Survivin, bcl-2, bax, and bcl-X gene expression in sentinel lymph nodes from melanoma patients

J Clin Oncol. 2003 Jan 15;21(2):306-12. doi: 10.1200/JCO.2003.08.066.

Abstract

Purpose: The expression of apoptosis-related genes, such as survivin, bcl-2, bcl-X, and bax, has been evaluated by reverse transcriptase polymerase chain reaction (RT-PCR) and by immunohistochemistry in sentinel lymph nodes (SLNs) from melanoma patients and then correlated to the outcome of patients.

Patients and methods: Thirty-six SLNs were examined. After RNA extraction, an RT-PCR followed by Southern blot hybridization was performed to detect survivin, bcl-2, bcl-X, and bax mRNA. bcl-2, survivin, and bax gene expression was evaluated, whenever possible, also by immunohistochemistry at the protein level.

Results: We found a significant correlation (P <.005) between survivin expression and outcome of patients; in fact, 61.5% of patients expressing survivin gene progressed or died because of the disease, whereas 38.5% are currently disease-free. Among patients negative for survivin expression, 100% are disease-free after a median follow-up time of 52.9 months. We did not find a significant correlation between bcl-2, bax, and bcl-X gene expression and outcome of patients. In fact, these genes were found equally expressed in patients with disease progression and in disease-free patients.

Conclusion: Our findings show a variable expression of apoptosis-related genes in SLNs of melanoma patients; more interestingly, we found that survivin expression correlates to outcome of patients in a statistically significant way, whereas the expression of other genes, such as bcl-2, bax, and bcl-X, did not seem to correlate to progression of disease. We suggest that the detection of survivin gene expression by RT-PCR in SLNs may be a useful prognostic indicator.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / metabolism
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • DNA Primers / chemistry
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoenzyme Techniques
  • Inhibitor of Apoptosis Proteins
  • Lymph Nodes / metabolism*
  • Male
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Middle Aged
  • Neoplasm Proteins
  • Prognosis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sentinel Lymph Node Biopsy / methods
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • Survivin
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-2-Associated X Protein
  • bcl-X Protein

Substances

  • Antigens, Neoplasm
  • BAX protein, human
  • BCL2L1 protein, human
  • BIRC5 protein, human
  • Biomarkers, Tumor
  • DNA Primers
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • RNA, Neoplasm
  • Survivin
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • bcl-X Protein