Expression of Bcl-2 in gastrointestinal stromal tumors

Correlation with progression-free survival in 81 patients treated with imatinib mesylate

Dejka M. Steinert, Mauricio Oyarzo, Xuemei Wang, Haesun Choi, Peter F. Thall, L. Jeffrey Medeiros, A. Kevin Raymond, Robert S. Benjamin, Wei Zhang, Jonathan Trent

Research output: Contribution to journalArticle

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Abstract

BACKGROUND. The natural history of gastrointestinal stromal tumor (GIST) has been revolutionized by imatinib mesylate (imatinib) therapy. Before imatinib, Bcl-2 expression in GIST was associated with a worse prognosis or added no additional prognostic value. To the authors' knowledge, the current study is the first to evaluate Bcl-2 expression in pre-imatinib GIST tissue samples as a prognostic marker of progression-free survival (PFS) time in patients treated with imatinib. METHODS. The cases of 81 patients with GIST who were evaluated between December 15, 2000 and September 1, 2001 were retrospectively reviewed. Clinicopathologic variables were reviewed. GIST cell morphology and patterns of Bcl-2 expression were described. The methods of Kaplan-Meier and the Cox proportional hazards regression model were used for statistical analysis. RESULTS. Sixty-one (75%) patients had tumors that expressed Bcl-2, and 20 (25%) patients had tumors that were negative for Bcl-2. All epithelioid tumors (n = 12) expressed Bcl-2 and tumors with mixed morphology exhibited Bcl-2 expression in the epithelioid component. A trend toward longer PFS for patients whose tumors expressed Bcl-2 at a greater immunohistochemical intensity was observed (20.6 mos for no Bcl-2 expression; 28.3 mos for 1++Bcl-2 expression; 31.9 mos for 1.5++Bcl-2 expression; 40.8 mos for 2++Bcl-2 expresssion; and 35.9 mos for 3++Bcl-2 expression). CONCLUSIONS. In contrast to studies performed in the preimatinib era, in which Bcl-2 was found to be a negative prognostic indicator, the current study suggests a trend toward better PFS with increasing Bcl-2 expression level in GISTs from patients subsequently treated with imatinib. Larger studies may help elucidate the influence of Bcl-2 expression on PFS after therapy with imatinib.

Original languageEnglish
Pages (from-to)1617-1623
Number of pages7
JournalCancer
Volume106
Issue number7
DOIs
StatePublished - Apr 1 2006
Externally publishedYes

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Gastrointestinal Stromal Tumors
Disease-Free Survival
Neoplasms
Stromal Cells
Imatinib Mesylate
Proportional Hazards Models
Therapeutics

Keywords

  • Apoptosis
  • Clinicopathologic
  • Gastrointestinal stromal tumor (GIST)
  • Sarcoma
  • Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Steinert, D. M., Oyarzo, M., Wang, X., Choi, H., Thall, P. F., Medeiros, L. J., ... Trent, J. (2006). Expression of Bcl-2 in gastrointestinal stromal tumors: Correlation with progression-free survival in 81 patients treated with imatinib mesylate. Cancer, 106(7), 1617-1623. https://doi.org/10.1002/cncr.21781

Expression of Bcl-2 in gastrointestinal stromal tumors : Correlation with progression-free survival in 81 patients treated with imatinib mesylate. / Steinert, Dejka M.; Oyarzo, Mauricio; Wang, Xuemei; Choi, Haesun; Thall, Peter F.; Medeiros, L. Jeffrey; Raymond, A. Kevin; Benjamin, Robert S.; Zhang, Wei; Trent, Jonathan.

In: Cancer, Vol. 106, No. 7, 01.04.2006, p. 1617-1623.

Research output: Contribution to journalArticle

Steinert, DM, Oyarzo, M, Wang, X, Choi, H, Thall, PF, Medeiros, LJ, Raymond, AK, Benjamin, RS, Zhang, W & Trent, J 2006, 'Expression of Bcl-2 in gastrointestinal stromal tumors: Correlation with progression-free survival in 81 patients treated with imatinib mesylate', Cancer, vol. 106, no. 7, pp. 1617-1623. https://doi.org/10.1002/cncr.21781
Steinert, Dejka M. ; Oyarzo, Mauricio ; Wang, Xuemei ; Choi, Haesun ; Thall, Peter F. ; Medeiros, L. Jeffrey ; Raymond, A. Kevin ; Benjamin, Robert S. ; Zhang, Wei ; Trent, Jonathan. / Expression of Bcl-2 in gastrointestinal stromal tumors : Correlation with progression-free survival in 81 patients treated with imatinib mesylate. In: Cancer. 2006 ; Vol. 106, No. 7. pp. 1617-1623.
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abstract = "BACKGROUND. The natural history of gastrointestinal stromal tumor (GIST) has been revolutionized by imatinib mesylate (imatinib) therapy. Before imatinib, Bcl-2 expression in GIST was associated with a worse prognosis or added no additional prognostic value. To the authors' knowledge, the current study is the first to evaluate Bcl-2 expression in pre-imatinib GIST tissue samples as a prognostic marker of progression-free survival (PFS) time in patients treated with imatinib. METHODS. The cases of 81 patients with GIST who were evaluated between December 15, 2000 and September 1, 2001 were retrospectively reviewed. Clinicopathologic variables were reviewed. GIST cell morphology and patterns of Bcl-2 expression were described. The methods of Kaplan-Meier and the Cox proportional hazards regression model were used for statistical analysis. RESULTS. Sixty-one (75{\%}) patients had tumors that expressed Bcl-2, and 20 (25{\%}) patients had tumors that were negative for Bcl-2. All epithelioid tumors (n = 12) expressed Bcl-2 and tumors with mixed morphology exhibited Bcl-2 expression in the epithelioid component. A trend toward longer PFS for patients whose tumors expressed Bcl-2 at a greater immunohistochemical intensity was observed (20.6 mos for no Bcl-2 expression; 28.3 mos for 1++Bcl-2 expression; 31.9 mos for 1.5++Bcl-2 expression; 40.8 mos for 2++Bcl-2 expresssion; and 35.9 mos for 3++Bcl-2 expression). CONCLUSIONS. In contrast to studies performed in the preimatinib era, in which Bcl-2 was found to be a negative prognostic indicator, the current study suggests a trend toward better PFS with increasing Bcl-2 expression level in GISTs from patients subsequently treated with imatinib. Larger studies may help elucidate the influence of Bcl-2 expression on PFS after therapy with imatinib.",
keywords = "Apoptosis, Clinicopathologic, Gastrointestinal stromal tumor (GIST), Sarcoma, Survival",
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T2 - Correlation with progression-free survival in 81 patients treated with imatinib mesylate

AU - Steinert, Dejka M.

AU - Oyarzo, Mauricio

AU - Wang, Xuemei

AU - Choi, Haesun

AU - Thall, Peter F.

AU - Medeiros, L. Jeffrey

AU - Raymond, A. Kevin

AU - Benjamin, Robert S.

AU - Zhang, Wei

AU - Trent, Jonathan

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N2 - BACKGROUND. The natural history of gastrointestinal stromal tumor (GIST) has been revolutionized by imatinib mesylate (imatinib) therapy. Before imatinib, Bcl-2 expression in GIST was associated with a worse prognosis or added no additional prognostic value. To the authors' knowledge, the current study is the first to evaluate Bcl-2 expression in pre-imatinib GIST tissue samples as a prognostic marker of progression-free survival (PFS) time in patients treated with imatinib. METHODS. The cases of 81 patients with GIST who were evaluated between December 15, 2000 and September 1, 2001 were retrospectively reviewed. Clinicopathologic variables were reviewed. GIST cell morphology and patterns of Bcl-2 expression were described. The methods of Kaplan-Meier and the Cox proportional hazards regression model were used for statistical analysis. RESULTS. Sixty-one (75%) patients had tumors that expressed Bcl-2, and 20 (25%) patients had tumors that were negative for Bcl-2. All epithelioid tumors (n = 12) expressed Bcl-2 and tumors with mixed morphology exhibited Bcl-2 expression in the epithelioid component. A trend toward longer PFS for patients whose tumors expressed Bcl-2 at a greater immunohistochemical intensity was observed (20.6 mos for no Bcl-2 expression; 28.3 mos for 1++Bcl-2 expression; 31.9 mos for 1.5++Bcl-2 expression; 40.8 mos for 2++Bcl-2 expresssion; and 35.9 mos for 3++Bcl-2 expression). CONCLUSIONS. In contrast to studies performed in the preimatinib era, in which Bcl-2 was found to be a negative prognostic indicator, the current study suggests a trend toward better PFS with increasing Bcl-2 expression level in GISTs from patients subsequently treated with imatinib. Larger studies may help elucidate the influence of Bcl-2 expression on PFS after therapy with imatinib.

AB - BACKGROUND. The natural history of gastrointestinal stromal tumor (GIST) has been revolutionized by imatinib mesylate (imatinib) therapy. Before imatinib, Bcl-2 expression in GIST was associated with a worse prognosis or added no additional prognostic value. To the authors' knowledge, the current study is the first to evaluate Bcl-2 expression in pre-imatinib GIST tissue samples as a prognostic marker of progression-free survival (PFS) time in patients treated with imatinib. METHODS. The cases of 81 patients with GIST who were evaluated between December 15, 2000 and September 1, 2001 were retrospectively reviewed. Clinicopathologic variables were reviewed. GIST cell morphology and patterns of Bcl-2 expression were described. The methods of Kaplan-Meier and the Cox proportional hazards regression model were used for statistical analysis. RESULTS. Sixty-one (75%) patients had tumors that expressed Bcl-2, and 20 (25%) patients had tumors that were negative for Bcl-2. All epithelioid tumors (n = 12) expressed Bcl-2 and tumors with mixed morphology exhibited Bcl-2 expression in the epithelioid component. A trend toward longer PFS for patients whose tumors expressed Bcl-2 at a greater immunohistochemical intensity was observed (20.6 mos for no Bcl-2 expression; 28.3 mos for 1++Bcl-2 expression; 31.9 mos for 1.5++Bcl-2 expression; 40.8 mos for 2++Bcl-2 expresssion; and 35.9 mos for 3++Bcl-2 expression). CONCLUSIONS. In contrast to studies performed in the preimatinib era, in which Bcl-2 was found to be a negative prognostic indicator, the current study suggests a trend toward better PFS with increasing Bcl-2 expression level in GISTs from patients subsequently treated with imatinib. Larger studies may help elucidate the influence of Bcl-2 expression on PFS after therapy with imatinib.

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KW - Gastrointestinal stromal tumor (GIST)

KW - Sarcoma

KW - Survival

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