Basal cytokeratin expression in relation to biological factors in breast cancer

Kuroda, Hajime; Ishida, Fumitaka; Nakai, Masami; Ohnisi, Kiyoshi; Itoyama, Shinji

doi:10.1016/j.humpath.2008.06.007

Cited by 17 publications

(7 citation statements)

References 34 publications

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“…The study's authors found that c‐Met overexpression was associated with a worse outcome but a direct relationship to molecular subtype was not made . Importantly, we found that patients with BL cancers in our cohort had many of the characteristics previously described in the literature, including younger age at presentation, larger tumor size, predilection for the histological category of IDC‐NST, high nuclear grade and mitotic rate, and increased p53 expression . Hence, our cohort appears to be representative of the BL phenotype and therefore our findings with regard to c‐Met expression could be extended to the wider population.…”

Section: Discussionmentioning

confidence: 49%

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C‐Met in invasive breast cancer

Ho-Yen

Green

Rakha

et al. 2013

Cancer

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BACKGROUND: Basal-like (BL) breast cancer is an aggressive form of breast cancer with limited treatment options. Recent work has identified BL breast cancer as a biologically distinct form of triple-negative breast cancer, with a worse outlook. The receptor tyrosine kinase c-Met is a novel therapeutic target associated with reduced survival in breast cancer. Few studies have specifically addressed the association between c-Met and molecular subtype of breast cancer, yet this is a key consideration when selecting patients for clinical trials. The aim of this study is to evaluate c-Met expression in a large cohort of invasive breast cancers and in particular, its correlation with molecular subtype. METHODS: Immunohistochemistry for c-Met was performed and evaluated on 1274 invasive breast cancers using tissue microarray technology. The c-Met scores were correlated with molecular subtype, survival, and other standard clinicopathological prognostic factors. RESULTS: Multivariate logistic regression showed c-Met was independently associated with BL status (odds ratio 5 6.44, 95% confidence interval 5 1.74-23.78, P 5.005). There was a positive correlation between c-Met and Her2 (P 5.005) and an inverse correlation with tumor size (P <.001). C-Met was an independent poor prognostic factor at Cox regression analysis in all subtypes (hazard ratio 5 1.85, 95% confidence interval 5 1.07-3.19, P 5.027) and there was a trend toward reduced survival in BL tumors overexpressing c-Met, but this was not significant. CONCLUSIONS: C-Met is independently associated with BL breast cancer. In the future, patients with BL tumors should be included in clinical trials of anti-c-Met therapy. Cancer 2014;120:163-71.

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Section: Discussionmentioning

confidence: 49%

“…We found an inverse correlation between c‐Met expression and tumor size. This finding was unexpected, given that BL tumors tend to be larger at presentation . Similar studies have found no relationship between c‐Met and tumor size .…”

Section: Discussionmentioning

confidence: 71%

C‐Met in invasive breast cancer

Ho-Yen

Green

Rakha

et al. 2013

Cancer

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“…Basal-like tumors have increased expression of P-glycoprotein, a protein related to multidrug resistance, compared to non-basal-like tumors (37). To examine the effect of NO on ER− breast cancer cell chemoresistance, serum-starved MDA-MB-231 cells were treated with DETANO or EGF for 24 hours and P-glycoprotein expression was measured by western blot.…”

Section: Resultsmentioning

confidence: 99%

S-Nitrosylation of EGFR and Src Activates an Oncogenic Signaling Network in Human Basal-Like Breast Cancer

Switzer

Glynn

Cheng

et al. 2012

Molecular Cancer Research

122

117

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Increased inducible nitric oxide synthase (NOS2) expression in breast tumors is associated with decreased survival of estrogen receptor-negative (ER−) breast cancer patients. We recently communicated the preliminary observation that nitric oxide (NO) signaling results in EGFR tyrosine phosphorylation. To further define the role of NO in the pathogenesis of ER− breast cancer, we examined the mechanism of NO-induced EGFR activation in human ER− breast cancer. NO was found to activate EGFR and Src by a mechanism that includes S-nitrosylation. NO, at physiologically relevant concentrations, induced an EGFR/Src-mediated activation of oncogenic signal transduction pathways (including c-Myc, Akt and β-catenin) and the loss of PP2A tumor suppressor activity. Additionally, NO signaling increased cellular EMT, expression and activity of COX-2 and chemoresistance to adriamycin and paclitaxel. When connected into a network, these concerted events link NO to the development of a stem cell-like phenotype, resulting in the upregulation of CD44 and STAT3 phosphorylation. Our observations are also consistent with the finding that NOS2 is associated with a basal-like transcription pattern in human breast tumors. These results indicate that the inhibition of NOS2 activity or NO signaling networks may have beneficial effects in treating basal-like breast cancer patients.

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“…The only study with a higher basal prevalence was Carey et al , with 20.1% [17]. Tan et al [53] demonstrated that increased levels of Ki 67 show a correlation with immuno-negativity for estrogen receptors, high tumor grade and increased mitotic activity, while in another study Kuroda et al [54] showed high levels of Ki-67, p-53 and P-glycoprotein more in basal than in non basal types of breast cancer. In our study too the Ki-67 index was highest in the basal type followed by HER2, hybrids, LUMB, UC and finally LUMA.…”

Section: Discussionmentioning

confidence: 99%

Protein expression profile and prevalence pattern of the molecular classes of breast cancer - a Saudi population based study

et al. 2010

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BackgroundBreast cancer is not a single entity but a diverse group of entities. Advances in gene expression profiling and immunohistochemistry as its surrogate marker have led to the unmasking of new breast cancer molecular subtypes, resulting in the emergence of more elaborate classification systems that are therapeutically and prognostically more predictive. Molecular class distribution across various ethnic groups may also reveal variations that can lead to different clinical outcomes in different populations.MethodsWe aimed to analyze the spectrum of molecular subtypes present in the Saudi population. ER, PR, HER2, EGFR and CK5/6 were used as surrogate markers for gene expression profiling to classify 231 breast cancer specimens. Correlation of each molecular class with Ki-67 proliferation index, p53 mutation status, histologic type and grade of the tumor was also carried out.ResultsOut of 231 cases 9 (3.9%) were classified as luminal A (strong ER +ve, PR +ve or -ve), 37 (16%) as luminal B (weak to moderate ER +ve, and/or PR +ve), 40 (17.3%) as HER2+ (strong or moderately positive HER 2 with confirmation by silver enhanced in-situ hybridization) and 23 (10%) as basal (CK5/6 or EGFR +ve). Co-positivity of different markers in varied patterns was seen in 23 (10%) of cases which were grouped into a hybrid category comprising luminal B-HER2, HER2-basal and luminal-basal hybrids. Ninety nine (42.8%) of the tumors were negative for all five immunohistochemical markers and were labelled as unclassified (penta negative). A high Ki-67 proliferation index was seen in basal (p = 0.007) followed by HER2+ class. Overexpression of p53 was predominantly seen in HER2 + (p = 0.001) followed by the basal group of tumors. A strong correlation was noted between invasive lobular carcinoma and hormone receptor expression with 8 out of 9 lobular carcinoma cases (88.9%) classifiable as luminal cancers. Otherwise, there was no association between the molecular class and the histologic type or grade of the tumor.ConclusionsSubtyping by use of this immunohistochemical panel revealed a prevalence pattern that is unique to our population; luminal tumors comprised only 19.9%, and the unclassified group (penta negative) 42.8%, a distribution which is distinctive to our population and in contrast with all Western studies. The presence of a predominant unclassified group also suggests that the currently used molecular analytic spectrum may not completely encompass all molecular classes and there is a need to further refine and develop the existing classification systems.

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Basal cytokeratin expression in relation to biological factors in breast cancer

Cited by 17 publications

References 34 publications

C‐Met in invasive breast cancer

C‐Met in invasive breast cancer

S-Nitrosylation of EGFR and Src Activates an Oncogenic Signaling Network in Human Basal-Like Breast Cancer

Protein expression profile and prevalence pattern of the molecular classes of breast cancer - a Saudi population based study

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