Prognostic significance of geminin expression levels in Ki67-high subset of estrogen receptor-positive and HER2-negative breast cancers

Yagi, Tomoko; Inoue, Nobuyuki; Yanai, Ayako; Murase, K; Imamura, Michiko; Miyagawa, Yoshimasa; Enomoto, Yukie; Nishimukai, Arisa; Takatsuka, Yuichi; Hirota, Seiichi; Akazawa, Kouhei; Miyoshi, Yasuo

doi:10.1007/s12282-014-0556-9

Cited by 12 publications

(11 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our data are also in line with studies that showed an association between increased immunohistochemical expression of AURKB and shorter survival in head and neck [31], laryngeal [32], lung [33], hepatocellular [34], biliary tract [35], endometrial [36], and ovarian cancer [37]. Similarly, our results are consistent with association between high GMNN level and shorter survival in breast [38], penile [39], renal cell [40], and other cancers, reviewed by Kapoor [41] and Petropoulou et al [20].…”

Section: Discussionsupporting

confidence: 92%

High proliferation index, as determined by immunohistochemical expression of Aurora kinase B and geminin, indicates poor prognosis in neuroblastomas

2015

View full text Add to dashboard Cite

Expression profile analysis of cell cycle biomarkers provides a powerful index of the proliferative state of tumors, which is linked to disease aggressiveness. We investigated the impact of the biomarkers of S-G2-M phases of cell cycle, Aurora kinase B (AURKB) and geminin (GMNN), on disease progression in neuroblastomas. The expression of AURKB and GMNN was studied by immunostaining 84 neuroblastomas. A proliferation index (PI) was obtained on scanned immunostained slides using image analysis software. The median PI was 8.5 % for AURKB- and 16.8 % for GMNN-stained slides with a high correlation between the two (r s = 0.72, P < 0.001). The PI for both markers was significantly higher in neuroblastomas from patients with unfavorable clinical (high-risk group, advanced stage, age ≥18 months at presentation, primary abdominal compared to extra-abdominal sites), biological (MYCN amplification, 1p deletion, 17q gain), and pathological (undifferentiated or poorly differentiated status, high mitosis-karyorrhexis index, [MKI], unfavorable histology) factors. Using Cox regression models, a higher-than-median AURKB and GMNN PI was associated with a significantly shorter overall survival (OS) and event-free survival (EFS) in univariable analysis. In multivariable analysis, a high AURKB PI was associated with significantly shorter OS and EFS, independent of MYCN amplification, and significantly shorter EFS, independent of MKI. High GMNN PI was also associated with significantly shorter OS and EFS after adjusting for MYCN amplification but failed to reach statistical significance after adjusting for MKI. Our study shows that in neuroblastomas, AURKB- or GMNN-based PI provides valuable prognostic information and high PI indicates aggressive disease.

show abstract

Section: Discussionsupporting

confidence: 92%

High proliferation index, as determined by immunohistochemical expression of Aurora kinase B and geminin, indicates poor prognosis in neuroblastomas

2015

View full text Add to dashboard Cite

show abstract

“…Details of the methods used for immunostaining of pS6, pMAPK and TP53 have been described in a previous report [ 23 ]. For immunohistochemical staining of geminin, a rabbit anti-Geminin antibody (FL-209, diluted 1:200; Santa Cruz Biotechnology, Santa Cruz, CA) was used by following a method described elsewhere [ 24 ].…”

Section: Methodsmentioning

confidence: 99%

Tumor size and proliferative marker geminin rather than Ki67 expression levels significantly associated with maximum uptake of 18F-deoxyglucose levels on positron emission tomography for breast cancers

et al. 2017

Self Cite

View full text Add to dashboard Cite

It has been well established that maximum standardized uptake value (SUVmax) for 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) is clinically useful for evaluating treatment efficacy as well as predicting prognosis of breast cancer patients. Although SUVmax reflects increased glucose uptake and metabolism possibly induced by activation of growth factor signaling or TP53 dysfunction, tumor characteristics of SUVmax-high breast cancers remain to be elucidated. For the present study, we used immunohistochemical staining to investigate expressions of phospho-ribosomal protein S6 (pS6, downstream molecule of phosphatidyl inositol 3-kinase/Akt/mammalian target of the rapamycin/S6K pathway) and phosphor-p44/42 mitogen-activated protein kinase (pMAPK). Expression levels of TP53 and proliferative marker geminin as well as Ki67 were also examined by means of immunostaining in 163 invasive breast cancers. Cutoff values were set at 10% for pS6, 20% for pMAPK and TP53, and 4% for geminin. The SUVmax levels were significantly higher in the pS6-positive (p = 0.0173), TP53-positive (p = 0.0207) and geminin-high cancers (p<0.0001), but there was no significant association between pMAPK expression levels and SUVmax levels. Multivariable analysis showed that a high geminin level (odds ratio: 6.497, 95% confidence interval: 2.427–19.202, p = 0.0001) and large tumor size (6.438, 2.224–20.946, p = 0.0005) were significantly and independently associated with SUVmax-high. Univariable but not multivariable analysis indicated that Ki67-high significantly correlated with SUVmax-high. Twenty of 23 (87.0%) breast cancers with tumor size >2cm and geminin-high showed SUVmax-high, while only 6 of 49 (12.2%) breast cancers ≤2cm in size and with low geminin levels were SUVmax-high. In conclusion, we could determine that breast cancers with a large tumor and a geminin-high rather than Ki67-high proliferative marker were significantly associated with high levels of SUVmax. These findings may signify that SUVmax reflects tumor characteristics with high proliferative activity but not activation of mTOR/S6K and MAPK pathways or increased glucose metabolism due to dysfunction of TP53.

show abstract

“…Ki-67 is a nuclear protein associated with proliferation that is an established prognostic biomarker in various human tumor types, including breast cancer, lymphoma and neuroendocrine neoplasia (33)(34)(35). Previously, a high Ki-67 index was reported to predict reduced disease-free and overall survival in intestinal-type gastric cancer (35) and advanced gastric cancer (33).…”

Section: Ihc Score (24) ---------------------------------------------mentioning

confidence: 99%

Differential expression of EphA5 protein in gastric carcinoma and its clinical significance

et al. 2019

View full text Add to dashboard Cite

The aim of the present study was to evaluate ephrin type-A receptor 5 (EphA5) expression and its clinicopathological significance in gastric cancer. Gastric cancer tissues were analyzed by immunohistochemistry. The association between EphA5 expression and clinicopathological parameters, human epidermal growth factor receptor 2 (HER2) status and Ki-67 proliferation index was statistically analyzed. EphA5 expression was detected in all non-tumor gastric epithelia but was differentially expressed among gastric cancer samples. EphA5 was negatively expressed in 30/110 (27.3%) and positively expressed in 80/110 (72.3%) samples from patients with gastric cancer. EphA5 expression was significantly associated with Lauren classification (P= 0.032), lymph node metastasis (P<0.001), HER2 expression (P=0.020) and Ki-67 expression (P=0.005). No significant association was determined between EphA5 expression and age, sex, primary location, depth of invasion and Tumor-Node-Metastasis stage. The present data indicated that EphA5 is differentially expressed in gastric cancer. EphA5 may therefore be a potential therapeutic target and may have clinical utility as a marker for lymph node metastasis in gastric cancer.

show abstract

Prognostic significance of geminin expression levels in Ki67-high subset of estrogen receptor-positive and HER2-negative breast cancers

Cited by 12 publications

References 15 publications

High proliferation index, as determined by immunohistochemical expression of Aurora kinase B and geminin, indicates poor prognosis in neuroblastomas

High proliferation index, as determined by immunohistochemical expression of Aurora kinase B and geminin, indicates poor prognosis in neuroblastomas

Tumor size and proliferative marker geminin rather than Ki67 expression levels significantly associated with maximum uptake of 18F-deoxyglucose levels on positron emission tomography for breast cancers

Differential expression of EphA5 protein in gastric carcinoma and its clinical significance

Contact Info

Product

Resources

About