ORIGINAL ARTICLE

Association between histology grade, expression of HsMCM2, and cyclin A in human invasive breast carcinomas

I R K Bukholm¹, G Bukholm², R Holm³ and J M Nesland³

¹ Department of Surgery, Akershus University Hospital, 1474 Nordbyhagen, Norway
² Institute of Clinical Epidemiology and Molecular Biology, Akershus University Hospital, N-1474 Nordbyhagen, Norway
³ Department of Pathology, the Norwegian Radium Hospital, University of Oslo, 0316 Oslo, Norway

Correspondence to:
Correspondence to:
Dr I R K Bukholm, Department of Surgery, Akershus Central Hospital, 1474 Nordbyhagen, Norway;
ida.bukholm{at}klinmed.uio.no

Aim: 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.

Conclusion: 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.

Keywords: HsMCM2; breast carcinomas; immunohistochemistry; cyclin A; histology grade

Abbreviations: BCIP, 5-bromo 4-chloro-3indolyl-phosphatase; cdk, cyclin dependent kinase; CI, confidence interval; EF, elongation factor; HR, hazards ratio; MCM, minichromosome maintenance; NBT, nitroblue tetrazolium; PCNA, proliferating cell nuclear antigen

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