Markers of progression in early-stage invasive breast cancer: a predictive immunohistochemical panel algorithm for distant recurrence risk stratification

Aleskandarany, Mohammed A.; Soria, Daniele; Green, Andrew; Nolan, Chris; Diez-Rodriguez, Maria; Ellis, Ian O.; Rakha, Emad A.

doi:10.1007/s10549-015-3406-3

Cited by 23 publications

(15 citation statements)

References 29 publications

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“…Most notably, we have found that Tomm34 associates with poor survival of patients with p53-mutant ovarian cancers. These data are also comparable to the findings that Tomm34 is a marker of poor outcome and a predictor of distant metastasis in breast cancer [22,23]. Thus, as with breast cancer patients, The mechanism for high level expression of Tomm34 is unclear from our studies.…”

Section: Discussionsupporting

confidence: 88%

“…Subsequent studies have shown that Tomm34 interacts with both Hsp70 and Hsp90 and modifies their protein folding activities [16][17][18][19][20]. In cancer, high levels of Tomm34 have been reported in bladder, colorectal and breast cancers compared to their normal tissue counterparts [21][22][23][24][25][26]. In these cancers, Tomm34 promotes colorectal cancer cell growth [21] and is a biomarker of poor outcome in early invasive breast cancer [22] and bladder cancer [26].…”

Section: Introductionmentioning

confidence: 99%

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Tomm34 is commonly expressed in epithelial ovarian cancer and associates with tumour type and high FIGO stage

et al. 2019

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Background: Increased activity of the chaperones Hsp70 and Hsp90 is a common feature of solid tumours. Translocase of the outer mitochondrial membrane 34 (Tomm34) is a cochaperone of both Hsp70 and Hsp90 that was found to be overexpressed in colorectal, hepatocellular, lung and breast carcinomas. The expression profile of Tomm34 in ovarian cancer has not been investigated. Therefore, the aim of the current study was to investigate the expression pattern of Tomm34 in ovarian carcinomas and analyse its correlation with clinico-pathological parameters. Results: Epithelial ovarian cancers (140) were histologically classified based on their morphology and graded into two types comprising 5 histologic subgroups. Type I carcinomas comprise low grade serous (LGSC), clear cell (CCOC) and endometrioid (ENOC), type II comprises high grade serous carcinomas (HGSC) and solid, pseudoendometrioid, transitional carcinomas (SET). Tomm34 was more highly expressed in type II than type I carcinomas (p < 0.0001). Comparing tumours based on the mutation in the TP53 gene revealed similar results, where mutant tumours exhibited significantly higher levels of Tomm34 (p < 0.0001). The decreased levels of Tomm34 in type I carcinomas were particularly evident in clear cell and mucinous carcinomas. The expression of Tomm34 was also positively correlated with FIGO stage (r = 0.23; p = 0.007). Tomm34 levels also indicated poor prognosis for patients with mutant p53. Conclusions: Our data indicate that Tomm34 is commonly expressed at high levels in epithelial ovarian cancers, except for the clear cell and mucinous subtypes. The expression of Tomm34 corresponds with the dualistic model of ovarian cancer pathogenesis where high grade, type II tumours exhibit higher expression of Tomm34 in contrast to type I tumours. These data are also comparable to the previous findings that Tomm34 is a marker of progression and poor prognosis in human cancer.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Tomm34 is commonly expressed in epithelial ovarian cancer and associates with tumour type and high FIGO stage

et al. 2019

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“…Similar to the clinical scenario of breast tumours, the Walker 256 cell line expressed genes of several prognostic/therapeutic/invasiveness markers of breast cancer, while some of the common genes were absent (genes were considered to be above the noise level only if the read count was ≥ 10; so gene count < 10 might be considered to be noise, and hence the corresponding gene is considered to be absent) (Figure ).…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic characterisation of the optimised rat model of Walker 256 breast cancer cell‐induced bone pain

Shenoy

Kuo

Leparc

et al. 2019

Clin Exp Pharma Physio

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In patients with breast cancer, metastases of cancer cells to the axial skeleton may cause excruciating pain, particularly in the advanced stages. The current drug treatments available to alleviate this debilitating pain condition often lack efficacy and/or produce undesirable side effects. Preclinical animal models of cancer‐induced bone pain are key to studying the mechanisms that cause this pain and for the success of drug discovery programs. In a previous study conducted in our laboratory, we validated and characterised the rat model of Walker 256 cell‐induced bone pain, which displayed several key resemblances to the human pain condition. However, gene level changes that occur in the pathophysiology of cancer‐induced bone pain in this preclinical model are unknown. Hence, in this study, we performed the transcriptomic characterisation of the Walker 256 cell line cultured in vitro to predict the molecular genetic profile of this cell line. We also performed transcriptomic characterisation of the Walker 256 cell‐induced bone pain model in rats using the lumbar spinal cord and lumbar dorsal root ganglia tissues. Here we show that the Walker 256 cell line resembles the basal‐B molecular subtype of human breast cancer cell lines. We also identify several genes that may underpin the progression of pain hypersensitivities in this condition, however, this needs further confirmatory studies. These transcriptomic insights have the potential to direct future studies aimed at identifying various mechanisms underpinning pain hypersensitivities in this model that may also assist in discovery of novel pain therapeutics for breast cancer‐induced bone pain.

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“…BCL2 expression has been associated with prognostication of disease-free survival, overall survival, and recurrence in BC 71–78. Moreover, normal breast tissue from women with BC was reported to display higher levels of BCL2 expression than breast tissue from women with no evidence of cancer 79.…”

Section: Discussionmentioning

confidence: 99%

An exploratory study of host polymorphisms in genes that clinically characterize breast cancer tumors and pretreatment cognitive performance in breast cancer survivors

Koleck

Bender

Clark

et al. 2017

BCTT

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PurposeInspired by the hypothesis that heterogeneity in the biology of breast cancers at the cellular level may account for cognitive dysfunction symptom variability in survivors, the current study explored relationships between host single-nucleotide polymorphisms (SNPs) in 25 breast cancer-related candidate genes (AURKA, BAG1, BCL2, BIRC5, CCNB1, CD68, CENPA, CMC2, CTSL2, DIAPH3, ERBB2, ESR1, GRB7, GSTM1, MELK, MKI67, MMP11, MYBL2, NDC80, ORC6, PGR, RACGAP1, RFC4, RRM2, and SCUBE2), identified from clinically relevant prognostic multigene-expression profiles for breast cancer, and pretreatment cognitive performance.Patients and methodsThe sample (n=220) was comprised of 138 postmenopausal women newly diagnosed with early stage breast cancer and 82 postmenopausal age- and education-matched healthy controls without breast cancer. Cognitive performance was assessed after primary surgery but prior to initiation of adjuvant chemotherapy and/or hormonal therapy using a comprehensive battery of neuropsychological tests encompassing eight cognitive function composite domains: attention, concentration, executive function, mental flexibility, psychomotor speed, verbal memory, visual memory, and visual working memory. In total, 131 SNPs were included in the analysis. Standard and robust multiple linear regression modeling was used to examine relationships between each domain and the presence or absence of one or more minor alleles for each SNP. Genetic risk/protection scores (GRSs) were calculated for each domain to evaluate the collective effect of possession of multiple risk/protective alleles.ResultsWith the exception of CMC2, MMP11, and RACGAP1, significant (P<0.05) SNP main effect and/or SNP by future prescribed treatment group interactions were observed for every gene between at least one domain and one or more SNPs. All GRSs were found to be significantly (P<0.001) associated with each respective domain score.ConclusionAssociations between host SNPs and computed GRSs and variability in pretreatment cognitive function performance support the study hypothesis, and warrant further investigations to identify biomarkers for breast cancer-related cognitive dysfunction.

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Markers of progression in early-stage invasive breast cancer: a predictive immunohistochemical panel algorithm for distant recurrence risk stratification

Cited by 23 publications

References 29 publications

Tomm34 is commonly expressed in epithelial ovarian cancer and associates with tumour type and high FIGO stage

Tomm34 is commonly expressed in epithelial ovarian cancer and associates with tumour type and high FIGO stage

Transcriptomic characterisation of the optimised rat model of Walker 256 breast cancer cell‐induced bone pain

An exploratory study of host polymorphisms in genes that clinically characterize breast cancer tumors and pretreatment cognitive performance in breast cancer survivors

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