Effects of hypoxia and its relationship with apoptosis, stem cells, and angiogenesis on the thymus of children with congenital heart defects: a morphological and immunohistochemical study.
BACKGROUND
The thymus slowly involutes with age after puberty. Various stress conditions accelerate the involution of the thymus and cause changes in the histologic structure of the gland.


OBJECTIVE
The present study performed histomorphological and immunohistochemical (IHC) evaluations of the thymus glands removed during surgical repair in patients with cyanotic or acyanotic congenital heart disease (CHD). The thymus glands in the hypoxic group were compared to those in the non-hypoxic group. This study suggested that the activation of HIF-1 alpha promotes tumor progression and impair prognosis due to the inhibition of apoptosis, increased population of stem cells, and induction of angiogenesis also suggested that inactivation of HIF-1 alpha in tumor-infiltrated tissues could halt tumor progression and improve prognosis.


METHODS
The study included 76 thymus glands removed from patients who underwent an operation due to CHD. Of these cases, 38 had cyanotic CHD, and constituted the hypoxic group. The remaining 38 patients had acyanotic CHD, and constituted the non-hypoxic group. IHC procedures were performed for HIF-1 alpha, FoxP3, CD44, Bcl-2, and CD34.


RESULTS
There were statistically significant differences between the hypoxic and non-hypoxic groups only in terms of medullary enlargement toward the cortex and effacement of the corticomedullary junction. In the immunohistochemical examination for five markers, staining intensity and staining rates increased with decreasing oxygen saturation.


CONCLUSIONS
It can be concluded that the activation of HIF-1 alpha promotes tumor progression and impair prognosis due to the inhibition of apoptosis, increased population of stem cells, and induction of angiogenesis.
Department of Pathology, Medeniyet University, Göztepe Training and Research Hospital İstanbul, Turkey.
A Bahar
AB
Ceyran
Department of Pathology, Medeniyet University, Göztepe Training and Research Hospital İstanbul, Turkey.
Serkan
S
Şenol
Department of Anesthesiology, Koşuyolu Training and Research Hospital İstanbul, Turkey.
Füsun
F
Güzelmeriç
Department of Pediatric Cardiac Surgery, Koşuyolu Training and Research Hospital İstanbul, Turkey.
Eylem
E
Tunçer
Department of Pediatric Cardiac Surgery, Koşuyolu Training and Research Hospital İstanbul, Turkey.
Aybala
A
Tongut
Department of Pediatric Cardiac Surgery, Koşuyolu Training and Research Hospital İstanbul, Turkey.
Babürhan
B
Özbek
Department of Anesthesiology, Koşuyolu Training and Research Hospital İstanbul, Turkey.
Ömer
Ö
Şavluk
Department of Pathology, Medeniyet University, Göztepe Training and Research Hospital İstanbul, Turkey.
Abdullah
A
Aydın
Department of Pediatric Cardiac Surgery, Koşuyolu Training and Research Hospital İstanbul, Turkey.
Hakan
H
Ceyran
D018952:Antigens, CD34 / Q000032:analysis; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002675:Child, Preschool; D003490:Cyanosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D006330:Heart Defects, Congenital / Q000150:complications / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D000860:Hypoxia / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D018919:Neovascularization, Physiologic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013234:Stem Cells / Q000737:chemistry / Q000473:pathology*; D013950:Thymus Gland / Q000098:blood supply / Q000737:chemistry / Q000473:pathology* / Q000601:surgery
D018952:Antigens, CD34; C000595707:BCL2 protein, human; D015415:Biomarkers; C497483:CD44 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C497442:HIF1A protein, human; D018960:Hyaluronan Receptors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019253:Proto-Oncogene Proteins c-bcl-2
Bcl-2; CD34; CD44; FoxP3; HIF-1 alpha; Hypoxia; angiogenesis; apoptosis; congenital heart defects; stem cells; thymus