c-Kit expression as a prognostic molecular marker in patients with basal-like breast cancer

Kashiwagi, Shinichiro; Yashiro, Masakazu; Takashima, Tsutomu; Aomatsu, Naoki; Kawajiri, Hidemi; Ogawa, Yoshinari; Onoda, Naoyoshi; Ishikawa, Tetsuro; Wakasa, Kenichi; Hirakawa, Kosei

doi:10.1002/bjs.9021

Cited by 43 publications

(46 citation statements)

References 30 publications

(46 reference statements)

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“…Immunohistochemical studies were performed as previously described on core needle biopsy specimens [18, 19]. Tumor specimens were fixed in 10% formaldehyde solution and embedded in paraffin, and 4-μm-thick sections were mounted on glass slides.…”

Section: Methodsmentioning

confidence: 99%

Circulating tumor cell clusters-associated gene plakoglobin is a significant prognostic predictor in patients with breast cancer

et al. 2017

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BackgroundCirculating tumor cells (CTCs) are linked to metastatic relapse and are regarded as a prognostic marker for human cancer. High expression of plakoglobin, a cell adhesion protein, within the primary tumor is positively associated with CTC clusters in breast cancer. In this study, we investigated the correlation between plakoglobin expression and survival of breast cancer.MethodsWe evaluated 121 breast cancer patients treated with neoadjuvant chemotherapy. Expression of plakoglobin was identified by immunohistochemical staining in the cell membrane. We also examined the relation between the expression of plakoglobin and E-cadherin, an epithelial–mesenchymal transition (EMT) marker.ResultsPatients with high plakoglobin expression had significantly worse distant-metastasis-free survival (DMFS) (P = 0.016, log rank). Plakoglobin expression had no correlation with pathological complete response rate (P = 0.627). On univariate analysis with respect to distant metastasis, high plakoglobin expression showed worse prognosis than low plakoglobin expression [P = 0.036, hazard ratio (HR) = 3.719]. Multivariate analysis found the same result (P = 0.013, HR = 5.052). In addition, there was a significant relationship between the expression of plakoglobin and E-cadherin (P = 0.023).ConclusionsPlakoglobin expression is an independent prognostic factor in patients with breast cancer, particularly for DMFS, and this is related to EMT.Electronic supplementary materialThe online version of this article (doi:10.1186/s40364-017-0099-2) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Circulating tumor cell clusters-associated gene plakoglobin is a significant prognostic predictor in patients with breast cancer

et al. 2017

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“…Previous studies have shown varying results; Nielsen et al , 2004 reported no difference in survival for c-KIT positive BLBC patients compared to control [40], whereas Kashiwagi et al , 2012 found a poorer outcome for c-KIT positive BLBC patients with a hazard ratio of 2.29 [26]. One explanation for these opposing results is differences in cut-point for categorizing a sample as positive; Nielsen et al , 2004 used ≥25% stained cells as cut-point while Kashiwagi et al , 2012 set their limit to ≥10%.…”

Section: Discussionmentioning

confidence: 99%

The Three Receptor Tyrosine Kinases c-KIT, VEGFR2 and PDGFRα, Closely Spaced at 4q12, Show Increased Protein Expression in Triple-Negative Breast Cancer

et al. 2014

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BackgroundTriple-negative breast cancer (TNBC) is a heterogeneous subgroup of breast cancer with poor prognosis and no targeted therapy available. Receptor tyrosine kinases (RTKs) are emerging targets in anticancer therapy and many RTK-inhibiting drugs are currently being developed. The aim of this study was to elucidate if there is a correlation between the protein expression of three RTKs c-KIT, VEGFR2 and PDGFRα, their gene copy number, and prognosis in TNBC compared to non-TNBC.MethodsTumor tissue samples from patients diagnosed with primary breast cancer were stained with immunohistochemistry (IHC) for protein assessment, and with fluorescence in situ hybridization (FISH) for gene copy number determination. Breast cancer mortality (BCM), measured from the date of surgery to death, was used as endpoint.ResultsThe cohort included 464 patients, out of which 34 (7.3%) had a TNBC. High expression of the three RTKs was more common in TNBC compared to non-TNBC: c-KIT 49% vs. 10% (P<0.001), PDGFRα 32% vs. 19% (P = 0.07) and VEGFR2 32% vs. 6% (P<0.001). The odds ratio (OR) of c-KIT, VEGFR2 and PDGFRα positivity, adjusted for tumor characteristics, was 6.8, 3.6 and 1.3 times higher for TNBC than for non-TNBC. 73.5% of the TNBC had high expression of at least one of the three investigated receptors, compared to 30.0% of the non-TNBC (P<0.001). Survival analysis showed no significant difference in BCM for TNBC patients with high vs. low c-KIT, PDGFRα or VEGFR2 protein expression. 193 (42%) tumors were evaluated with FISH. No correlation was seen between increased gene copy number and TNBC, or between increased gene copy number and high protein expression of the RTK.Conclusionc-KIT, VEGFR2 and PDGFRα show higher protein expression in TNBC compared to non-TNBC. Further investigation clarifying the importance of these RTKs in TNBC is encouraged, as they are possible targets for anticancer therapy.

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“…The 93 primary tumors and the metastatic lesions in the lymph nodes from 57 patients were immunohistochemically stained as described previously (28). Briefly, the specimens were fixed in 10% formaldehyde solution and embedded in paraffin.…”

Section: Patientsmentioning

confidence: 99%

E-cadherin expression and cell proliferation in the primary tumor and metastatic lymph nodes of papillary thyroid microcarcinoma

Nakamura

Onoda

Noda

et al. 2013

Molecular and Clinical Oncology

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Abstract. Although papillary thyroid microcarcinoma (PTMC) has an excellent prognosis, certain cases exhibit aggressive clinical manifestations. In this study, we assessed the expression of E-cadherin and Ki-67 in primary PTMC tumors and metastatic lymph nodes, in order to investigate the mechanism underlying the mainly indolent but potentially malignant nature of PTMC. A total of 93 PTMC patients treated in our institute were included in this study. All primary tumors and 57 metastatic lymph nodes were immunohistochemically stained and a total of 73 tumors (78.5%) were positive for E-cadherin. E-cadherin expression was significantly less common at the invasive front (58.1%, P<0.01) compared to that at the center of the tumor. Tumors that had lost E-cadherin expression at the invasive front frequently presented with lymph node metastasis (70.6%). Small tumors (≤5 mm diameter) expressed E-cadherin significantly more frequently compared with larger tumors (P=0.04); however, no other particular characteristic was found to correlate with the status of E-cadherin expression in the primary tumors. E-cadherin expression was detected in 49 (86.0%) of the 57 metastatic foci and correlated significantly with the expression status at the invasive front of the tumor (P=0.02). The Ki-67 index was universally low and was not correlated with the clinicopathological characteristics or the E-cadherin expression of the tumors. These results suggested that cancer cells in the metastatic lymph nodes exhibit indolent characteristics, similar to those of the primary PTMC. However, the metastatic cancer cells may have already completed the process of epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET), suggesting an innate malignant potential. IntroductionAccording to the World Health Organization classification system for thyroid tumors, papillary thyroid microcarcinoma (PTMC) is defined as a papillary thyroid carcinoma (PTC) measuring ≤10 mm in its greatest dimension (1). The occurrence of PTMC is on the increase worldwide (2-4), along with the frequent application of neck ultrasonography (US) (5,6). PTMC is generally characterized by an indolent clinical course and has an excellent prognosis, with a disease-specific mortality of <0.5% (6). However, certain PTMC cases were found to be clinically aggressive (6,7). According to the observations of Sugitani et al (7), PTMC patients with bulky lymph node metastases or extrathyroidal invasion were at the highest risk for a cancer-specific fatal outcome. Those observations suggested that there is a group of PTMCs that have already acquired highly malignant potential. However, the basic mechanism underlying the development of aggressive characteristics in these tumors has not yet been identified.The reported risk factors for PTMC recurrence were shown to be male gender (8,9), extent of primary surgery (10), presence of lymph node metastases at initial diagnosis (3,(8)(9)(10)(11)(12), tumor multifocality (3,8,12) and capsular invasion (9,(11)(12)(13)(14...

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c-Kit expression as a prognostic molecular marker in patients with basal-like breast cancer

Abstract: c-Kit might be a prognostic marker and possible molecular target for therapy in patients with BLBC.

Cited by 43 publications

References 30 publications

Circulating tumor cell clusters-associated gene plakoglobin is a significant prognostic predictor in patients with breast cancer

Circulating tumor cell clusters-associated gene plakoglobin is a significant prognostic predictor in patients with breast cancer

The Three Receptor Tyrosine Kinases c-KIT, VEGFR2 and PDGFRα, Closely Spaced at 4q12, Show Increased Protein Expression in Triple-Negative Breast Cancer

E-cadherin expression and cell proliferation in the primary tumor and metastatic lymph nodes of papillary thyroid microcarcinoma

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