title: The relationship between semaphorin 3C and microvessel density in the progression of breast and oral neoplasia.
abstract: This study aimed to identify the expression of semaphorin 3C (SEMA3C) in the normal-metastatic spectrum of breast and oral cancers, and correlate expression with microvessel density (MVD, CD31), a surrogate marker of angiogenesis. Histological analysis revealed that SEMA3C expression was reduced in the development of oral cancer from normal oral tissue (P<0.0001) and expression was inversely correlated with MVD (r=-0.394, P=0.05). In contrast, SEMA3C expression increased in the transition from normal to invasive breast disease in epithelial/tumour cells (P=0.001) and endothelial cells (P=0.006), with both correlating weakly with MVD (r=0.35, p=0.03 and r=0.243, p=0.041 respectively). Furthermore, histological analysis of a breast cancer tissue microarray revealed a weak positive correlation with tumour grade (r=0.305, P=<0.001) and biological phenotype (r=0.237, p=0.004) with tumour cell expression of SEMA3C highest in triple negative and ER-, PR-, HER2+ subtypes. These data suggest that SEMA3C expression is differentially regulated in the development and progression of breast versus oral neoplasia, and that increased expression of SEMA3C may be modulating breast cancer progression and angiogenesis, and could represent a biomarker of metastatic disease.
authors.affiliation: Microcirculation Research Group, Academic Unit of Surgical Oncology, The Medical School, Faculty of Medicine, Dentistry & Health, University of Sheffield, Sheffield S10 2RX, UK.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Cole-Healy
authors.affiliation: Academic Unit of Pathology, The Medical School, Faculty of Medicine, Dentistry & Health, University of Sheffield, Sheffield S10 2RX, UK.
authors.forename: Patricia
authors.initials: P
authors.lastname: Vergani
authors.affiliation: Academic Unit of Oral & Maxillofacial Pathology, School of Clinical Dentistry Faculty of Medicine, Dentistry & Health, University of Sheffield, Sheffield S10 2TA, UK.
authors.forename: Keith
authors.initials: K
authors.lastname: Hunter
authors.affiliation: Microcirculation Research Group, Academic Unit of Surgical Oncology, The Medical School, Faculty of Medicine, Dentistry & Health, University of Sheffield, Sheffield S10 2RX, UK.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Brown
authors.affiliation: Microcirculation Research Group, Academic Unit of Surgical Oncology, The Medical School, Faculty of Medicine, Dentistry & Health, University of Sheffield, Sheffield S10 2RX, UK.
authors.forename: Malcolm W R
authors.initials: MW
authors.lastname: Reed
authors.affiliation: Microcirculation Research Group, Academic Unit of Surgical Oncology, The Medical School, Faculty of Medicine, Dentistry & Health, University of Sheffield, Sheffield S10 2RX, UK. Electronic address: c.a.staton@shef.ac.uk.
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Staton
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D055806:Microvessels / Q000473:pathology; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics*; D011379:Prognosis; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C543908:Sema3C protein, human; D039961:Semaphorins
keywords: Angiogenesis; Breast cancer; Class 3 semaphorin; SEMA3C; Squamous cell carcinoma