title: Fluorescence in situ hybridization markers for prediction of cervical lymph node metastases.
abstract: The presence of lymph node metastases is associated with poor prognosis in early stage cervical cancer. As of yet, no molecular markers predicting lymph node metastases have been identified. We examined single genetic markers and a composite marker, comprised of three fluorescence in situ hybridization (FISH) probes targeting the genes LAMP3, PROX1, and PRKAA1, in pretreatment cervical biopsies from 16 lymph node positive cases and 15 lymph node negative controls from women with stage IB and IIA cervical cancer. In addition, we determined clonal patterns by including CCND1 to compare the clonal constitution of primary tumors and associated lymph node metastases. The composite FISH marker allowed for classification of patients into those with and without lymph node metastases with a sensitivity and specificity of 75% and 87%, respectively (P = 0.001). The positive predictive value and negative predictive value were 86% and 76%, respectively. Clonal patterns varied among the tumors. In many cases, changes between the primary tumor and lymph node metastases in the most common clones may indicate that certain clones have a growth advantage for establishing metastases in lymph nodes. We conclude that the composite FISH marker may be useful for determining risk for subsequent development of lymph node metastases in patients with cervical cancer.
authors.affiliation: Department of Oncology-Pathology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Darawalee
authors.initials: D
authors.lastname: Wangsa
authors.forename: Kerstin
authors.initials: K
authors.lastname: Heselmeyer-Haddad
authors.forename: Patricia
authors.initials: P
authors.lastname: Ried
authors.forename: Elina
authors.initials: E
authors.lastname: Eriksson
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Schäffer
authors.forename: Larry E
authors.initials: LE
authors.lastname: Morrison
authors.forename: Juhua
authors.initials: J
authors.lastname: Luo
authors.forename: Gert
authors.initials: G
authors.lastname: Auer
authors.forename: Eva
authors.initials: E
authors.lastname: Munck-Wikland
authors.forename: Thomas
authors.initials: T
authors.lastname: Ried
authors.forename: Elisabeth Avall
authors.initials: EA
authors.lastname: Lundqvist
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000096:biosynthesis / Q000235:genetics; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis / Q000473:pathology*; D051907:Lysosomal Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009367:Neoplasm Staging; D012372:ROC Curve; D012680:Sensitivity and Specificity; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology*; D000098551:Prospero-Related Homeobox 1 Protein; D059666:Lysosomal-Associated Membrane Protein 3
chemical_list: D055372:AMP-Activated Protein Kinases; D014408:Biomarkers, Tumor; D019938:Cyclin D1; D018398:Homeodomain Proteins; D051907:Lysosomal Membrane Proteins; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; C530104:CCND1 protein, human; C114233:LAMP3 protein, human; D059666:Lysosomal-Associated Membrane Protein 3; C526180:PRKAA1 protein, human