Human papillomavirus and mutated H-ras oncogene in cervical carcinomas and pathological negative pelvic lymph nodes: A retrospective follow-up

• Published in: Journal of medical virology 2008-04, Vol.80 (4), p.694-701
• Main Authors: Landro, María Eulalia, Dalbert, Delia, Picconi, María Alejandra, Cúneo, Nicasio, González, Joaquín, Vornetti, Silvia, Bazán, Graciela, Mural, Juan, Basiletti, Jorge, Teyssié, Angélica Rita, Alonio, Lidia Virginia
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Cell Nucleus - virology; cervical cancer; co-factor; Cytoplasm - virology; DNA, Viral - genetics; Endothelial Cells - virology; Female; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; Genes, ras; H-ras oncogene; HPV; Human papillomavirus; Human papillomavirus 16 - isolation & purification; Human papillomavirus 18 - isolation & purification; Human viral diseases; Humans; In Situ Hybridization; Infectious diseases; lymph node; Lymph Nodes - virology; Lymphocytes - virology; Macrophages - virology; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Mutation; Papillomavirus Infections - virology; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Retrospective Studies; Stromal Cells - virology; subclinical metastasis; Uterine Cervical Neoplasms - virology; Viral diseases; Virology
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.21076

The metastasis status of pelvic lymph nodes (PLNs) seems to be a predictive factor of survival. It was suggested that the presence of HPV DNA and other biological markers in PLN may indicate a sub clinical early metastasis. The aim was to describe the prevalence and distribution patterns of HPV DNA and H‐ras mutations in intra operatively obtained cervical tumors and PLN. Thirty‐seven cervical tumors and 61 lymph node biopsies from 37 patients with cervical cancer were selected. HPV typing and location were performed by PCR/dot blot and in situ hybridization (ISH) respectively. PCR/RFLP was used to scan for mutations in H‐ras. Hundred percent of the cervical cancers and 85% of the PLN were HPV positive; co‐infection with more than one type was 27%. HPV 16 was detected alone or co‐infecting with other types in 84% of tumors and 46% of PLN; the second most frequent viral type was HPV 18 (tumor: 27%; PLN: 20%). In PLN, HPV was located in nuclei or/and cytoplasm of lymphocytes, macrophages, endothelial, and /or stromal cells. H‐ras mutations were identified in 5/24 (21%) of patients with cervical tumors showing poor or moderated differentiation. HPV DNA in histological tumor‐free PLN not necessary indicate metastasis, but it may be associated to an active immune reaction. Mutated H‐ras is probably involved in cervical carcinogenesis and its detection in tumor and metastasis free PLN may be related to early metastasis or recurrence in at least a subset of poorly differentiated cervical tumors. J. Med. Virol. 80:694–701, 2008. © 2008 Wiley‐Liss, Inc.