Expression of Bcl-2 family proteins in advanced laryngeal squamous cell carcinoma: correlation with response to chemotherapy and organ preservation.
OBJECTIVE
Induction chemotherapy and definitive radiation therapy in advanced laryngeal cancer has been shown to achieve survival rates that are similar to total laryngectomy and postoperative radiation therapy. In patients with advanced laryngeal cancer, quality of life can be significantly enhanced by treatment regimens that preserve the larynx. However, which patients will respond best to organ preservation protocols remains unknown. The Bcl-2 family proteins are involved in control of apoptosis and, potentially, tumor response to chemotherapy.


METHODS
Retrospective analysis of immunohistochemical tumor characteristics and clinical outcome.


METHODS
To determine whether Bcl-2 family proteins were predictive of successful organ preservation, immunohistochemical analysis of tissue specimens from 47 patients with advanced laryngeal cancer from the U.S. Department of Veterans Affairs Cooperative Study Program (VA CSP-268) were evaluated for the expression of Bcl-2, Bcl-X(L), and Bax protein expression. Tumor response was classified as either complete or partial/nonresponse after induction chemotherapy. Protein expression was correlated with tumor response, organ preservation, and overall patient survival.


RESULTS
The Bcl-2 protein was expressed at high levels in only 15% of specimens, but five of seven tumors with high Bcl-2 showed complete response (P = .10). The majority of tumors expressed high levels of Bcl-X(L) (74%). Reduced expression of Bcl-X(L) was associated with a complete response (P = .143) and with larynx preservation (P = .06). Most patients (81%) had increased levels of Bax expression. Reduced expression of Bax was associated with a complete response rate (P = .074), but there was no correlation between Bax expression and larynx preservation.


CONCLUSIONS
The findings indicate that laryngeal cancer cells typically produce high levels of only one of the apoptosis protective proteins, Bcl-2 or Bcl-X(L). Prospective studies of larger numbers of patients are under way to determine whether Bcl-X(L) expression will be a useful marker predicting larynx preservation.
Trask
Douglas K
DK
Department of Otolaryngology-Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, USA.
Wolf
Gregory T
GT
Bradford
Carol R
CR
Fisher
Susan G
SG
Devaney
Kenneth
K
Johnson
Mark
M
Singleton
Timothy
T
Wicha
Max
M
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage; D015331:Cohort Studies; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D002945:Cisplatin; D005472:Fluorouracil