Genomic aberrations in invasive cervical cancer

Purpose: Cervical carcinomas are almost always squamous cell carcinomas, whereas adenocarcinomas are rare. There is evidence that specific genetic events are involved in initiation and progression of invasive cervical cancer. The genotype-phenotype correlations in cervical cancer are unclear. Material and Methods: Comparative genomic hybridization was applied to screen for DNA copy number changes in 62 squamous cell carcinomas and 22 adenocarcinomas of clinical stage 1B. Immunohistochemistry was performed in adenocarcinoma samples to determine the HER-2 expression (HercepTest(TM)). Results: In both cancer types, DNA sequence losses were most prevalent at chromosomes 4 q, Xq and 18 q. Losses were the most frequent alterations in squamous cell carcinoma, whereas DNA sequence gains of chromosome 17 q (54%) represented the most frequent copy number alterations in cervical adenocarcinomas. HER-2 overexpression was detected in only two adenocarcinomas. The total number of DNA aberrations per tumor (P > 0.02), and the number of DNA sequence losses per tumor (P > 0.04) were associated with disease-specific survival in squamous cell carcinoma. 9 p deletions were significantly more frequent in squamous cell carcinomas with lymph node metastasis than in node negative tumors (P > 0.03). Losses of chromosome 11 p (P > 0.0001) and 18 q (P > 0.01) were associated with poor prognosis in squamous cell carcinomas without lymph node metastasis. In analogy to squamous cell carcinoma, DNA sequence losses of chromosome 18 q were significantly associated with poor prognosis in cervical adenocarcinoma (P > 0.01). Conclusion: DNA sequence copy number gains on 17 q are not associated with HER-2 expression in adenocarcinomas. The inactivation of tumor suppressor genes on chromosome 18 q might be responsible for the progression of both cervical adenocarcinoma and squamous cell carcinoma.