Robinson Cytologic Grading in Invasive Ductal Carcinoma of the Breast

Robles-Frías, Antonio; González‐Cámpora, Ricardo; Martínez-Parra, Diego; Robles‐Frías, María José; Vázquez-Cerezuela, Teresa; Otal-Salaverri, C; González, C. Almeida

doi:10.1159/000325924

Cited by 5 publications

(2 citation statements)

References 23 publications

(19 reference statements)

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“…Many studies have shown a correlation between reduced e-cadherin expression and increased metastasis both in laboratory models and in clinical samples; however, a direct functional role of γ-catenin in this process has not been shown [29-33]. Evidence from clinical studies suggests that reduced expression of plakoglobin in human breast cancers is associated with increased tumor progression and adverse clinical outcome [34-36]. Additionally, translocation of γ-catenin from the membrane to the cytoplasm has been shown in breast cancers with a more-aggressive phenotype [37].…”

Section: Discussionmentioning

confidence: 99%

Loss of plakoglobin promotes decreased cell-cell contact, increased invasion, and breast cancer cell dissemination in vivo

et al. 2012

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IntroductionThe majority of deaths from breast cancer are a result of metastases; however, little is understood about the genetic alterations underlying their onset. Genetic profiling has identified the adhesion molecule plakoglobin as being three-fold reduced in expression in primary breast tumors that have metastasized compared with nonmetastatic tumors. In this study, we demonstrate a functional role for plakoglobin in the shedding of tumor cells from the primary site into the circulation.MethodsWe investigated the effects of plakoglobin knockdown on breast cancer cell proliferation, migration, adhesion, and invasion in vitro and on tumor growth and intravasation in vivo. MCF7 and T47D cells were stably transfected with miRNA sequences targeting the plakoglobin gene, or scramble vector. Gene and protein expression was monitored by quantitative polymerase chain reaction (qPCR) and Western blot. Cell proliferation, adhesion, migration, and invasion were measured by cell counting, flow cytometry, and scratch and Boyden Chamber assays. For in vivo experiments, plakoglobin knockdown and control cells were inoculated into mammary fat pads of mice, and tumor growth, shedding of tumor cells into the bloodstream, and evidence of metastatic bone lesions were monitored with caliper measurement, flow cytometry, and microcomputed tomography (μCT), respectively.ResultsPlakoglobin and γ-catenin expression were reduced by more than 80% in all knockdown cell lines used but were unaltered after transfection with the scrambled sequence. Reduced plakoglobin resulted in significantly increased in MCF7 and T47D cell proliferation in vitro and in vivo, compared with control, with significantly more tumor cells being shed into the bloodstream of mice bearing plakoglobin knockdown tumors. In addition, plakoglobin knockdown cells showed a >250% increase in invasion through basement membrane and exhibited reduced cell-to-cell adhesion compared with control cells.ConclusionDecreased plakoglobin expression increases the invasive behavior of breast cancer cells. This is the first demonstration of a functional role for plakoglobin/γ-catenin in the metastatic process, indicating that this molecule may represent a target for antimetastatic therapies.

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Section: Discussionmentioning

confidence: 99%

Loss of plakoglobin promotes decreased cell-cell contact, increased invasion, and breast cancer cell dissemination in vivo

et al. 2012

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“…[1617] Robles-Frias et al ,[18] also found a statistically significant association between cytologic and histologic grades ( P < 0.0005) and between cytologic grade and presence of axillary metastasis ( P < 0.0005). In their further study Robles-Frias et al ,[19] found a statistically significant correlation between E-Cadherin/Catenin expression and cytologic grade ( P < 0.0005) and this association was particularly relevant to cell dissociation parameter ( P < 0.0005). Similar results were observed here, testifying to the striking potential of this correlation.…”

Section: Discussionmentioning

confidence: 90%

Role of cytologic grading in prognostication of invasive breast carcinoma

Khan

Afroz

Rana

et al. 2009

J Cytol

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Background:Evaluation of cytologic features is indispensable in the preoperative diagnosis and grading of infiltrating ductal breast carcinoma (CA) in fine-needle aspiration cytology (FNAC) material and this method can also provide additional information regarding intrinsic features of the tumor as well as its prognosis.Aim:This study has been done to evaluate comparatively the cytologic and histomorphologic grading of infiltrating ductal carcinoma of breast with specific reference to lymph node metastasis and its role in prognostication.Materials and Methods:Forty three patients who underwent FNAC and mastectomy for infiltrating ductal carcinoma were cytologically and histologically graded (employing Robinson's cytologic grading system and Elston's modification of Bloom-Richardson system, respectively). Statistical analysis was done employing ‘z’ test and χ2 test to compare the two grading system and to examine the degree of correlation between the cytologic and histologic grades. Multiple regression analysis was done to assess the significance of every cytologic and histologic parameter. All 43 cases, graded cyto-histologically were also evaluated for presence or absence of metastasis to the regional lymph nodes employing χ2 test.Results:With histologic grade taken as the standard, cytology was found to be fairly comparable, for grading breast carcinoma (overall sensitivity 89.1%, specificity 100%). Further comparison of the two grading systems by Z-test showed that difference between the cytologic and histologic grading was insignificant in all the three grade (P > 0.05). Of the six parameters studied, cell dissociation, nucleoli and chromatin pattern were the most influential features (P < 0.001). The statistically significant difference (p < 0.001) was found in incidences of axillary lymph node metastatic rate in three cytologic grades (15.4% in grade I vs. 83.3% in grade III) as well.Conclusions:Apart from being simple and noninvasive, cytologic grading is comparable to histologic grading and might provide relevant information on the aggressiveness of invasive ductal carcinoma of breast and could be a useful parameter to take into consideration when selecting mode of therapy and to predict tumor behavior.

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Bench to bedside and back again: Molecular mechanisms of α-catenin function and roles in tumorigenesis

Benjamin

Nelson

2008

Seminars in Cancer Biology

106

115

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The cadherin/catenin complex, comprised of E-cadherin, β-catenin and α-catenin, is essential for initiating cell-cell adhesion, establishing cellular polarity and maintaining tissue organization. Disruption or loss of the cadherin/catenin complex is common in cancer. As the primary cell-cell adhesion protein in epithelial cells, E-cadherin has long been studied in cancer progression. Similarly, additional roles for β-catenin in the Wnt signaling pathway has led to many studies of the role of β-catenin in cancer. Alpha-catenin, in contrast, has received less attention. However, recent data demonstrate novel functions for α-catenin in regulating the actin cytoskeleton and cell-cell adhesion, which when perturbed could contribute to cancer progression. In this review, we use cancer data to evaluate molecular models of α-catenin function, from the canonical role of α-catenin in cell-cell adhesion to non-canonical roles identified following conditional α-catenin deletion. This analysis identifies α-catenin as a prognostic factor in cancer progression.

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Robinson Cytologic Grading in Invasive Ductal Carcinoma of the Breast

Cited by 5 publications

References 23 publications

Loss of plakoglobin promotes decreased cell-cell contact, increased invasion, and breast cancer cell dissemination in vivo

Loss of plakoglobin promotes decreased cell-cell contact, increased invasion, and breast cancer cell dissemination in vivo

Role of cytologic grading in prognostication of invasive breast carcinoma

Bench to bedside and back again: Molecular mechanisms of α-catenin function and roles in tumorigenesis

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