Vimentin and p53 expression on epidermal growth factor receptor-positive, oestrogen receptor-negative breast carcinomas

Cattoretti, Giorgio; Andreola, Salvatore; Clemente, Claudio; D'Amato, Lucia; Rilke, F

doi:10.1038/bjc.1988.81

Cited by 81 publications

(33 citation statements)

References 27 publications

(27 reference statements)

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“…[23][24][25][26][27] Previous studies have shown an association between tumor vimentin expression, a poor prognosis, and ERnegative status. 23,24 Cattoretti et al 23 described a group of ER-negative tumors that often showed coexpression of vimentin, p53 and EGFR, which is a phenotype that is very consistent with the basallike subtype currently described. We have shown here and before that many basal-like tumors are EGFR þ , and Sorlie et al 2 showed that most basallike tumors are p53 mutated.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma

et al. 2006

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Microarray profiling of invasive breast carcinomas has identified five distinct subtypes of tumors (luminal A, luminal B, normal breast-like, HER2 overexpressing, and basal-like) that are associated with different clinical outcomes. The basal-like subtype is associated with poor clinical outcomes and is the subtype observed in BRCA1-related breast cancers. The aim of this study was to characterize the histologic and immunophenotypic properties of breast basal-like carcinomas that were first positively identified using DNA microarray analysis. Detailed histologic review was performed on 56 tumors with known microarray profiles (23 basal-like, 23 luminal, and 12 HER2 þ ). Immunohistochemistry for estrogen receptor (ER), HER2, EGFR, smooth muscle actin (SMA), p63, CD10, cytokeratin 5/6, cytokeratin 8/18, and vimentin was performed on 18 basal-like, 16 luminal, and 12 HER2 þ tumors. The basal-like tumors were grade 3 ductal/NOS (21/23) or metaplastic (2/23) carcinomas that frequently showed geographic necrosis (17/23), a pushing border of invasion (14/23), and a stromal lymphocytic response (13/23). Most basal-like tumors showed immunoreactivity for vimentin (17/18), luminal cytokeratin 8/18 (15/18), EGFR (13/18), and cytokeratin 5/6 (11/18), while positivity for the myoepithelial markers SMA (4/18), p63 (4/18) and CD10 (2/18) was infrequent. All basal-like tumors tested were ERÀ and HER2À. Morphologic features significantly associated with the basal-like subtype included markedly elevated mitotic count (Po0.0001), geographic tumor necrosis (P ¼ 0.0003), pushing margin of invasion (P ¼ 0.0001), and stromal lymphocytic response (P ¼ 0.01). The most consistent immunophenotype seen in the basal-like tumors was negativity for ER and HER2, and positivity for vimentin, EGFR, cytokeratin 8/18, and cytokeratin 5/6. The infrequent expression of myoepithelial markers in basal-like carcinomas does not support a direct myoepithelial cell derivation of these tumors. These findings should further assist in the identification of basal-like carcinomas in clinical specimens, facilitating treatment and epidemiologic studies of this tumor subtype.

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Section: Discussionmentioning

confidence: 99%

Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma

et al. 2006

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“…It appears that some reports have previously described the morphologic aspects of basal-like carcinomas before the gene expression profiling experiments. [13][14][15][16] It has been known for several years that myoepithelial and luminal epithelial cells have different In order to validate the characteristic immunohistologic findings and to identify any precursor lesion of basal-like carcinomas, we searched our pathology database for breast carcinomas in women less than 37 years of age. This was performed simply to increase the yield of high-grade, ER-negative breast carcinomas, as these are more common in the younger age group.…”

Section: Discussionmentioning

confidence: 99%

Basal phenotype of ductal carcinoma in situ: recognition and immunohistologic profile

et al. 2006

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The basal phenotype of breast carcinoma was demonstrated from a study of gene expression profiles, which demonstrated five carcinoma phenotypes with differing immunohistologic profiles and outcomes. The basal phenotype, so-named because of an immunohistologic profile that is similar to myoepithelial cells of the breast, has poor outcomes. While the invasive basal phenotype has been described, there is a paucity of literature regarding the existence or recognition of a precursor lesion. We searched our CoPath database for breast carcinomas in the age group of 37 years or less, and this yielded 98 cases from the years 2001 to April 2006. Pathology reports were screened for those cases that were negative for estrogen and progesterone receptors and HER-2/neu (triple negative). A total of 16 cases (16/98, 16%) fulfilled these criteria. Histology was reviewed and immunostains were performed for Cytokeratins 14, 17, and 5/6, vimentin, EGFR, c-kit, smooth muscle actin and p63. All 16 cases had a high-grade invasive ductal carcinoma, Nottingham score 9/9, with geographic necrosis, good circumscription and lymphoid infiltrates. Of the 16 cases, 13 exhibited at least one area of ductal carcinoma in situ (DCIS). The DCIS types were solid, flat or micropapillary, high nuclear grade, with comedonecrosis and invariably associated with intense lymphoid inflammatory cell infiltration. Of 16 invasive cases, 14 (88%) were positive for CK14, CK17, CK5/6 and EGFR; 94% were vimentin positive, while half or less of cases were positive for smooth muscle actin, c-kit or p63. All of the DCIS components demonstrated the same immunohistologic profile as the invasive component. A DCIS component of solid, flat or micropapillary type exists in the basal phenotype of breast carcinoma, and it demonstrates the same immunophenotype as the invasive carcinoma, typically positive for CK5/6, CK14, CK17, vimentin and EGFR, but negative for ER/PR and HER-2/neu.

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“…IGFBP5 is also down-regulated by estrogen and up-regulated by the pure anti-estrogen fulvestrant (faslodex, ICI 182,780), and because a targeted antisense to IGFBP5 can inhibit the growth effects of estrogen and anti-estrogens, it has been proposed to play a role in the modulation of proliferation (32). Vimentin expression is frequently inversely associated with ER expression in breast cancers (33,34), and we had found it to be 3-fold down-regulated by E 2 in our ovarian cancer model (35). These proteins require further testing in a prospective cohort of patients but could potentially be used to predict letrozole sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Antiestrogen Therapy Is Active in Selected Ovarian Cancer Cases: The Use of Letrozole in Estrogen Receptor–Positive Patients

Smyth

Gourley

Walker

et al. 2007

Clinical Cancer Research

168

138

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Purpose: To evaluate the efficacy of the aromatase inhibitor letrozole in preselected estrogen receptor (ER)^positive relapsed epithelial ovarian cancer patients and to identify markers that predict endocrine-sensitive disease. Experimental Design: This was a phase II study of letrozole 2.5 mg daily until clinical or marker evidence of disease progression in previously treated ER-positive ovarian cancer patients with a rising CA125 that had progressed according to Rustin's criteria. The primary end point was response according to CA125 and response evaluation criteria in solid tumors (RECIST) criteria. Marker expression was measured by semiquantitative immunohistochemistry in sections from the primary tumor. Results: Of 42 patients evaluable for CA125 response, 7 (17%) had a response (decrease of >50%), and 11 (26%) patients had not progressed (doubling of CA125) following 6 months on treatment. The median time taken to achieve the CA125 nadir was 13 weeks (range 10-36). Of 33 patients evaluable for radiological response, 3 (9%) had a partial remission, and 14 (42%) had stable disease at 12 weeks. Eleven patients (26%) had a PFS of >6 months. Subgroup analysis according to ER revealed CA125 response rates of 0% (immunoscore, 150-199), 12% (200-249), and 33% (250-300); P = 0.028, m 2 for trend. Expression levels of HER2, insulin-like growth factor binding protein 5, trefoil factor 1, and vimentin were associated with CA125 changes on treatment. Conclusions: This is the first study of a hormonal agent in a preselected group of ER-positive ovarian cancer patients. A signature of predictive markers, including low HER2 expression, predicts response.

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Vimentin and p53 expression on epidermal growth factor receptor-positive, oestrogen receptor-negative breast carcinomas

Cited by 81 publications

References 27 publications

Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma

Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma

Basal phenotype of ductal carcinoma in situ: recognition and immunohistologic profile

Antiestrogen Therapy Is Active in Selected Ovarian Cancer Cases: The Use of Letrozole in Estrogen Receptor–Positive Patients

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