Fluorescence in situ hybridization markers for prediction of cervical lymph node metastases

Am J Pathol. 2009 Dec;175(6):2637-45. doi: 10.2353/ajpath.2009.090289. Epub 2009 Nov 5.

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / biosynthesis
  • AMP-Activated Protein Kinases / genetics
  • Adult
  • Aged
  • Biomarkers, Tumor / genetics*
  • Cyclin D1 / biosynthesis
  • Cyclin D1 / genetics
  • Female
  • Homeodomain Proteins / biosynthesis
  • Homeodomain Proteins / genetics
  • Humans
  • In Situ Hybridization, Fluorescence*
  • Lymphatic Metastasis / pathology*
  • Lysosomal Membrane Proteins / biosynthesis
  • Lysosomal Membrane Proteins / genetics
  • Middle Aged
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Staging
  • ROC Curve
  • Sensitivity and Specificity
  • Tumor Suppressor Proteins / biosynthesis
  • Tumor Suppressor Proteins / genetics
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • CCND1 protein, human
  • Homeodomain Proteins
  • LAMP3 protein, human
  • Lysosomal Membrane Proteins
  • Neoplasm Proteins
  • Tumor Suppressor Proteins
  • prospero-related homeobox 1 protein
  • Cyclin D1
  • AMP-Activated Protein Kinases
  • PRKAA1 protein, human