p53, cellular proliferation, and apoptosis-related factors in thymic neuroendocrine tumors.
Thymic neuroendocrine tumors are biologically aggressive neoplasms with extensive local invasion and high mortality. Although various markers of cellular proliferation and apoptosis have correlated with degrees of tumor differentiation in pulmonary neuroendocrine neoplasms, they have not been systematically studied in thymic neuroendocrine tumors. We immunostained 21 cases of thymic neuroendocrine tumors for p53, MIB-1, and the apoptosis-related markers Bcl-2, Bcl-x, and Bax. By histological classification the cases were low-grade (nine cases), intermediate-grade (eight cases), and high-grade (four cases) thymic neuroendocrine tumors. p53 was expressed in five cases: 1/9 low grade, 3/8 intermediate grade, and 2/4 high grade. The mean cellular proliferation (MIB-1) was 7.1% (range 2-12%) in low-grade thymic neuroendocrine tumors, 6.1% (range 2-15%) in intermediate-grade thymic neuroendocrine tumors, and 34.2% (range 2-80%) in high-grade thymic neuroendocrine tumors. Bcl-2 was expressed in 16 cases: 7/9 low grade, 5/8 intermediate grade, and 4/4 high grade. Bcl-x was expressed in 16 cases: 7/9 low grade, 6/8 intermediate grade, and 3/4 high grade. Bax was expressed in 13 cases: 5/9 low grade, 4/8 intermediate grade, and 4/4 high grade. The presence of mutant p53 in the tumor was associated with a statistically significant decreased mean survival (P<0.05). In contrast, either by positive or negative staining or by the score technique (staining intensity x percentage of cells staining), the presence of Bcl-x was associated with an increased mean survival (P<0.05). Finally, a Bcl-x : Bax ratio >or=1 was also associated with an increased mean survival, as compared to a Bcl-x : Bax ratio >or=1 (P<0.05). Our study shows that p53 expression and certain apoptosis markers correlate with survival. The expression of these markers may account for differences in biological behavior.
Gal
Anthony A
AA
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. agal@emory.edu
Sheppard
Mary N
MN
Nolen
John D L
JD
Cohen
Cynthia
C
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000032:analysis*; D049109:Cell Proliferation; D005500:Follow-Up Studies; D005845:Georgia; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis*; D008131:London; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000737:chemistry* / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016017:Odds Ratio; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D018570:Risk Assessment; D013953:Thymus Neoplasms / Q000737:chemistry* / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy; D013997:Time Factors; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D051028:bcl-2-Associated X Protein / Q000032:analysis; D051020:bcl-X Protein / Q000032:analysis
D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein