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MIB-1 proliferation index and the risk of lymph node metastasis in breast cancer
Prediction of lymph node status is an
important issue in breast cancer patients, and several papers in the
literature are concerned with both commonly used and non-conventional
predictive factors. However, many studies are retrospective, and often
include patients operated on over a long time period or in different
surgical units. In
order to
evaluate the potential risk factors for lymph node metastasis, 675
patients operated on consecutively between January 1995 and December 2002
were included in a prospective study.
All patients were operated on in the same Surgical Department, using a
standard technique for axillary lymph node dissection. The resected
specimens were processed in the Pathological Unit according to standard
procedure, and immunohistochemical analysis was conducted and evaluated by
the same pathologis, with the aim of minimizing potential bias related to
different methodological techniques and inter-observer reproducibility,
which is commonly found in immunohistochemistry. Similarly to the results of other studies,
LVI and pT stage were the most important predictors of lymph node
metastasis in our patients. In addition, the results of univariate and
multivariate analysis showed that MIB-1 expression could provide
additional information about the risk of axillary lymph node metastasis.
The effect of MIB-1 expression is particularly evident in the intermediate
risk groups (pT1c, pT2 without LVI), which may increase its clinical
utility. The incidence of nodal metastases in pT1c tumours with LVI and
MIB-1 positivity was 79%, which is similar to that of the highest risk
groups. On the contrary, the risk in MIB-1-negative pT2 tumours without
LVI was lower with respect to smaller tumours (pT1a-pT1b) with LVI. No
effect was found in very low or very high risk groups (pT1a-pT1b, pT2 with
LVI, and pT3-pT4). A strong correlation between MIB-1
expression and tumour grade was also observed in our cases. We assessed
the impact of MIB-1 expression on the risk of lymph node metastasis in
different grade subgroups amongst our patients and found a strong
difference between MIB-1 negative and positive cases in grade 2 tumours.
The risk of nodal metastasis in MIB-1-negative grade 2 cases was similar
to grade 1 tumours, whereas the risk in MIB-1-positive grade 2 cases was
similar to grade 3 tumours. This suggests that MIB-1 expression could
identify subgroups of grade 2 tumours with more aggressive clinical
behaviour. As such,
MIB-1
expression could be useful in distinguishing grade 2 tumours with
different biological aggressiveness, thus reducing problems related to
doubtful pathological grade allocations. In conclusion, the results of our
prospective study indicate that MIB-1 proliferation index may offer
additional informations about the risk of lymph node metastasis in breast
cancer, and could be useful in the identification of a more aggressive
phenotype of grade 2 tumours. Further studies about potential impact of
MIB-1 expression on disease-free and overall survival of patients are
ongoing.
Bibliographical reference:
Daniele
Marrelli Department of Human Pathology and Oncology, Section of Surgical Oncology, University of Siena, Italy
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