Review Article Molecular pathology and potential therapeutic targets in esophageal basaloid squamous cell carcinoma

Basaloid squamous cell carcinoma (BSCC) is a rare and poorly differentiated variant of typical squamous cell carcinoma. Emerging studies show that genetic alterations are more frequent in BSCC than in conventional SCC, and some of which led to the identification of potential therapeutic targets in esophageal BSCC. Approximately half of the esophageal BSCC cases harbor either an EGFR mutation or amplification, and these occur in a mutually exclu - sive fashion. Therefore, the application of tyrosine kinase inhibitors may be beneficial to esophageal BSCC patients. This tumor is partly characterized by the activation of the Wnt and Hedgehog (HH) signaling pathways. Wnt signaling is activated by SFRP2 promoter hypermethylation and HH signaling is activated by the frequent mutations in PTCH1. Increasing evidence shows that the Wnt signaling pathway is involved in cross-talk with other developmental path- ways, including the HH pathway. Therefore, pharmaceutical therapy targeting both the HH and Wnt pathways would be quite effective in patients with esophageal BSCC with highly malignant potential. In this review, we discuss the pathology, prognostic factors, genetic alterations and potential therapeutic targets in BSCC of esophagus.

[1]  B. Druker,et al.  Crosstalk between KIT and FGFR3 Promotes Gastrointestinal Stromal Tumor Cell Growth and Drug Resistance. , 2015, Cancer research.

[2]  Y. Kajiyama,et al.  PTCH1 mutation is a frequent event in oesophageal basaloid squamous cell carcinoma. , 2015, Mutagenesis.

[3]  Min Goo Lee,et al.  Phase II Clinical and Exploratory Biomarker Study of Dacomitinib in Patients with Recurrent and/or Metastatic Squamous Cell Carcinoma of Head and Neck , 2014, Clinical Cancer Research.

[4]  M. Rubin,et al.  MYB-NFIB gene fusion in adenoid cystic carcinoma of the breast with special focus paid to the solid variant with basaloid features. , 2014, Human pathology.

[5]  P. Hainaut,et al.  Lung Squamous Cell Carcinomas with Basaloid Histology Represent a Specific Molecular Entity , 2014, Clinical Cancer Research.

[6]  Y. Kajiyama,et al.  Downregulation of sFRP-2 by epigenetic silencing activates the β-catenin/Wnt signaling pathway in esophageal basaloid squamous cell carcinoma , 2014, Virchows Archiv.

[7]  D. Schadendorf,et al.  TERT Promoter Mutations in Familial and Sporadic Melanoma , 2013, Science.

[8]  Lynda Chin,et al.  Highly Recurrent TERT Promoter Mutations in Human Melanoma , 2013, Science.

[9]  Y. Kajiyama,et al.  Immunohistochemical and oncogenetic analyses of the esophageal basaloid squamous cell carcinoma in comparison with conventional squamous cell carcinomas. , 2012, Human pathology.

[10]  R. Korn,et al.  Metastatic basal cell carcinoma in the era of hedgehog signaling pathway inhibitors , 2012, Cancer.

[11]  Kris Chang,et al.  Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. , 2012, The New England journal of medicine.

[12]  Wei Zhang,et al.  Frizzled7 as an emerging target for cancer therapy. , 2012, Cellular signalling.

[13]  K. Geissler,et al.  Pathways involved in Drosophila and human cancer development: the Notch, Hedgehog, Wingless, Runt, and Trithorax pathway , 2012, Annals of Hematology.

[14]  Di-tian Liu,et al.  Basaloid squamous cell carcinoma of the esophagus , 2012, Journal of Cancer Research and Clinical Oncology.

[15]  Hua-Qing Wang,et al.  Frizzled-8 as a putative therapeutic target in human lung cancer. , 2012, Biochemical and biophysical research communications.

[16]  K. Hankenson,et al.  Integration of BMP, Wnt, and notch signaling pathways in osteoblast differentiation , 2011, Journal of cellular biochemistry.

[17]  P. Jänne,et al.  Activation of ERBB2 Signaling Causes Resistance to the EGFR-Directed Therapeutic Antibody Cetuximab , 2011, Science Translational Medicine.

[18]  C. Moskaluk,et al.  Analysis of MYB expression and MYB-NFIB gene fusions in adenoid cystic carcinoma and other salivary neoplasms , 2011, Modern Pathology.

[19]  P. Schofield,et al.  Hedgehog overexpression is associated with stromal interactions and predicts for poor outcome in breast cancer. , 2011, Cancer research.

[20]  T. Conroy,et al.  Phase II randomised trial of chemoradiotherapy with FOLFOX4 or cisplatin plus fluorouracil in oesophageal cancer , 2010, British Journal of Cancer.

[21]  D. V. Von Hoff,et al.  Hunting the Hedgehog Pathway , 2010, Clinical pharmacology and therapeutics.

[22]  Jie Hyun Kim,et al.  Contrasting activity of Hedgehog and Wnt pathways according to gastric cancer cell differentiation: Relevance of crosstalk mechanisms , 2010, Cancer science.

[23]  H. Horlings,et al.  Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck , 2009, Proceedings of the National Academy of Sciences.

[24]  David R. Jones,et al.  Basaloid Squamous Cell Carcinoma of the Esophagus: Assessment for High-risk Human Papillomavirus and Related Molecular Markers , 2009, The American journal of surgical pathology.

[25]  S. Xiao,et al.  Basaloid squamous cell carcinoma of the esophagus with or without adenoid cystic features. , 2009, Archives of pathology & laboratory medicine.

[26]  E. Epstein Basal cell carcinomas: attack of the hedgehog , 2008, Nature Reviews Cancer.

[27]  W. Westra,et al.  Basaloid Squamous Cell Carcinoma of the Head and Neck is a Mixed Variant That Can be Further Resolved by HPV Status , 2008, The American journal of surgical pathology.

[28]  A. Maitra,et al.  Targeted inhibition of hedgehog signaling by cyclopamine prodrugs for advanced prostate cancer. , 2008, Bioorganic & medicinal chemistry.

[29]  Yusuke Nakamura,et al.  Radioimmunotherapy of human synovial sarcoma using a monoclonal antibody against FZD10 , 2008, Cancer science.

[30]  S. Takada,et al.  Wnt canonical pathway restricts graded Shh/Gli patterning activity through the regulation of Gli3 expression , 2007, Development.

[31]  S. Patil,et al.  Human papillomavirus (HPV)-related oropharyngeal nonkeratinizing squamous cell carcinoma: characterization of a distinct phenotype. , 2006, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[32]  Maria Kasper,et al.  GLI transcription factors: mediators of oncogenic Hedgehog signalling. , 2006, European journal of cancer.

[33]  F. Watt Unexpected Hedgehog-Wnt interactions in epithelial differentiation. , 2004, Trends in molecular medicine.

[34]  Lawrence Lum,et al.  The Hedgehog Response Network: Sensors, Switches, and Routers , 2004, Science.

[35]  William Gaffield,et al.  Indian Hedgehog is an antagonist of Wnt signaling in colonic epithelial cell differentiation , 2004, Nature Genetics.

[36]  J. Taipale,et al.  Hedgehog-Mediated Patterning of the Mammalian Embryo Requires Transporter-like Function of Dispatched , 2002, Cell.

[37]  J. Wong,et al.  Oesophageal basaloid squamous cell carcinoma: a unique clinicopathological entity with telomerase activity as a prognostic indicator , 2001, The Journal of pathology.

[38]  T. Owonikoko,et al.  Comparative analysis of basaloid and typical squamous cell carcinoma of the oesophagus: a molecular biological and immunohistochemical study , 2001, The Journal of pathology.

[39]  Jang,et al.  Basaloid squamous carcinoma of the oesophagus: a distinct neoplasm with multipotential differentiation , 2000, Histopathology.

[40]  M. Wolter,et al.  Expression of Bcl-2 and amplification of c-myc are frequent in basaloid squamous cell carcinomas of the esophagus. , 1999, The American journal of pathology.

[41]  P. Beachy,et al.  Teratogen-mediated inhibition of target tissue response to Shh signaling. , 1998, Science.

[42]  W. Morice,et al.  Distinction of basaloid squamous cell carcinoma from adenoid cystic and small cell undifferentiated carcinoma by immunohistochemistry. , 1998, Human pathology.

[43]  R. Willers,et al.  Basaloid squamous cell carcinoma of the esophagus , 1997, Cancer.

[44]  C. James,et al.  Sporadic medulloblastomas contain PTCH mutations. , 1997, Cancer research.

[45]  R. Vollmer,et al.  Basaloid-squamous carcinoma of the tongue, hypopharynx, and larynx: report of 10 cases. , 1986, Human pathology.

[46]  K. Momma,et al.  Superficial basaloid squamous carcinoma of the esophagus. A clinicopathological and immunohistochemical study of 12 cases. , 2003, Pathology, research and practice.