Loss of aurora A/STK15/BTAK overexpression correlates with transition of in situ to invasive ductal carcinoma of the breast.
The biological mechanisms involved in the progression of ductal carcinoma in situ (DCIS) to invasive breast cancer are not fully understood. We previously have shown that the putative oncogene Aurora-A/STK15/BTAK, encoding a centrosome-associated kinase that regulates centrosomes and chromosome segregation, is amplified in human breast cancer. In this study, 37 archival breast tissue specimens of histologically confirmed DCIS lesions with adjacent invasive carcinoma and morphologically nonmalignant mammary ducts were analyzed immunohistochemically for expression of STK15. Statistically significant differences in overexpression of STK15 was found between invasive cancer and either nonmalignant mammary ducts (P < 0.0001) or DCIS lesions (P < 0.0005). Abnormalities in centrosome size and number was detected in the samples analyzed and 56% (14 of 25) of the cases also showed aneuploidy reflected in >2 signals of chromosome 3 and 17. Our data demonstrate that STK15 overexpression correlates with centrosome anomaly and aneuploidy in DCIS, and loss of STK15 overexpression is associated with progression of in situ to ductal invasive breast carcinoma.
Hoque
Ashraful
A
Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Carter
Jennifer
J
Xia
Weiya
W
Hung
Mien-Chie
MC
Sahin
Aysegul A
AA
Sen
Subrata
S
Lippman
Scott M
SM
D000782:Aneuploidy; D064096:Aurora Kinase A; D064127:Aurora Kinases; D014408:Biomarkers, Tumor / Q000032:analysis; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002278:Carcinoma in Situ / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D046508:Culture Techniques; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D009361:Neoplasm Invasiveness / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012494:Sampling Studies; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases