Fluorescence in situ hybridization in cervical smears: detection of numerical aberrations of chromosomes 7, 3, and X and relationship to HPV infection.
BACKGROUND
Human papillomavirus (HPV) is known to play a pivotal role in cervical carcinogenesis. Chromosomal aberrations are known to be related to different biological behaviors of malignant lesions. We analyzed whether numerical chromosomal aberrations, related to more aggressive tumor types, are found not only in high-grade squamous intraepithelial lesions (HSIL) but also in low-grade SIL (LSIL) of the cervix and evaluated their relationship to HPV infection.


METHODS
Eighty women (19 to 74 years of age) were included in this study and grouped according to the Bethesda System: within normal limits (WNL), LSIL, and HSIL. By FISH, chromosomes 7 and X, and in part chromosome 3, were analyzed for numerical aberrations. Using the hybrid capture system HPV detection was performed.


RESULTS
All 20 patients with cervical smear WNL had regular diploid chromosomal pattern and were negative for HPV. Thirteen of the 29 (41.2%) patients with LSIL showed trisomy 7, in association with trisomy X in 4 cases (12.9%). Single trisomy X was detected in 4 cases (12.9%). In 3 of 15 (20%) cases analyzed for chromosome 3 trisomy was observed. Trisomy 3 was associated with trisomy 7 and X or with trisomy 7 alone. The hybrid capture test was performed in 16 patients of this group. Two patients were positive for HPV probe A, 9 for probe B, and 2 for A and B, and 3 patients were negative. Twenty-three of the 29 patients (79.3%) with HSIL showed trisomy 7. Twelve of the 29 patients (41.3%) had an additional trisomy X. Single trisomy X was seen in only 2 cases (6. 9%). Twenty-two patients with HSIL were tested also for chromosome 3. Nine of the 22 patients (40.9%) showed trisomy 3, associated with trisomy 7 or with trisomy 7 and X. In 25 of the 29 patients HPV detection by the hybrid capture system was performed. HPV probe B was positive in 15 cases (60%). One patient was positive for both probes, A and B. Nine (36%) of the patients with HSIL were negative for both HPV probes. No positivity was observed for HPV probe A alone.


CONCLUSIONS
Our data confirm the pivotal role of HPV in cervical carcinogenesis as it seems to cause changes in the chromosomal pattern of premalignant lesions. Additionally, trisomy 7 may be considered an early event in cervical carcinogenesis, persisting and increasing with progression of the lesion. The roles of trisomy 3 and X need further evaluation.
Mian
C
C
Department of Clinical Pathology, University of Vienna, Vienna, A-1090, Austria.
Bancher
D
D
Kohlberger
P
P
Kainz
C
C
Haitel
A
A
Czerwenka
K
K
Stani
J
J
Breitenecker
G
G
Wiener
H
H
D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications / Q000821:virology*; D014412:Tumor Virus Infections / Q000150:complications / Q000821:virology*; D002583:Uterine Cervical Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D014626:Vaginal Smears; D014960:X Chromosome / Q000235:genetics*; D002578:Uterine Cervical Dysplasia / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000821:virology*