PCR) and immunohistochemical staining. Results. The authors observed that approximately 50% of ESCC cell lines with cyclin D1 DNA amplification also had RNA and protein overexpression. Related genes, cyclin D2 and D3, were not amplified or overexpressed in these cell lines with rare exception. The cyclin D1 protein was able to associate with the cell-cycle-dependent kinases, cdk4 and cdk6, but not always with proliferating cell nuclear antigen in selected cell lines tested, representing a novel finding. In addition, approximately 50% of primary tumors had cyclin D1 overexpression that was not present in adjacent normal mucosa. Cyclin D1 overexpression based on PCR correlated with enhanced cyclin D1 protein nuclear staining in malignant cells. Conclusion. Cyclin D1 is amplified and overexpressed in ESCC and may be important in its molecular pathogenesis. Cancer 1995; 76:541-9. Key words: cyclin D1, oncogene, esophageal squamous cell carcinoma, polymerase chain reaction, gene amplification.

Background. Alterations in the tumor suppressor gene p53 are the most frequently detected genetic abnormalities in human cancers. Inactivated tumor suppressor genes, including p53, often are suggested by loss of heterozygosity (LOH) studies. p53 gene inactivation has been reported in esophageal cancers. Because the etiologic factors for esophageal and intraoral carcinomas often are the same, corresponding molecular events may occur in oral squamous cell carcinoma (SCC) development. Methods. The authors investigated LOH of the p53 gene in DNA from 27 primary oral cancers using a polymerase chain reaction (PCR)-based restriction fragment length polymorphism assay. DNA from fixed specimens of SCC and normal tissues was isolated and amplified at two p53 gene polymorphic restriction sites. Results. In heterozygous individuals, 10 of 14(71%) intraoral SCC demonstrated loss of p53 heterozygosity at one polymorphic restriction site. Two of five carcinomas showed LOH at a second site. Conclusions. These results suggest that inactivation of p53 is involved in the development or progression of SCC of the oral cavity. Cancer 1993; 71:1933-7.