Immunoglobulin G Expression and Its Colocalization With Complement Proteins in Papillary Thyroid Cancer

Mod Pathol. 2012 Jan;25(1):36-45. doi: 10.1038/modpathol.2011.139. Epub 2011 Sep 9.

Abstract

Except for the well-known immunoglobulin G (IgG) producing cell types, ie, mature B lymphocytes and plasma cells, various non-lymphoid cell types, including human cancer cells, neurons, and some specified epithelial cells, have been found to express IgG. In this study, we detected the expression of the heavy chain of IgG (IgGγ) and kappa light chain (Igκ) in papillary thyroid cancer cells. Using in situ hybridization, we detected the constant region of human IgG1 (IGHG1) in papillary thyroid cancer cells. With laser capture microdissection followed by RT-PCR, mRNA transcripts of IGHG1, Igκ, recombination activating gene 1 (RAG1), RAG2, and activation-induced cytidine deaminase genes were successfully amplified from isolated papillary thyroid cancer cells. We further confirmed IgG protein expression with immunohistochemistry and found that none of the IgG receptors was expressed in papillary thyroid cancer. Differences in the level of IgGγ expression between tumor size, between papillary thyroid cancer and normal thyroid tissue, as well as between papillary thyroid cancer with and without lymph node metastasis were significant. Taken together, these results indicate that IgG is produced by papillary thyroid cancer cells and that it might be positively related to the growth and metastasis of papillary thyroid cancer cells. Furthermore, it was demonstrated that IgGγ colocalized with complement proteins in the same cancer cells, which could indicate that immune complexes were formed. Such immune complexes might consist of IgG synthesized by the host against tumor surface antigens and locally produced anti-idiotypic IgG with specificity for the variable region of these 'primary' antibodies. The cancer cells might thus escape the host tumor-antigen-specific immune responses, hence promoting tumor progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Biopsy
  • Carcinoma
  • Carcinoma, Papillary
  • Complement System Proteins / analysis*
  • Complement System Proteins / genetics
  • Cytidine Deaminase / genetics
  • DNA-Binding Proteins / genetics
  • Female
  • Homeodomain Proteins / genetics
  • Humans
  • Immunoglobulin G / analysis*
  • Immunoglobulin G / genetics
  • Immunoglobulin gamma-Chains / analysis*
  • Immunoglobulin gamma-Chains / genetics
  • Immunoglobulin kappa-Chains / analysis*
  • Immunoglobulin kappa-Chains / genetics
  • Immunohistochemistry
  • In Situ Hybridization
  • Laser Capture Microdissection
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / immunology*
  • Thyroid Neoplasms / pathology
  • Tissue Array Analysis

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Immunoglobulin G
  • Immunoglobulin gamma-Chains
  • Immunoglobulin kappa-Chains
  • Nuclear Proteins
  • RAG2 protein, human
  • RNA, Messenger
  • RAG-1 protein
  • Complement System Proteins
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase