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


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.


CONCLUSIONS
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.
Gradilone
Angela
A
Department of Experimental Medicine and Pathology, University of Rome La Sapienza, Rome, Italy.
Gazzaniga
Paola
P
Ribuffo
Diego
D
Scarpa
Susanna
S
Cigna
Emanuele
E
Vasaturo
Fortunata
F
Bottoni
Ugo
U
Innocenzi
Daniele
D
Calvieri
Stefano
S
Scuderi
Nicolo'
N
Frati
Luigi
L
Aglianò
Anna Maria
AM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D051034:Inhibitor of Apoptosis Proteins; D008198:Lymph Nodes / Q000378:metabolism*; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D021701:Sentinel Lymph Node Biopsy / Q000379:methods; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D000951:Antigens, Neoplasm; C494826:BAX protein, human; C494811:BCL2L1 protein, human; C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D017931:DNA Primers; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein