Allelic losses at chromosome 3p are seen in human papilloma virus 16 associated transitional cell carcinoma of the cervix.
OBJECTIVE
Transitional cell carcinomas (TCCs) of the cervix are rare neoplasms of the female genital tract. Although these tumors display urothelial differentiation, there is controversy regarding their histogenetic relationship to squamous cell carcinomas (SCC) of the cervix versus transitional cell carcinomas of the bladder.


METHODS
We performed partial allelotyping of five TCCs of the cervix using 23 polymorphic markers located on chromosomes 3p and 9, which demonstrate frequent and early losses in cervical SCC and urothelial TCC, respectively. Multiplex polymerase chain reaction was used on DNA extracted from archival paraffin-embedded tissue using precise microdissection. Additionally, P53 gene mutation analysis was performed using single-strand confirmation polymorphism (SSCP) and the presence of human papilloma virus (HPV) sequences was analyzed using general and specific (types 16 and 18) primers.


RESULTS
General HPV sequences were demonstrated in all cases, but the oncogenic strain HPV 16 was present in only three (60%) of the five tumors; no HPV 18 was detected in any sample. Three of five TCCs, all harboring HPV 16 sequences, demonstrated concurrent allelic losses at several 3p loci (specifically 3p12, 3p14.2 [the FHIT gene locus], 3p21.3, and 3p22-24.2). LOH at a single locus on 9q32-qter was demonstrated in one tumor; no other deletions were seen on chromosome 9. P53 gene mutations in exons 5-8 were absent by SSCP analysis.


CONCLUSIONS
The infrequent involvement of chromosome 9 in TCCs of the cervix, along with the concurrent presence of 3p LOH and oncogenic HPV 16 in a subset of tumors, suggests a closer histogenetic relationship of this neoplasm to cervical SCCs rather than urothelial TCCs.
Maitra
A
A
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, 75235, USA.
Wistuba
I I
II
Gibbons
D
D
Gazdar
A F
AF
Albores-Saavedra
J
J
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000821:virology; D002295:Carcinoma, Transitional Cell / Q000737:chemistry / Q000235:genetics* / Q000821:virology*; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000821:virology*
D004279:DNA, Viral