Epidermal growth factor receptor gene polymorphisms are associated with prognostic features of breast cancer

Sobral-Leite, Marcelo; Giacomin, Letícia Carlos; Piranda, Diogo Nascimento; Festa-Vasconcellos, Juliana S.; Indio-do-Brasil, Vanessa; Koifman, Sérgio; Carvalho, Marcelo A.; Vianna‐Jorge, Rosane

doi:10.1186/1471-2407-14-190

Cited by 13 publications

(19 citation statements)

References 41 publications

(42 reference statements)

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“…The TME stimulus was induced by simultaneous exposure of luminal-A breast tumor cells to representatives of 3 relevant arms of the TME: 1) estrogen, the key hormonal factor in luminal-A tumors, which by definition, all express ER [18,19]; 2) TNF-a, a representative of the inflammatory arm; this cytokine has direct tumor-promoting effects in breast cancer and is expressed by ;90% of breast cancer patients with recurrent disease, including ER+ breast tumors [39][40][41][42][43]; and 3) EGF, a growth-stimulating factor that prevails in breast tumors [44,45]. Luminal-A tumors express EGFR and are characterized by high levels of ErbB3 [46][47][48]. EGF was shown to act through EGFR-ErbB3 dimers in luminal-A breast tumor cells [46] and to induce signaling in such cells through indirect activation of ER [48][49][50][51][52].…”

Section: Introductionmentioning

confidence: 99%

Chemokine axes in breast cancer: factors of the tumor microenvironment reshape the CCR7-driven metastatic spread of luminal-A breast tumors

Weitzenfeld

Kossover

Körner

et al. 2016

Journal of Leukocyte Biology

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Chemokine axes have been shown to mediate site-specific metastasis in breast cancer, but their relevance to different subtypes has been hardly addressed. Here, with the focus on the CCR7-CCL21 axis, patient datasets demonstrated that luminal-A tumors express relatively low CCR7 levels compared with more aggressive disease subtypes. Furthermore, lymph node metastasis was not associated with high CCR7 levels in luminal-A patients. The metastatic pattern of luminal-A breast tumors may be influenced by the way luminal-A tumor cells interpret signals provided by factors of the primary tumor microenvironment. Thus, CCR7-expressing human luminal-A cells were stimulated simultaneously by factors representing 3 tumor microenvironment arms typical of luminal-A tumors, hormonal, inflammatory, and growth stimulating: estrogen + TNF-α + epidermal growth factor. Such tumor microenvironment stimulation down-regulated the migration of CCR7-expressing tumor cells toward CCL21 and inhibited the formation of directional protrusions toward CCL21 in a novel 3-dimensional hydrogel system. CCL21-induced migration of CCR7-expressing tumor cells depended on PI3K and MAPK activation; however, when CCR7-expressing cancer cells were prestimulated by tumor microenvironment factors, CCL21 could not effectively activate these signaling pathways. In vivo, pre-exposure of the tumor cells to tumor microenvironment factors has put restraints on CCL21-mediated lymph node-homing cues and shifted the metastatic pattern of CCR7-expressing cells to the aggressive phenotype of dissemination to bones. Several of the aspects were also studied in the CXCR4-CXCL12 system, demonstrating similar patient and in vitro findings. Thus, we provide novel evidence to subtype-specific regulation of the CCR7-CCL21 axis, with more general implications to chemokine-dependent patterns of metastatic spread, revealing differential regulation in the luminal-A subtype.

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Section: Introductionmentioning

confidence: 99%

Chemokine axes in breast cancer: factors of the tumor microenvironment reshape the CCR7-driven metastatic spread of luminal-A breast tumors

Weitzenfeld

Kossover

Körner

et al. 2016

Journal of Leukocyte Biology

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“…Furthermore, EGFR genetic polymorphisms have shown a predictive value for the risk of breast cancer [16]. A previous case-control study revealed that cases with a polymorphism at nucleotide 2607 in EGFR exon 20 (G2607A; Q787Q; rs 10251977) are more susceptible to lung cancer [17].…”

Section: Introductionmentioning

confidence: 99%

Q787Q EGFR Polymorphism as a Prognostic Factor for Lung Squamous Cell Carcinoma

Koh

Kim²,

Kwon³

et al. 2016

Oncology

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Objective: EGFR genetic polymorphisms have been investigated for carcinogenesis in various tumors including lung cancer. We evaluated EGFR mutations in four exons, with an emphasis on the Q787Q EGFR polymorphism in non-small-cell lung cancer. Methods: To determine the presence of the Q787Q polymorphism in patients with lung cancer, we performed direct sequencing analyses of four exons for 83 squamous cell carcinomas and 80 adenocarcinomas untreated with EGFR tyrosine kinase inhibitors. Results: The Q787Q EGFR polymorphism was more frequently detected in squamous cell carcinoma patients than in adenocarcinoma patients (24 vs. 15.9%). The group of patients with the Q787Q EGFR polymorphism included more males and heavy smokers compared with other patient groups. The presence of the Q787Q EGFR polymorphism significantly and negatively affected the overall survival rate among patients with non-small-cell carcinoma (p = 0.011), particularly those with squamous cell carcinoma (p = 0.037). Among stage I and II squamous cell carcinoma patients, those with the Q787Q EGFR polymorphism had a poor prognosis (p = 0.032). Conclusions: The Q787Q EGFR polymorphism allows stratifying lung squamous cell carcinoma patients and could be an independent prognostic marker, particularly among those in stages I and II.

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“…41 in our series was treated in second line with Cetuximab with partial response (8). In other tumor systems, the integrated assessment of egfr polymorphisms, histopathological features and staging factors were shown to contribute to prognostic estimates in breast cancer (27). Our pilot study data indicated that egfr short CA-SSR-1 sequences were significantly associated with the more aggressive B2/B3, B3 and B3/C WHO histotype groups (28) Furthermore, egfr-FISH positivity was associated with malignant behaviour in thymomas in 5 out of the 7 cases with available FU.…”

Section: Discussionmentioning

confidence: 75%

Molecular genetic alterations in egfr CA-SSR-1 microsatellite and egfr copy number changes are associated with aggressiveness in thymoma

Conti¹,

Gallo²,

Sioletic

et al. 2016

J. Thorac. Dis.

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Background: The key role of egfr in thymoma pathogenesis has been questioned following the failure in identifying recurrent genetic alterations of egfr coding sequences and relevant egfr amplification rate. We investigated the role of the non-coding egfr CA simple sequence repeat 1 (CA-SSR-1) in a thymoma case series. Methods: We used sequencing and egfr-fluorescence in situ hybridization (FISH) to genotype 43 thymomas; (I) for polymorphisms and somatic loss of heterozygosity of the non-coding egfr CA-SSR-1 microsatellite and (II) for egfr gene copy number changes. Results: We found two prevalent CA-SSR-1 genotypes: a homozygous 16 CA repeat and a heterozygous genotype, bearing alleles with 16 and 20 CA repeats. The average combined allele length was correlated with tumor subtype: shorter sequences were significantly associated with the more aggressive WHO thymoma subtype group including B2/B3, B3 and B3/C histotypes. Four out of 29 informative cases analysed for somatic CA-SSR-1 loss of heterozygosity showed allelic imbalance (AI), 3/4 with loss of the longer allele.By egfr-FISH analysis, 9 out of 33 cases were FISH positive. Moreover, the two integrated techniques demonstrated that 3 out of 4 CA-SSR-1-AI positive cases with short allele relative prevalence showed significantly low or high chromosome 7 "polysomy"/increased gene copy number by egfr-FISH. Conclusions: Our molecular and genetic and follow up data indicated that CA-SSR-1-allelic imbalance with short allele relative prevalence significantly correlated with EGFR 3+ immunohistochemical score, increased egfr Gene Copy Number, advanced stage and with relapsing/metastatic behaviour in thymomas.Keywords: Thymoma; thymic epithelial tumors (TET); egfr microsatellite CA-SSR-1; allelic imbalance (AI); loss of heterozygosity; egfr-fluorescent in situ hybridization (egfr-FISH)

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Epidermal growth factor receptor gene polymorphisms are associated with prognostic features of breast cancer

Cited by 13 publications

References 41 publications

Chemokine axes in breast cancer: factors of the tumor microenvironment reshape the CCR7-driven metastatic spread of luminal-A breast tumors

Chemokine axes in breast cancer: factors of the tumor microenvironment reshape the CCR7-driven metastatic spread of luminal-A breast tumors

Q787Q EGFR Polymorphism as a Prognostic Factor for Lung Squamous Cell Carcinoma

Molecular genetic alterations in egfr CA-SSR-1 microsatellite and egfr copy number changes are associated with aggressiveness in thymoma

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