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Proliferation marker securin identifies favourable outcome in invasive ductal breast cancer.

Talvinen K, Tuikkala J, Nevalainen O, Rantanen A, Hirsimäki P, Sundström J, Kronqvist P - Br. J. Cancer (2008)

Bottom Line: Our results of a small sample of patients suggest that low securin expression identifies a distinct subgroup of more favourable outcome among patients with high Ki-67 immunoexpression or high MAI.In univariate analysis of Cox's regression, 10-unit increment of securin immunopositivity was associated with a 2.3-fold overall risk of death due to breast cancer and a 7.1-fold risk of death due to breast cancer in the sample of patients stratified according to the cutoff points of 10 and 20% of securin immunopositivity.The finding urges further prognostic studies with a large sample of patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Turku University Hospital, University of Turku, Kiinamyllynkatu 10, FIN-20520 Turku, Finland. kattal@utu.fi

ABSTRACT
We introduce a new proliferation marker, securin (pituitary tumour-transforming 1 (PTTG1)), analysed in invasive ductal breast carcinomas by cDNA microarrays and immunohistochemistry. In cDNA microarray of a total of 4000 probes of genes, securin was revealed with a significant change in expression among the several proliferation-related genes studied. The value of securin as a proliferation marker was verified immunohistochemically (n=44) in invasive ductal breast cancer. In follow-up analyses of the sample of patients, the prognostic value of securin was compared with the established markers of breast cancer proliferation, Ki-67 and mitotic activity index (MAI). Our results of a small sample of patients suggest that low securin expression identifies a distinct subgroup of more favourable outcome among patients with high Ki-67 immunoexpression or high MAI. In univariate analysis of Cox's regression, 10-unit increment of securin immunopositivity was associated with a 2.3-fold overall risk of death due to breast cancer and a 7.1-fold risk of death due to breast cancer in the sample of patients stratified according to the cutoff points of 10 and 20% of securin immunopositivity. We suggest that securin immunostaining is a promising and clinically applicable proliferation marker. The finding urges further prognostic studies with a large sample of patients.

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Related in: MedlinePlus

(A–C) Scatter plots with regression lines demonstrate differences in intermethod consistency between MAI and Ki-67 immunohistochemistry (A), securin immunohistochemistry and MAI (B), and securin and Ki-67 immunohistochemistry (C) for invasive ductal breast cancer cases (n=44).
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fig2: (A–C) Scatter plots with regression lines demonstrate differences in intermethod consistency between MAI and Ki-67 immunohistochemistry (A), securin immunohistochemistry and MAI (B), and securin and Ki-67 immunohistochemistry (C) for invasive ductal breast cancer cases (n=44).

Mentions: In immunohistochemical analysis, the average fraction of securin-positive cells was 10.9% (range 1.5–34.0) and that of Ki-67-positive cells 32.4% (range 4.0–80.0). Average MAI was 28.0 mitoses per 10 HPFs (range 2–141 mitoses per 10 HPFs). Consistency of evaluations as expressed in intra- and interobserver reproducibilities of each proliferation marker is summarised in Table 2. In our analysis, the intermethod reproducibility between MAI and Ki-67 was moderately high (ICC 0.5527, κw 0.2592; Figure 2A). Interpretations of proliferative activity, however, differed considerably between securin and MAI (ICC 0.1582, κw 0.1899; Figure 2B), and between securin and Ki-67 (ICC −0.2180, κw 0.0619; Figure 2C). In a detailed analysis, securin and Ki-67 resulted in 75% of cases differently allocated into groups of low, intermediate and high proliferation. Securin and MAI, in turn, allocated 64% of cases into different proliferation groups. In our analysis, the lowest consistency between observed proliferation rates was found among cases with low (<10%) securin expression and intermediate or high (⩾10%) Ki-67 expression (57% of cases), and low (<10%) securin expression and intermediate or high (⩾10%) MAI (45% of cases). Including the evaluation of the intensity of securin staining in the analysis did not improve statistical associations.


Proliferation marker securin identifies favourable outcome in invasive ductal breast cancer.

Talvinen K, Tuikkala J, Nevalainen O, Rantanen A, Hirsimäki P, Sundström J, Kronqvist P - Br. J. Cancer (2008)

(A–C) Scatter plots with regression lines demonstrate differences in intermethod consistency between MAI and Ki-67 immunohistochemistry (A), securin immunohistochemistry and MAI (B), and securin and Ki-67 immunohistochemistry (C) for invasive ductal breast cancer cases (n=44).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2480969&req=5

fig2: (A–C) Scatter plots with regression lines demonstrate differences in intermethod consistency between MAI and Ki-67 immunohistochemistry (A), securin immunohistochemistry and MAI (B), and securin and Ki-67 immunohistochemistry (C) for invasive ductal breast cancer cases (n=44).
Mentions: In immunohistochemical analysis, the average fraction of securin-positive cells was 10.9% (range 1.5–34.0) and that of Ki-67-positive cells 32.4% (range 4.0–80.0). Average MAI was 28.0 mitoses per 10 HPFs (range 2–141 mitoses per 10 HPFs). Consistency of evaluations as expressed in intra- and interobserver reproducibilities of each proliferation marker is summarised in Table 2. In our analysis, the intermethod reproducibility between MAI and Ki-67 was moderately high (ICC 0.5527, κw 0.2592; Figure 2A). Interpretations of proliferative activity, however, differed considerably between securin and MAI (ICC 0.1582, κw 0.1899; Figure 2B), and between securin and Ki-67 (ICC −0.2180, κw 0.0619; Figure 2C). In a detailed analysis, securin and Ki-67 resulted in 75% of cases differently allocated into groups of low, intermediate and high proliferation. Securin and MAI, in turn, allocated 64% of cases into different proliferation groups. In our analysis, the lowest consistency between observed proliferation rates was found among cases with low (<10%) securin expression and intermediate or high (⩾10%) Ki-67 expression (57% of cases), and low (<10%) securin expression and intermediate or high (⩾10%) MAI (45% of cases). Including the evaluation of the intensity of securin staining in the analysis did not improve statistical associations.

Bottom Line: Our results of a small sample of patients suggest that low securin expression identifies a distinct subgroup of more favourable outcome among patients with high Ki-67 immunoexpression or high MAI.In univariate analysis of Cox's regression, 10-unit increment of securin immunopositivity was associated with a 2.3-fold overall risk of death due to breast cancer and a 7.1-fold risk of death due to breast cancer in the sample of patients stratified according to the cutoff points of 10 and 20% of securin immunopositivity.The finding urges further prognostic studies with a large sample of patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Turku University Hospital, University of Turku, Kiinamyllynkatu 10, FIN-20520 Turku, Finland. kattal@utu.fi

ABSTRACT
We introduce a new proliferation marker, securin (pituitary tumour-transforming 1 (PTTG1)), analysed in invasive ductal breast carcinomas by cDNA microarrays and immunohistochemistry. In cDNA microarray of a total of 4000 probes of genes, securin was revealed with a significant change in expression among the several proliferation-related genes studied. The value of securin as a proliferation marker was verified immunohistochemically (n=44) in invasive ductal breast cancer. In follow-up analyses of the sample of patients, the prognostic value of securin was compared with the established markers of breast cancer proliferation, Ki-67 and mitotic activity index (MAI). Our results of a small sample of patients suggest that low securin expression identifies a distinct subgroup of more favourable outcome among patients with high Ki-67 immunoexpression or high MAI. In univariate analysis of Cox's regression, 10-unit increment of securin immunopositivity was associated with a 2.3-fold overall risk of death due to breast cancer and a 7.1-fold risk of death due to breast cancer in the sample of patients stratified according to the cutoff points of 10 and 20% of securin immunopositivity. We suggest that securin immunostaining is a promising and clinically applicable proliferation marker. The finding urges further prognostic studies with a large sample of patients.

Show MeSH
Related in: MedlinePlus