Array-comparative genomic hybridization to detect genomewide changes in microdissected primary and metastatic oral squamous cell carcinomas

Mol Carcinog. 2006 Oct;45(10):721-31. doi: 10.1002/mc.20213.


Oral squamous cell carcinoma (OSCC) is a common worldwide malignancy. However, it is unclear what, if any, genomic alterations occur as the disease progresses to invasive and metastatic OSCC. This study used genomewide array-CGH in microdissected specimens to map genetic alterations found in primary OSCC and neck lymph node metastases. We used array-based comparative genomic hybridization (array-CGH) to screen genomewide alterations in eight pairs of microdissected tissue samples from primary and metastatic OSCC. In addition, 25 primary and metastatic OSCC tissue pairs were examined with immunohistochemistry for protein expression of the most frequently altered genes. The highest frequencies of gains were detected in LMYC, REL, TERC, PIK3CA, MYB, MDR1, HRAS, GARP, CCND2, FES, HER2, SIS, and SRY. The highest frequencies of losses were detected in p44S10, TIF1, LPL, MTAP, BMI1, EGR2, and MAP2K5. Genomic alterations in TGFbeta2, cellular retinoid-binding protein 1 gene (CRBP1), PIK3CA, HTR1B, HRAS, ERBB3, and STK6 differed significantly between primary OSCC and their metastatic counterparts. Genomic alterations in PRKCZ, ABL1, and FGF4 were significantly different in patients who died compared with those who survived. Immunohistochemistry confirmed high PIK3CA immunoreactivity in primary and metastatic OSCC. Higher FGF4 immunoreactivity in primary OSCC is associated with a worse prognosis. Loss of CRBP1 immunoreactivity is evident in primary and metastatic OSCC. Our study suggests that precise genomic profiling can be useful in determining gene number changes in OSCC. As our understanding of these changes grow, this profiling may become a practical tool for clinical evaluation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / secondary
  • Carcinoma, Squamous Cell / surgery
  • Female
  • Fibroblast Growth Factor 4 / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genome, Human / genetics*
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis / genetics*
  • Lymphatic Metastasis / pathology
  • Male
  • Microdissection
  • Middle Aged
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / pathology*
  • Mouth Neoplasms / secondary
  • Mouth Neoplasms / surgery
  • Nucleic Acid Probes / genetics
  • Oligonucleotide Array Sequence Analysis*
  • Survival Rate


  • FGF4 protein, human
  • Fibroblast Growth Factor 4
  • Nucleic Acid Probes