BIRC2 amplification in squamous cell carcinomas of the uterine cervix.
Oncogene amplification is a key step in cell transformation towards malignancy. Chromosomal aberrations involving the long arm of chromosome 11, including amplifications at 11q13 and 11q22, have been previously reported in cervical cancer. While the role of the CCND1 gene as the driver gene for 11q13 amplification is well established in different tumor types, the significance of the 11q22 amplicon is less clear. The 11q22 amplicon corresponds to several putative target genes including the apoptose inhibitor BIRC2, recently detected as amplified in cervical cancer cell lines. To better understand the distribution and frequency of 11q amplification sites in uterine cervical carcinomas, we analyzed BIRC2 and CCND1 copy number changes using fluorescence in situ hybridization in a tissue microarray containing 238 cervical cancers. High-level amplification of BIRC2 was found in 12.9 % of tumors. Amplification of BIRC2 in cervical carcinomas was homogeneous as shown in corresponding whole tissue sections of amplified tumors at the tissue microarray. BIRC2 amplification was significantly more frequent than CCND1 amplification (2.1 %) in our cohort (p < 0.01), and amplification of both genes were independent from each other. BIRC2 amplification was associated with younger-patient age (p < 0.05) and squamous cell differentiation (p = 0.025) of cervix carcinomas. However, BIRC2 copy number changes were not related to tumor stage, grading and nodal status of cervical cancers. In conclusion, BIRC2 is amplified in a subset of squamous cell carcinoma of the uterine cervix. Further studies are necessary to evaluate possible prognostic effects of BIRC2 copy number gains in cervical carcinomas.
Department of Pathology, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. mchoschz@uke.uni-hamburg.de
M
M
Choschzick
A M
AM
Tabibzada
F
F
Gieseking
L
L
Woelber
F
F
Jaenicke
G
G
Sauter
R
R
Simon
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D046888:Tissue Array Analysis; D044767:Ubiquitin-Protein Ligases; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
C530104:CCND1 protein, human; D051034:Inhibitor of Apoptosis Proteins; D019938:Cyclin D1; C494833:BIRC2 protein, human; D044767:Ubiquitin-Protein Ligases