Radiation therapy induced changes in apoptosis and its major regulatory proteins, Bcl-2, Bcl-XL, and Bax, in locally advanced invasive squamous cell carcinoma of the cervix.
OBJECTIVE
Radiation therapy (RT) for cancer induces cell death by apoptosis. The major apoptotic regulatory molecules include Bcl-2, Bcl-XL (antiapoptotic), and Bax (proapoptotic) proteins. Invasive squamous cell carcinoma of the cervix is mainly treated by radiation, and hence our aim was to evaluate the changes induced by RT in the apoptotic index (AI) and to correlate this to the levels of the major pro- and antiapoptotic molecules.


METHODS
Paired biopsies were obtained in 30 cases of invasive carcinoma cervix before and after 10 Gy RT. The TUNEL assay was performed to detect apoptotic nuclei and Bcl-2, Bcl-XL, and Bax proteins detected by immunohistochemistry (IHC). Statistical analysis was performed using the Spearman rank correlation coefficient test.


RESULTS
Following RT, there was a significant increase in the mean AI [2.25 (+/-2.28) in post-RT vs 0.90 (+/-0.53) in the pre-RT group]. Bax, a major proapoptotic protein, was significantly increased following RT (P < 0.05), whereas the antiapoptotic Bcl-XL showed a significant decrease (P = 0.006). There was no significant change in Bcl-2 expression. The Bcl-2 and Bax IHC scores and the Bcl-2/Bax ratio did not correlate with AI in the 2 groups. There was an inverse correlation of Bcl-XL to AI in the pre-RT group (P = 0.003) but not in the post-RT group.


CONCLUSIONS
RT for invasive squamous cell carcinoma of cervix results in increased apoptotic cell death with the up-regulation of Bax, a proapoptotic protein, and the down-regulation of Bcl-XL, an antiapoptotic protein, without any significant change in the levels of Bcl-2.
Adhya
Amit Kumar
AK
Department of Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Srinivasan
Radhika
R
Patel
Firuza D
FD
D017209:Apoptosis / Q000235:genetics / Q000502:physiology / Q000528:radiation effects*; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000235:genetics / Q000473:pathology* / Q000532:radiotherapy*; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012044:Regression Analysis; D002583:Uterine Cervical Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology* / Q000532:radiotherapy*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism*
C494811:BCL2L1 protein, human; D004273:DNA, Neoplasm; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein