Human papillomavirus and mutated H-ras oncogene in cervical carcinomas and pathological negative pelvic lymph nodes: a retrospective follow-up.
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.
Landro
María Eulalia
ME
Servicio Virus Oncogénicos, Departamento Virología, Instituto Nacional de Enfermedades Infecciosas, ANLIS Carlos G. Malbrán, Buenos Aires, Argentina.
Dalbert
Delia
D
Picconi
María Alejandra
MA
Cúneo
Nicasio
N
González
Joaquín
J
Vornetti
Silvia
S
Bazán
Graciela
G
Mural
Juan
J
Basiletti
Jorge
J
Teyssié
Angélica Rita
AR
Alonio
Lidia Virginia
LV
D000328:Adult; D000368:Aged; D002467:Cell Nucleus / Q000821:virology; D003593:Cytoplasm / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D042783:Endothelial Cells / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D011905:Genes, ras; D052162:Human papillomavirus 16 / Q000302:isolation & purification; D052161:Human papillomavirus 18 / Q000302:isolation & purification; D006801:Humans; D017403:In Situ Hybridization; D008198:Lymph Nodes / Q000821:virology*; D008214:Lymphocytes / Q000821:virology; D008264:Macrophages / Q000821:virology; D008875:Middle Aged; D009154:Mutation; D030361:Papillomavirus Infections / Q000821:virology*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012189:Retrospective Studies; D017154:Stromal Cells / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000821:virology*
D004279:DNA, Viral