Downregulation of the anaphase-promoting complex (APC)7 in invasive ductal carcinomas of the breast and its clinicopathologic relationships.
BACKGROUND
The anaphase-promoting complex (APC) is a multiprotein complex with E3 ubiquitin ligase activity, which is required for the ubiquitination of securin and cyclin-B. Moreover, the mitotic spindle checkpoint is activated if APC activation is prevented. In addition, several APC-targeting molecules such as securin, polo-like kinase, aurora kinase, and SnoN have been reported to be oncogenes. Therefore, dysregulation of APC may be associated with tumorigenesis. However, the clinical significance and the involvement of APC in tumorigenesis have not been investigated.


METHODS
The expression of APC7 was immunohistochemically investigated in 108 invasive ductal carcinomas of the breast and its relationship with clinicopathologic parameters was examined. The expression of APC7 was defined as positive when the summed scores of staining intensities (0 to 3+) and stained proportions (0 to 3+) exceeded 3+.


RESULTS
Positive APC7 expression was less frequent than its negative expression when histologic (P = 0.009) or nuclear grade (P = 0.009), or mitotic number (P = 0.0016) was elevated. The frequency of APC7 negative expression was higher in high Ki-67 or aneuploid groups than in low Ki-67 or diploid groups.


CONCLUSIONS
These data show that loss of APC7 expression is more common in breast carcinoma cases with poor prognostic parameters or malignant characteristics. They therefore suggest that dysregulation of APC activity, possibly through downregulation of APC7, may be associated with tumorigenesis in breast cancer.
Park
Kwang-Hwa
KH
Department of Pathology, Yonsei University, Wonju, Korea. abba@wonju.yonsei.ac.kr
Choi
Sung-E
SE
Eom
Minseob
M
Kang
Yup
Y
D000328:Adult; D000368:Aged; D064173:Anaphase-Promoting Complex-Cyclosome; D000782:Aneuploidy; D064195:Apc7 Subunit, Anaphase-Promoting Complex-Cyclosome; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000502:physiology*
C577399:ANAPC7 protein, human; D064195:Apc7 Subunit, Anaphase-Promoting Complex-Cyclosome; D019394:Ki-67 Antigen; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome
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