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 11q1...

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Bibliographic Details
Published in:	Virchows Archiv : an international journal of pathology Vol. 461; no. 2; pp. 123 - 128
Main Authors:	Choschzick, M., Tabibzada, A. M., Gieseking, F., Woelber, L., Jaenicke, F., Sauter, G., Simon, R.
Format:	Journal Article
Language:	English
Published:	Berlin/Heidelberg Springer-Verlag 01-08-2012 Springer Springer Nature B.V
Subjects:	Adult Aged Aged, 80 and over Biological and medical sciences Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - pathology Cell differentiation Chromosome aberrations Cyclin D1 - genetics Female Female genital diseases Gene Amplification Gynecology. Andrology. Obstetrics Humans Immunohistochemistry In Situ Hybridization, Fluorescence Inhibitor of Apoptosis Proteins - genetics Investigative techniques, diagnostic techniques (general aspects) Medical sciences Medicine Medicine & Public Health Middle Aged Neoplasm Grading Neoplasm Staging Original Article Pathology Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Tissue Array Analysis Tumors Ubiquitin-Protein Ligases Uterine Cervical Neoplasms - genetics Uterine Cervical Neoplasms - pathology Young Adult Amplification Cervical carcinoma c-IAP BIRC2 Malignant tumor Female genital diseases Anatomic pathology Apoptosis inhibitory protein Uterine cervix squamous cell carcinoma Cervix carcinoma Uterine cervix diseases Cervical cancer Cancer
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Summary:	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.
ISSN:	0945-6317 1432-2307
DOI:	10.1007/s00428-012-1268-1