BGX–Ki-67 Index as a Supplementary Marker to MIB-1 Index, Enabling More Precise Distinction Between Luminal A and B Subtypes of Breast Carcinoma and Eliminating the Problem of Membranous/Cytoplasmic MIB-1 Staining

Niemiec, Joanna; Adamczyk, Agnieszka; Ambicka, Aleksandra; Mucha-Małecka, Anna; Wysocki, Wojciech M.; Majchrzyk, Kaja; Ryś, Janusz

doi:10.1309/ajcphaek82qwqorj

Cited by 4 publications

(11 citation statements)

References 30 publications

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“…The presence of membranous staining was correlated with histological grade 3, an ER-negative and a HER2positive status, although membranous staining failed to be an independent marker of poor prognosis in a multivariate model [14]. Another study with 27/136 (20%) membranous/ cytoplasmic staining rate of either primary breast and/or metastatic nodal carcinomas also found a similar association with the ER status [21].…”

Section: Discussionmentioning

confidence: 83%

“…When five antibodies were compared, the membranous staining was seen only with the MIB-1 antibodies from two different sources, and three other antibodies failed to give this staining in addition to the nuclear one [13]. In an independent study, MIB-1 was compared with a fourth monoclonal antibody, BGX-Ki67 (Biogenex, Fremont, CA, USA; 1:75 dilution), and again, membranous staining was only seen with MIB-1 [21]. The membranous/cytoplasmic staining with MIB-1 did not vanish with any of three different antigen retrieval methods, two different detection systems and in either of the two laboratories doing the staining [21].…”

Section: Discussionmentioning

confidence: 99%

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Analysis of membranous Ki-67 staining in breast cancer and surrounding breast epithelium

Cserni

2018

Virchows Arch

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Membranous Ki-67 staining with the MIB-1 antibody has been described in hyalinising trabecular adenomas of the thyroid and sclerosing haemangiomas of the lung. Its relatively rare occurrence in breast tumours has also been documented. The aim of the present study was to assess the rate of any membranous MIB-1 staining in breast specimens. The staining was performed at room temperature with 1:100 dilution of the antibody. One hundred four core needle biopsies and 41 operative specimens were analysed. Membranous staining was noted in 36/144 invasive carcinomas, 20/42 in situ carcinomas and 46/99 cases of peritumoural benign/normal breast epithelium. Most often, it presented as focal and partial polarised luminal membranous staining although complete circumferential staining also occurred, and membranous labelling was sometimes accompanied by cytoplasmic staining, too. In a few cases tested, greater dilution of the primary antibody did not abolish the membranous staining, which was absent with the SP6 monoclonal Ki-67 antibody. The membranous staining of invasive tumours showed no association with histological grade, lumen formation, oestrogen or progesterone receptor status or the Ki-67 nuclear labelling. In contrast, it was associated with a HER2-positive status, although it occurred in all molecular subtypes approached by immunohistochemistry. The background of this membranous staining remains elusive. It is unlikely to represent an artefact. At least partial sharing of an epitope of the nuclear Ki-67 protein with an unidentified membranous protein and some functional differences between membranous staining producing tumours and tumours lacking this pattern of staining may both contribute to some extent.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Analysis of membranous Ki-67 staining in breast cancer and surrounding breast epithelium

Cserni

2018

Virchows Arch

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“…13 The molecular mechanisms underlying this membranous and cytoplasmic or non-nuclear immmunoreactivity of Ki-67 detected in these tumors have still remained unknown; however, this immunolocalization has been proposed to represent the results of cross-reactivity of the MIB-1 clone with an epitope of Ki-67 antigen, ectopically expressed in the membrane of particular tumor types. 14 Coexistence of GP and SP is extremely rare. There has been only one case report of co-occurrence of bronchial papilloma and SP.…”

Section: Discussionmentioning

confidence: 99%

Coexistence of glandular papilloma and sclerosing pneumocytoma in the bronchiole

Kitawaki

Fujishima

Taniuchi

et al. 2018

Pathology International

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Both glandular papilloma (GP) and sclerosing pneumocytoma (SP) are rare tumors in the lung. We herein report an extremely rare case of coexistence of these two uncommon tumors. The patient was a 40-year-old Japanese woman with no chief complaint. A solitary nodule of the lung was detected using chest computed tomography. The transbronchial biopsy revealed that the tumor histologically corresponded to GP. The patient subsequently underwent partial resection of the right upper lobe. Histological examination of the resected specimens further revealed that the mass contained two different and independent elements and displayed typically histological features of GP and SP. Molecular analysis further revealed the presence of BRAF V600E and AKT1 E17K mutations in GP, whereas only AKT1 mutation was detected in SP. To our knowledge, this is the first case of coexistence of GP and SP in the bronchiole harboring common AKT1 mutation and different BRAF V600E mutational status.

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“…Studied group consist of HER2-overexpressing carcinomas, which are typically characterized by high proliferation, therefore Ki-67LI cut-off point (50%) in this study is relatively high. In our previous study analysing all subtypes, lower cut-off point was established 15.…”

Section: Resultsmentioning

confidence: 99%

Proteins Involved in HER2 Signalling Pathway, Their Relations and Influence on Metastasis-Free Survival in HER2-Positive Breast Cancer Patients Treated with Trastuzumab in Adjuvant Setting

et al. 2017

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Aim: Resistance to trastuzumab (which is a standard therapy for breast cancer patients with HER2 overexpression) is associated with higher risk of progression or cancer death, and might be related to activation of signalling cascades (PI3K/AKT/mTOR, Ras/Raf/MAPK) and decreased level of their inhibitors.Material and methods: Formalin-fixed paraffin-embedded tumour specimens from 118 HER2-overexpressing breast cancer patients treated with radical local therapy and trastuzumab in adjuvant setting were used for the assessment of: (1) PIK3CA gene mutations (p.H1047R and p.E545K) by qPCR, and (2) expression of Ki-67, EGFR, MUC4, HER3 and PTEN by immunohistochemistry.Results: Lower Ki-67LI was observed in EGFR-immunonegative and in PTEN-immunopositive tumours. MUC4-immunonegative tumours more frequently were PTEN- and HER3-immunonegative. Favourable metastasis-free survival was observed in patients with tumours characterized by Ki-67LI≤50% (p=0.027), HER3 immunonegativity or PTEN immunopositivity (vs. tumours with HER3 expression and lack of PTEN expression, p=0.043), additionally, the trend was observed for patients with pN0+pN1 pathological tumour stage (vs. pN2+pN3) (p=0.086). Cox model revealed that independent negative prognostic factors were: (i) Ki-67LI>50% (p=0.014, RR=4.6, 95% CI 1.4-15.4), (ii) HER3 immunopositivity together with PTEN immunonegativity (p=0.034, RR=3.7, 95% CI 1.1-12.5).Conclusion: The results of our study suggest that combined analysis of HER3 and PTEN expression might bring information on trastuzumab sensitivity in the group of HER2-positive breast cancer patients treated with trastuzumab in adjuvant setting.

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BGX–Ki-67 Index as a Supplementary Marker to MIB-1 Index, Enabling More Precise Distinction Between Luminal A and B Subtypes of Breast Carcinoma and Eliminating the Problem of Membranous/Cytoplasmic MIB-1 Staining

Cited by 4 publications

References 30 publications

Analysis of membranous Ki-67 staining in breast cancer and surrounding breast epithelium

Analysis of membranous Ki-67 staining in breast cancer and surrounding breast epithelium

Coexistence of glandular papilloma and sclerosing pneumocytoma in the bronchiole

Proteins Involved in HER2 Signalling Pathway, Their Relations and Influence on Metastasis-Free Survival in HER2-Positive Breast Cancer Patients Treated with Trastuzumab in Adjuvant Setting

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