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Relationship of p53, Bcl-2, Ki-67 index and E-cadherin expression in early invasive breast cancers with comedonecrosis as an accelerated apoptosis
  1. N Hosaka1,
  2. T Ryu2,
  3. W Cui2,
  4. Q Li2,
  5. A Nishida2,
  6. T Miyake2,
  7. T Takaki2,
  8. M Inaba2,
  9. S Ikehara2
  1. 1Department of Clinical Pathology, Toyooka Hospital, Toyooka, Hyogo, Japan
  2. 2First Department of Pathology, Kansai Medical University, Moriguchi, Osaka, Japan
  1. Correspondence to:
 Dr Susumu Ikehara
 First Department of Pathology, Kansai Medical University, 10–15 Fumizono-Cho, Moriguchi, Osaka 570-8506, Japan; ikehara{at}


Aims: To study the relationship between comedonecrosis formation and morphology, apoptosis, and p53, Bcl-2, Ki-67 index and E-cadherin expression in early invasive breast cancer.

Experimental design: Early invasive breast cancers were first divided into two groups according to the presence (CN+ tumours) or absence (CN− tumours) of comedonecrosis. The histological grade, apoptosis, and expression of E-cadherin, Ki-67, p53 and Bcl-2 in the cancer-affected area, and in normal ducts from the specimen, were then examined.

Results: Less tubule and gland formation was seen in CN+ tumours than in CN− tumours, although the histological grade between the groups was not different. During early comedonecrosis, cells undergo apoptosis and subsequent necrosis. p53 was higher in CN+ tumours than in CN− tumours and normal ducts, whereas Bcl-2 was lower in CN+ tumours than in CN− tumours and normal ducts. Both tumours had higher Ki-67 than in normal ducts, but no difference was evident between the tumours. CN+ tumours had slightly higher E-cadherin than that in CN− tumours, but lower than that in normal ducts. The level of comedonecrosis was positively correlated with p53, but inversely correlated with Bcl-2 in all tumours, and p53 and Bcl-2 were inversely correlated with each other. Furthermore, comedonecrosis and p53 were correlated with Ki-67 in CN+ tumours, and Bcl-2 was correlated with Ki-67 in CN− tumours.

Conclusion: Comedonecrosis may be actively regulated through an apoptotic procedure in massive cancers for their survival and progression, and the above proteins may be associated cooperatively in this process. CN+ and CN− tumours may have opposite proliferative systems under the p53–Bcl-2 pathway.

  • HER2, human epidermal growth factor receptor 2
  • TUNEL, terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end-labelling
  • ssDNA, single-strand DNA

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  • Published Online First 10 February 2006