Biological and clinical significance of loss of heterozygosity at the INPP4B gene locus in Japanese breast cancer |
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| Affiliation: | 1. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;2. Department of Molecular Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;3. Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;4. Department of Breast Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan;1. Department of Human Oncology, University of Wisconsin, Madison, WI;2. Department of Radiation Oncology, UCLA Health, Los Angeles, CA;3. Department of Radiation Oncology, William Beaumont Hospital, William Beaumont School of Medicine, Oakland University, Royal Oak, MI;4. Gamma West Cancer Services, Salt Lake Regional Medical Center, Salt Lake City, UT;5. Arizona Breast Cancer Specialists, Scottsdale, AZ;1. Department of Surgery, Mayo Clinic, Phoenix, AZ;2. Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN;3. Department of Diagnostic Radiology, Phoenix, AZ;4. Department of Medical Oncology, Mayo Clinic, Phoenix, AZ;5. Department of Anatomic Pathology, Mayo Clinic, Phoenix, AZ;6. Department of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ;1. Department of Radiation Oncology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK;2. Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK;1. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Dei Tumouri di Milano, Milano, Italy;2. Department of Oncology, Istituto Oncologico Veneto, IRCCS, Padua, Italy;3. Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy;4. Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy;5. Vall D''Hebron University Hospital (HUVH) and Vall D''Hebron Institute of Oncology (VHIO), Barcelona, Spain;6. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center;7. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University, School of Medicine, South Korea;8. Department of Medicine (DIMED), Surgical Pathology Unit, University of Padua, Padua, Italy;9. Medical Oncology Unit, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy;10. Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale Dei Tumouri di Milano, Milan, Italy;1. Department of Pharmacy Practice and Science, College of Pharmacy, Iowa City, IA;2. Department of Epidemiology, College of Public Health, Iowa City, IA;3. Division of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, Carver College of Medicine, Iowa City, IA |
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| Abstract: | PurposeINPP4B is considered to function as a putative tumor suppressor through its inhibitory function of Akt. In various malignant tumors, loss of heterozygosity (LOH) at the chromosomal region containing INPP4B and lower expression of INPP4B has been reported. The purpose of this study was to examine the frequency of the INPP4B LOH and its association with the clinicopathological characteristics and prognosis in breast cancer of Japanese women.MethodsThe allelic alteration at the INPP4B and PTEN gene loci was analyzed in 277 invasive primary breast carcinomas. The relationships between INPP4B LOH and the clinicopathological features were investigated.ResultsAmong the 238 informative cases for the evaluation, LOH at the INPP4B gene locus was observed in 43 tumors (18.1%). INPP4B LOH was significantly correlated with ER and PR negativity (p = 0.0009 and p = 0.0029, respectively), higher nuclear grade (p < 0.0001), higher Ki67 labeling index (p = 0.0006), triple-negative (TN) subtype (p = 0.0005) and PTEN LOH (p < 0.0001). INPP4B LOH was significantly associated with poorer prognosis, in terms of the relapse-free survival (RFS) and overall survival (OS). According to the multivariate analyses, INPP4B LOH was not independently associated with the prognosis.ConclusionThe incidence of INPP4B LOH was significantly higher in the TN subtype and positively correlated with PTEN LOH. INPP4B LOH was associated with more aggressive and proliferative phenotype. INPP4B LOH was also associated with poorer prognosis. |
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| Keywords: | INPP4B PTEN Loss of heterozygosity Breast cancer Triple-negative breast cancer LOH" },{" #name" :" keyword" ," $" :{" id" :" kwrd0040" }," $$" :[{" #name" :" text" ," _" :" loss of heterozygosity ROH" },{" #name" :" keyword" ," $" :{" id" :" kwrd0050" }," $$" :[{" #name" :" text" ," _" :" retention of heterozygosity INPP4B" },{" #name" :" keyword" ," $" :{" id" :" kwrd0060" }," $$" :[{" #name" :" text" ," _" :" Inositol polyphosphate 4-phosphatase type II PI3K" },{" #name" :" keyword" ," $" :{" id" :" kwrd0070" }," $$" :[{" #name" :" text" ," _" :" phosphoinositide 3-kinase PTEN" },{" #name" :" keyword" ," $" :{" id" :" kwrd0080" }," $$" :[{" #name" :" text" ," _" :" phosphatase and tensin homolog TNBC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0090" }," $$" :[{" #name" :" text" ," _" :" triple negative breast cancer RFS" },{" #name" :" keyword" ," $" :{" id" :" kwrd0100" }," $$" :[{" #name" :" text" ," _" :" relapse-free survival DMFS" },{" #name" :" keyword" ," $" :{" id" :" kwrd0110" }," $$" :[{" #name" :" text" ," _" :" distant metastasis-free survival OS" },{" #name" :" keyword" ," $" :{" id" :" kwrd0120" }," $$" :[{" #name" :" text" ," _" :" overall survival |
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