Annexin A1 down-regulation in head and neck cancer is associated with epithelial differentiation status.

Annexin A1 (ANXA1) protein expression was evaluated by Western blot in a series of 32 head and neck squamous cell carcinomas (HNSCCs) in a search for molecular alterations that could serve as useful diagnostic/prognostic markers. ANXA1 down-regulation was observed in 24 cases (75%) compared with patient-matched normal epithelium. In relation to clinicopathological variables, ANXA1 down-regulation was significantly associated with advanced T stages (P = 0.029), locoregional lymph node metastases (P = 0.038), advanced disease stage (P = 0.006), hypopharyngeal localization (P = 0.038), and poor histological differentiation (P = 0.005). ANXA1 expression was also analyzed by immunohistochemistry in paraffin-embedded sections from 22 of 32 HNSCCs and 8 premalignant lesions. All dysplastic tissues showed significantly reduced ANXA1 expression compared to a strong positive signal observed in adjacent normal epithelia (except basal and suprabasal cells). A close association was observed between ANXA1 expression and the histological grade in HNSCC. Well-differentiated tumors presented a positive ANXA1 signal in highly keratinized areas whereas moderately and poorly differentiated tumors exhibited very weak or negative staining. Our findings clearly identify ANXA1 as an effective differentiation marker for the histopathological grading of HNSCCs and for the detection of epithelial dysplasia.

[1]  M. Paul-Clark,et al.  The FASEB Journal express article 10.1096/fj.02-0239fje. Published online December 3, 2002. Aberrant inflammation and resistance to glucocorticoids in Annexin 1 –/ – Mouse , 2022 .

[2]  Ming-Rong Wang,et al.  Three isoforms of annexin I are preferentially expressed in normal esophageal epithelia but down-regulated in esophageal squamous cell carcinomas , 2002, Oncogene.

[3]  M. Israel,et al.  Annexin II marks astrocytic brain tumors of high histologic grade. , 1994, Oncology research.

[4]  Alejandro A Schäffer,et al.  Genetic differences detected by comparative genomic hybridization in head and neck squamous cell carcinomas from different tumor sites: construction of oncogenetic trees for tumor progression , 2002, Genes, chromosomes & cancer.

[5]  J. Trent,et al.  Analysis of genetic alterations in primary nasopharyngeal carcinoma by comparative genomic hybridization , 2001, Genes, chromosomes & cancer.

[6]  J. Califano,et al.  11:40 AM: A Genetic Progression Model for Head and Neck Cancer: Implications for Field Cancerization , 1996 .

[7]  H. Asada,et al.  Annexin VII as a Novel Marker for Invasive Phenotype of Malignant Melanoma , 2000, Japanese journal of cancer research : Gann.

[8]  O. Kallioniemi,et al.  ANX7, a candidate tumor suppressor gene for prostate cancer , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[9]  A. Hanby,et al.  Identification by differential display of annexin-VI, a gene differentially expressed during melanoma progression. , 1996, Cancer research.

[10]  Li Mao,et al.  Identification and validation of metastasis-associated proteins in head and neck cancer cell lines by two-dimensional electrophoresis and mass spectrometry , 2004, Clinical & Experimental Metastasis.

[11]  S. Clark,et al.  Loss of annexin II heavy and light chains in prostate cancer and its precursors. , 2001, Cancer research.

[12]  N. Copeland,et al.  Novel human and mouse annexin A10 are linked to the genome duplications during early chordate evolution. , 1999, Genomics.

[13]  Chi-Hung Lin,et al.  Comparative genomic hybridization of esophageal squamous cell carcinoma , 2001, Cancer.

[14]  Maria D Person,et al.  Annexin II expression is reduced or lost in prostate cancer cells and its re-expression inhibits prostate cancer cell migration , 2003, Oncogene.

[15]  Christian A. Rees,et al.  Systematic variation in gene expression patterns in human cancer cell lines , 2000, Nature Genetics.

[16]  H. Aburatani,et al.  Differential gene expression profiles of scirrhous gastric cancer cells with high metastatic potential to peritoneum or lymph nodes. , 2001, Cancer research.

[17]  Sei-Hyun Ahn,et al.  Differential expression of annexin I in human mammary ductal epithelial cells in normal and benign and malignant breast tissues , 1997, Clinical & Experimental Metastasis.

[18]  J. Ferlay,et al.  Head and neck cancer: a global perspective on epidemiology and prognosis. , 1998, Anticancer research.

[19]  M. Hollingsworth,et al.  Enhanced expression of annexin II in human pancreatic carcinoma cells and primary pancreatic cancers. , 1993, Carcinogenesis.

[20]  A. Hanby,et al.  Annexin VI has tumour-suppressor activity in human A431 squamous epithelial carcinoma cells. , 1995, British Journal of Cancer.

[21]  S. Kamel‐Reid,et al.  Molecular cytogenetic analysis of head and neck squamous cell carcinoma: By comparative genomic hybridization, spectral karyotyping, and expression array analysis , 2002, Head & neck.

[22]  S. Moss,et al.  Annexins: from structure to function. , 2002, Physiological reviews.

[23]  Nan Hu,et al.  2D Differential In-gel Electrophoresis for the Identification of Esophageal Scans Cell Cancer-specific Protein Markers* , 2002, Molecular & Cellular Proteomics.

[24]  Wei Xin,et al.  Dysregulation of the annexin family protein family is associated with prostate cancer progression. , 2003, The American journal of pathology.

[25]  David I. Smith,et al.  Identification of underexpressed genes in early- and late-stage primary ovarian tumors by suppression subtraction hybridization. , 2002, Cancer research.

[26]  R. Flower,et al.  Human annexin 1 is highly expressed during the differentiation of the epithelial cell line A 549: involvement of nuclear factor interleukin 6 in phorbol ester induction of annexin 1. , 1998, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[27]  D. Gilroy,et al.  Attenuation of glucocorticoid functions in an Anx-A1-/- cell line. , 2003, The Biochemical journal.

[28]  S. Violette,et al.  Role of lipocortin I in the glucocorticoid induction of the terminal differentiation of a human squamous carcinoma , 1990, Journal of cellular physiology.

[29]  M. P. Fernández,et al.  A BC200-derived element and Z-DNA as structural markers in annexin I genes: Relevance to Alu evolution and annexin tetrad formation , 1995, Journal of Molecular Evolution.

[30]  D. Ornstein,et al.  Dysregulation of annexin I protein expression in high-grade prostatic intraepithelial neoplasia and prostate cancer. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[31]  P R Taylor,et al.  Loss of annexin 1 correlates with early onset of tumorigenesis in esophageal and prostate carcinoma. , 2000, Cancer research.

[32]  J. Rand,et al.  The annexinopathies: a new category of diseases. , 2000, Biochimica et biophysica acta.

[33]  N. Collins,et al.  Modulation of paclitaxel resistance by annexin IV in human cancer cell lines , 2000, British Journal of Cancer.

[34]  M. Ohnishi,et al.  Enhanced expression of the protein kinase substrate annexin in human hepatocellular carcinoma. , 1996, Hepatology.

[35]  T. Kręcicki,et al.  Epidermal growth factor receptor (EGFR), proliferating cell nuclear antigen (PCNA) and Ki-67 antigen in laryngeal epithelial lesions. , 1999, Oral oncology.

[36]  Y. Jeng,et al.  Down-regulation of annexin A10 in hepatocellular carcinoma is associated with vascular invasion, early recurrence, and poor prognosis in synergy with p53 mutation. , 2002, The American journal of pathology.

[37]  M. Esteller.  CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future , 2002, Oncogene.