Lack of prognostic significance of the monoclonal antibody Ki-S1, a novel marker of proliferative activity, in node-negative breast carcinoma

Abstract

In a series of 205 node-negative breast cancers (NNBC), we determined staining by the novel antibody Ki-S1, a marker of tumor cell proliferation, in order to test its association with other prognostic variables and its prognostic significance. Ki-S1 was determined in routinely formalin-fixed paraffin-embedded tumor samples. Ki-S1 gave a nuclear staining in the majority of the carcinomas (188 of 205), with percentages of reacting nuclei ranging from 2% to 90% (median value of 7%). In 107 tumors frozen sections were available to also assess the Ki-67 antibody. Among these, 94 had a nuclear staining of cancer cells ranging from 5% to 80% (median value of 7%). In 46 tumors we also determined the MIB-1 antibody. The percentage of MIB-1 nuclear staining ranged from 1% to 50% (median value of 20%). There was no significant relationship between Ki-S1 and the other two cell kinetic markers. Ki-S1 labeling was significantly associated only with tumor size (p = 0.03). With a median follow-up of 6 years, Ki-S1 had no significant prognostic value for either relapse-free survival (RFS) or overall survival (OS) (Ki-S1 as continuous logarithmic variable; p = 0.86 and p = 0.23, respectively). For RFS the following variables had a significant prognostic value: Ki-67 (< or = 10% vs > 10%; p = 0.037); progesterone receptor (PgR) expression (- vs+/++; p = 0.041); tumor size (pT1 vs pT2-3; p = 0.042) and grading (GI vs GII-III; p = 0.047). For OS, tumor size (p = 0.0044), age (continuous variable; p = 0.0060), and Ki-67 (p = 0.043) were significantly prognostic. In multivariate analysis (final model), only tumor size retained a significant and independent prognostic value for RFS (p = 0.0042). For OS, both tumor size (p = 0.0029) and age (< or = 55 years vs > 55 years; p = 0.041) retained significance in the multivariate model. In conclusion, Ki-S1 does not seem to have prognostic relevance in this series of NNBC. Possible hypotheses to explain this observation are discussed.

Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients

“…Different antibodies were used through all trials: anti-Ki-67 was used in 24 studies (52.1%), anti-MIB-1 in 24 studies (52.1%), both antibodies were performed in five studies (Keshgegian and Cnaan, 1995;Veronese et al, 1995;Bevilacqua et al, 1996;Querzoli et al, 1996;Billgren et al, 2002), anti-Ki-S5 in two studies (Rudolph et al, 1999a;Esteva et al, 2004) and anti-Ki-S11 in one study (Rudolph et al, 1999b). The different cut-off values used were those of the authors (range: 3.5 -34%).…”

“…Out of the 38 evaluable studies for DFS (10 954 patients), subgroup analysis was possible in 15 studies with node-negative patients (3370 patients) (Sahin et al, 1991;Weikel et al, 1991Weikel et al, , 1995Gaglia et al, 1993;Bevilacqua et al, 1996;Brown et al, 1996;Pierga et al, 1996;Railo et al, 1997;Jansen et al, 1998;Clahsen et al, 1999;Harbeck et al, 1999;Rudolph et al, 1999a;Billgren et al, 2002;Trihia et al, 2003;Erdem et al, 2005), in eight with node-positive patients (1430 patients) (Weikel et al, 1991Gaglia et al, 1993;Pierga et al, 1996;Jansen et al, 1998;Billgren et al, 2002;Trihia et al, 2003;Esteva et al, 2004) and in six with untreated nodenegative patients (736 patients) (Sahin et al, 1991;Weikel et al, 1991;Bevilacqua et al, 1996;Railo et al, 1997;Jansen et al, 1998;Harbeck et al, 1999). Regarding OS (9472 patients), of all 35 studies, subgroup analysis was possible in nine studies with nodenegative patients (1996 patients) (Jensen et al, 1995;Weikel et al, 1995;Bevilacqua et al, 1996;Brown et al, 1996;Domagala et al, 1996;Fresno et al, 1997;Rudolph et al, 1999a;Trihia et al, 2003;Erdem et al, 2005), in four with node-positive patients (857 patients) Domagala et...…”

“…Regarding OS (9472 patients), of all 35 studies, subgroup analysis was possible in nine studies with nodenegative patients (1996 patients) (Jensen et al, 1995;Weikel et al, 1995;Bevilacqua et al, 1996;Brown et al, 1996;Domagala et al, 1996;Fresno et al, 1997;Rudolph et al, 1999a;Trihia et al, 2003;Erdem et al, 2005), in four with node-positive patients (857 patients) Domagala et al, 1996;Gonzalez et al, 2003;Trihia et al, 2003) and in two that included only untreated patients (node-negative and node-positive) (284 patients) (Pinder et al, 1995;Bevilacqua et al, 1996).…”

Prognostic value of proliferation in invasive breast cancer: a review

“…[53][54][55] Topoisomerase IIa is a recently established marker of proliferating cells. 56 In one study, topoisomerase IIa and Ki67 scores closely paralleled one another, indicating that the topoisomerase IIa labelling index reflects the proliferative activity of tumour cells.…”

How to Identify Patients With Increased Risk of Breast Cancer Relapse?

“…Other studies also pointed the importance of Ki-67 on relapse prediction and worse prognosis. 12 16,[29][30][31][32] Subtype classification related with regional relapse was also described. 16 In our sample, axillary dissection was performed in 295 patients (81.5%).…”