Association between histology grade, expression of HsMCM2, and cyclin A in human invasive breast carcinomas.
OBJECTIVE
Increased proliferation of tumour cells has prognostic value in human invasive breast carcinomas (IBCs), and high histology grade and cyclin A expression, which may reflect high proliferation rate, are associated with poor prognosis. Expression of HsMCM2 is related to cell proliferation. This study evaluates the correlation between the expression of cyclins A, D1, D3, and E, Ki-67, proliferating cell nuclear antigen (PCNA), histology grade, and HsMCM2 expression, in addition to the independent prognostic value of HsMCM2 expression in human IBCs.


METHODS
Immunohistochemistry to evaluate HsMCM2, Ki-67, and PCNA expression in tumours from 147 patients with IBC.


RESULTS
Nuclear staining for HsMCM2 was seen in 10-30% of the tumour cells in 30 samples, in 30-70% in 40 samples, in > 70% in 44 samples, and in < 10% in 33 samples. One way ANOVA showed a significant association between expression of HsMCM2 and cyclin A, D3, E, histology grade, and Ki-67. A borderline correlation was seen between HsMCM2 and PCNA. In multivariate analysis, the only association was with cyclin A, in addition to a borderline association with histology grade. In a Cox regression hazards model, expression of HsMCM2 was associated with poor patient survival, although it lost its independent prognostic value when cyclin A expression was included. Ki-67 and PCNA expression were not associated with patient survival.


CONCLUSIONS
Cyclin A expression is independently associated with HsMCM2 expression, histology grade, and Ki-67. HsMCM2 expression is associated with poor patient survival, although it loses prognostic value when adjusted for cyclin A.
Department of Surgery, Akershus University Hospital, 1474 Nordbyhagen, Norway. ida.bukholm@klinmed.uio.no
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Bukholm
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Bukholm
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Holm
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Nesland
D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D019925:Cyclin A / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D064111:Minichromosome Maintenance Complex Component 2; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D019925:Cyclin A; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D064111:Minichromosome Maintenance Complex Component 2