BACKGROUND: Annexin A1 (ANXA1) is a potential marker of development of breast cancer. However, previous studies of ANXA1 expression in primary breast carcinoma and lymph node metastasis have yielded conflicting results. Therefore, to accurately characterize the ANXA1 expression pattern, we used microarray analysis and matched patient samples to evaluate progressive alterations in ANXA1 protein expression during malignant transformation and metastasis. DESIGN: We constructed a tissue microarray using 82 pairs of primary breast cancers and lymph node metastases from archival materials. We also identified 21 cases of breast carcinoma for which a single slide contained the entire progression from benign breast tissue, carcinoma in situ, to invasive carcinoma. Immunohistochemical staining for ANXA1 and various prognostic markers was performed. RESULT: Microarray analysis revealed that ANXA1 expression was lost in 79% of breast carcinomas, and there was no difference in ANXA1 expression between primary breast carcinoma and lymph node metastasis. Most ANXA1-negative tumors were positive for estrogen and progesterone receptors but negative for HER2/neu and epidermal growth factor receptor. In contrast, most ANXA1-positive tumors were negative for estrogen, progesterone, and HER2/neu. In the whole tissue sections, ANXA1 is heterogeneously expressed in benign epithelium and is lost in both in situ carcinoma and invasive carcinoma. CONCLUSIONS: The lack of ANXA1 expression in the majority of breast carcinomas and the early loss of ANXA1 expression in in situ carcinoma, which is maintained in both invasive and metastatic tumors, suggests a possible role for ANXA1 in the early events of malignant transformation.
BACKGROUND:Annexin A1 (ANXA1) is a potential marker of development of breast cancer. However, previous studies of ANXA1 expression in primary breast carcinoma and lymph node metastasis have yielded conflicting results. Therefore, to accurately characterize the ANXA1 expression pattern, we used microarray analysis and matched patient samples to evaluate progressive alterations in ANXA1 protein expression during malignant transformation and metastasis. DESIGN: We constructed a tissue microarray using 82 pairs of primary breast cancers and lymph node metastases from archival materials. We also identified 21 cases of breast carcinoma for which a single slide contained the entire progression from benign breast tissue, carcinoma in situ, to invasive carcinoma. Immunohistochemical staining for ANXA1 and various prognostic markers was performed. RESULT: Microarray analysis revealed that ANXA1 expression was lost in 79% of breast carcinomas, and there was no difference in ANXA1 expression between primary breast carcinoma and lymph node metastasis. Most ANXA1-negative tumors were positive for estrogen and progesterone receptors but negative for HER2/neu and epidermal growth factor receptor. In contrast, most ANXA1-positive tumors were negative for estrogen, progesterone, and HER2/neu. In the whole tissue sections, ANXA1 is heterogeneously expressed in benign epithelium and is lost in both in situ carcinoma and invasive carcinoma. CONCLUSIONS: The lack of ANXA1 expression in the majority of breast carcinomas and the early loss of ANXA1 expression in in situ carcinoma, which is maintained in both invasive and metastatic tumors, suggests a possible role for ANXA1 in the early events of malignant transformation.
Authors: Aaron E Hoffman; Chun-Hui Yi; Tongzhang Zheng; Richard G Stevens; Derek Leaderer; Yawei Zhang; Theodore R Holford; Johnni Hansen; Jennifer Paulson; Yong Zhu Journal: Cancer Res Date: 2010-02-02 Impact factor: 12.701
Authors: Frida Danielsson; Marie Skogs; Mikael Huss; Elton Rexhepaj; Gillian O'Hurley; Daniel Klevebring; Fredrik Pontén; Annica K B Gad; Mathias Uhlén; Emma Lundberg Journal: Proc Natl Acad Sci U S A Date: 2013-04-08 Impact factor: 11.205
Authors: Marcelo Sobral-Leite; Jelle Wesseling; Vincent T H B M Smit; Heli Nevanlinna; Martine H van Miltenburg; Joyce Sanders; Ingrid Hofland; Fiona M Blows; Penny Coulson; Gazinska Patrycja; Jan H M Schellens; Rainer Fagerholm; Päivi Heikkilä; Kristiina Aittomäki; Carl Blomqvist; Elena Provenzano; Hamid Raza Ali; Jonine Figueroa; Mark Sherman; Jolanta Lissowska; Arto Mannermaa; Vesa Kataja; Veli-Matti Kosma; Jaana M Hartikainen; Kelly-Anne Phillips; Fergus J Couch; Janet E Olson; Celine Vachon; Daniel Visscher; Hermann Brenner; Katja Butterbach; Volker Arndt; Bernd Holleczek; Maartje J Hooning; Antoinette Hollestelle; John W M Martens; Carolien H M van Deurzen; Bob van de Water; Annegien Broeks; Jenny Chang-Claude; Georgia Chenevix-Trench; Douglas F Easton; Paul D P Pharoah; Montserrat García-Closas; Marjo de Graauw; Marjanka K Schmidt Journal: BMC Med Date: 2015-07-02 Impact factor: 8.775