Membranous and cytoplasmic staining of Ki67 is associated with HER2 and ER status in invasive breast carcinoma

Faratian, Dana; Munro, Alison; Twelves, Christopher; Bartlett, John M.S.

doi:10.1111/j.1365-2559.2008.03191.x

Cited by 60 publications

(72 citation statements)

References 12 publications

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“…These data are consistent with the findings of Faratian et al (42); however, Boland et al (13) observed the opposite, showing that cases with a high Ki-67 expression positively correlated with negative HR (p=0.003).…”

Section: Discussionsupporting

confidence: 82%

Interaction between cyclooxygenase-2 and insulin-like growth factor in breast cancer: A new field for prevention and treatment

et al. 2011

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Abstract. The objective of this study was to evaluate the correlation between cyclooxygenase-2 (COX-2) and markers of cell proliferation and apoptosis, including, Bcl-2, Bax, Ki-67 and the type I insulin-like growth factor (IGF) receptor (IGF1-R) in ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC), present in the same surgical specimen. A total of 110 cases were evaluated using tissue microarrays. Cases were classified in scores from 0 to 3 according to predefined methods. The results showed that the positivity rates were COX-2 in 87% of cases in DCIS and IDC; Bcl-2 in 55% of cases in DCIS and IDC; Bax in 23% of cases in IDC and 19% in DCIS, IGF-1 in 24% of cases in DCIS and IDC; and Ki-67 in 81% of cases in DCIS and IDC. We also observed a positive correlation between the expression of COX-2 and IGF1-R (p=0.045). Our results demonstrate a positive correlation between the expression of COX-2 and IGF1-R in DCIS and IDC, demonstrating that they are involved in breast cancer carcinogenesis. Further studies are required to prove the effectiveness of COX-2 and IGF1-R inhibitors for the prevention and treatment of breast cancer, as well as to explain their mechanism of action.

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Section: Discussionsupporting

confidence: 82%

Interaction between cyclooxygenase-2 and insulin-like growth factor in breast cancer: A new field for prevention and treatment

et al. 2011

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“…That Ki-67 is present during all active phases (G 1 , S, G 2 and mitosis) of the cell cycle, but absent in resting cells (G 0 ), makes it an excellent marker for determining the so-called growth fraction of a cell population (Scholzen & Gerdes 2000). Recently, membranous and cytoplasmic Ki-67 expression was described in studies of pathological conditions such as hyalinizing trabecular adenoma of the thyroid, sclerosing hemangioma of the lung, pleomorphic adenoma of the salivary gland, and in invasive ductal carcinomas of the breast (Hirokawa & Carney 2000;Hattori 2002;Tashiro et al 2002;Faratian et al 2009). While a relationship between membranous/cytoplasmic Ki-67 expression with other proteins has been noted (Faratian et al 2009), the mechanism of subcellular Ki-67 relocalization remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, membranous and cytoplasmic Ki-67 expression was described in studies of pathological conditions such as hyalinizing trabecular adenoma of the thyroid, sclerosing hemangioma of the lung, pleomorphic adenoma of the salivary gland, and in invasive ductal carcinomas of the breast (Hirokawa & Carney 2000;Hattori 2002;Tashiro et al 2002;Faratian et al 2009). While a relationship between membranous/cytoplasmic Ki-67 expression with other proteins has been noted (Faratian et al 2009), the mechanism of subcellular Ki-67 relocalization remains unclear. To date, mutations in the Ki-67 gene have not been described in order to explain an abnormal protein product with altered localization properties (Faratian et al 2009).…”

Section: Discussionmentioning

confidence: 99%

“…Ki-67 signal is usually observed in the nucleus of proliferating (during G 1 , S and G 2 phases) but non-mitotic normal cells and on the chromosomal surface in mitotic cells (Sholzen & Gerdes 2000). In some exceptional conditions, Ki-67 signal has also been detected in the cytoplasm of proliferating cells during the interphase (Grzanka et al 2000;Faratian et al 2009). For this reason, here, both cytoplasmic and nuclear signals were considered as positive if stain was identified.…”

Section: Immunoreactivity Evaluationmentioning

confidence: 99%

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Sex-based differences in lymphocyte proliferation in the spleen after vanadium inhalation

Rodríguez-Lara

Cambas

Villalva

et al. 2016

Journal of Immunotoxicology

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Vanadium (V) is a transition metal often adhered to particulate matter and released into the atmosphere as vanadium pentoxide (V 2 O 5 ) by the burning of fossil fuels. This air pollutant causes adverse effects in the immune system. Lymphocytosis and splenomegaly have been reported with increased white pulp in mice after V inhalation. The effect of V on the immune system as related to sex has been poorly investigated. This study sought to determine if V inhalation (a) produced lymphoproliferation that could explain the changes previously observed in the spleen and in peripheral blood lymphocyte counts and (b) whether any observed effects differed due to gender. Immunohistochemical analyses of Ki-67, a specific proliferation marker, was made in the spleens of CD-1 male and female mice exposed for 1 h, twice a week, over a 12-week period to V 2 O 5 (at 1.4 mg V 2 O 5 /m 3 ) by whole-body inhalation; similar analyses were performed on spleens of control mice exposed to vehicle (filtered air). The results showed that in male mice there was a significant increase in percentage of Ki-67 immunopositive lymphocytes starting from the second week and until the end of the exposure. The Ki-67 signal was cytoplasmic and nuclear in the exposed males, while in controls the signal was only nuclear. In female mice, V inhalation singificantly increased the percentage of proliferating lymphocytes only after 1 week of exposure. Ki-67 signal was observed only in the nucleus of lymphocytes from the control and exposed females. The results here help to explain the splenomegaly and lymphocytosis observed previously in male mice and support the lymphoproliferative effect induced by V. Lastly, the finding that there was a sex difference in the effect of vanadium on lymphocyte proliferation suggests a role for sex hormones in potential protection against V immunotoxicity; however, further studies are needed to support this hypothesis. ARTICLE HISTORY

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“…Therefore, immunostaining for MIB-1 has been generally used in diagnosing HTT. Of note, the aberrant staining pattern is also observed in breast carcinoma [9], salivary gland pleomorphic adenoma [10], and pulmonary sclerosing hemangiomas [11], but no diagnostic significance has been demonstrated. Leonardo et al described that crossreactivity of MIB-1 monoclonal antibody with a cell membrane epitope seems the most likely explanation for the findings [8].…”

Section: Discussionmentioning

confidence: 99%

Re-evaluation of MIB-1 immunostaining for diagnosing hyalinizing trabecular tumour of the thyroid: semi-automated techniques with manual antigen retrieval are more accurate than fully automated techniques

et al. 2018

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Abstract. Hyalinizing trabecular tumour (HTT) immunohistochemically shows cell membranous immunoreactivity for MIB-1. This aberrant immunoreactivity is an important factor for the diagnosis of HTT. However, fully automated stainers frequently fail to confirm the immunoreactivity. The aim of this study is to investigate the cause of false negative cell membranous immunoreactivity for MIB-1 in HTT using fully automated stainers, to determine potential reasons for the problem, and to establish methods confirming cell membranous immunoreactivity for MIB-1 in HTT. Six participating institutions examined immunoreactivity for MIB-1 in 10 HTT cases using two approaches: fully automated and semiautomated methods. In the latter, antigen retrieval was carried out using manual methods adopted for routine assays at each institute. The autostainers used included the BOND-MAX, BOND-III, Benchmark XT, and Omnis systems. Using fully automated methods, institute E showed cell membranous MIB-1 positivity in all HTT cases. In contrast, at institute D, all HTT cases were negative. The positive rates of the remaining four institutes ranged from 10% to 20%. The incidence of positive cases using semi-automated methods was 100%, 90%, 90%, 30%, 80%, and 100% at institutes A, B, C, D, E, and F, respectively. We assert that antigen retrieval should be conducted manually for diagnosis of HTT; furthermore, definitively diagnosed HTT should be prepared as the external positive control.

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Membranous and cytoplasmic staining of Ki67 is associated with HER2 and ER status in invasive breast carcinoma

Cited by 60 publications

References 12 publications

Interaction between cyclooxygenase-2 and insulin-like growth factor in breast cancer: A new field for prevention and treatment

Interaction between cyclooxygenase-2 and insulin-like growth factor in breast cancer: A new field for prevention and treatment

Sex-based differences in lymphocyte proliferation in the spleen after vanadium inhalation

Re-evaluation of MIB-1 immunostaining for diagnosing hyalinizing trabecular tumour of the thyroid: semi-automated techniques with manual antigen retrieval are more accurate than fully automated techniques

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