Microvessel proliferation by co-expression of endothelial nestin and Ki-67 is associated with a basal-like phenotype and aggressive features in breast cancer.

BACKGROUND: To quantify tumour angiogenesis, microvessel density (MVD) has been widely used. We here present a novel angiogenesis marker, microvessel proliferation (MVP), based on dual immunohistochemical staining of nestin and Ki-67. Immature endothelial cells express nestin, and when co-expressed with the proliferation marker Ki-67, the number of proliferating immature blood vessels can be measured. MATERIALS AND METHODS: Microvessel proliferation was evaluated in 178 breast cancer samples and estimated by vascular proliferation index (VPI), the ratio between the number of vessels containing proliferating endothelial cells and the total number of immature vessels. RESULTS: High VPI was strongly associated with several markers of aggressive breast cancer, such as negative oestrogen receptor (ER) status (p = 0.003), high tumour cell proliferation by Ki-67 (p = 0.004), high p53 expression (p = 0.001), and five profiles for the basal-like phenotype (odds ratios (OR); range 3.4-6.3). Also, high VPI was significantly associated with interval detected breast cancer compared with screening detected lesions (p < 0.0005), and adverse outcome in univariate and multivariate survival analysis (p = 0.034 and p = 0.022, respectively). CONCLUSION: Microvessel proliferation is a novel marker of ongoing angiogenesis and was associated with aggressive tumour features, basal-like phenotypes, interval presentation, and prognosis in this series of breast cancer.

Expression of aldehyde dehydrogenase 1 (ALDH1) is associated with basal-like markers and features of aggressive tumours in African breast cancer.

BACKGROUND: Putative breast cancer stem cells might express surface markers such as aldehyde dehydrogenase 1 (ALDH1) and BMI-1 proteins. The aim of this study was to explore the expression of these proteins in breast cancers from an African population and their associations with the basal-like phenotype (BLP) and other molecular characteristics. METHODS: We analysed 192 paraffin-embedded breast carcinoma samples by tissue microarrays and immunohistochemical methods. RESULTS: In total, 88 tumours (48%) expressed ALDH1, whereas 46 (25%) expressed BMI-1 protein. Expression of ALDH1 was associated with high histological grade (P<0.0005), high mitotic count (P<0.0005), high nuclear grade (P<0.0005), oestrogen receptor (ER) negativity (P<0.0005), progesterone receptor (PR) negativity (P=0.009), p53 expression (P=0.034), cytokeratin 5/6 positivity (P=0.008), epidermal growth factor receptor (EGFR) expression (P=0.015) and the BLP (P<0.0005), whereas it was inversely associated with BMI-1 staining (P=0.009). On the other hand, BMI-1 expression was associated with low histological grade (P=0.004) and ER positivity (P=0.001). CONCLUSION: There was a high prevalence of ALDH1 expression among breast carcinomas and associations with basal markers and features of aggressive tumours. Studies are required to elucidate the importance of these findings for improved understanding of breast cancer biology.

Expression of epidermal growth factor receptor in relation to BRCA1 status, basal-like markers and prognosis in breast cancer.

AIMS: BRCA1-related breast cancer is associated with a basal-like phenotype, and is frequently oestrogen receptor (ER) and HER2 negative. The expression of epidermal growth factor receptor (EGFR) has been considered to be one component of the basal-like phenotype, but no standard criteria exist. This study investigates the relationship between EGFR expression, BRCA1 status and basal markers with respect to clinicopathological associations and prognosis, in addition to evaluating different criteria for EGFR assessment by immunohistochemistry. METHODS: A tissue microarray comprising 230 available cases, from a series of primary invasive breast cancer diagnosed in Ashkenazi Jewish women during 1980-1995, was stained for EGFR using the Dako PharmDX kit, and evaluated by Webslide virtual microscopy. RESULTS: EGFR was positive in 9-19% according to different criteria. Expression was associated with BRCA1 carrier status and basal-like markers as negative ER, positive cytokeratin 5/6 and positive P-cadherin staining. EGFR was prognostically significant by univariate and multivariate analysis within the group carrying germ-line BRCA1 mutations. Histological grade, axillary lymph node status and P-cadherin status had significant independent value in the final multivariate model including all cases, whereas EGFR was not significant in this model. All five scoring systems gave comparable results concerning clinicopathological associations and patient outcome, although the most restrictive criteria (EGFR-HI) tended to be most sensitive in predicting BRCA1 status, a basal phenotype, and patient prognosis. CONCLUSIONS: EGFR expression, being present in 9-19% of the cases, was prognostically significant among BRCA1 mutated cases only. In multivariate survival analysis of all cases, no independent effect was seen. However, EGFR immunostaining might be relevant to predict the response to targeted therapy, and this should be studied further.

Independent prognostic value of the basal-like phenotype of breast cancer and associations with EGFR and candidate stem cell marker BMI-1.

AIMS: To study the relationship between basal-like breast cancers, epidermal growth factor receptor (EGFR) and candidate stem cell markers (BMI-1, EZH2, Oct-4) in a population-based setting. METHODS AND RESULTS: Immunohistochemistry was evaluated in a series of 190 breast cancers. Basal-like phenotype (BLP) 1-5 was found in 4.3-14.3% of cases. EGFR was expressed in 9% of cases and associated with cytokeratin (CK) 5 and P-cadherin positivity, but not with survival; 28% of CK5+ cases were EGFR+. On multivariate analysis, basal-like differentiation and lymph node status were independent prognostic factors of comparable strength. BMI-1 positivity (42.6%) was associated with absence of basal-like features, oestrogen receptor positivity and low Ki67, but not related to survival. BMI was not associated with EZH2 expression, and these markers tended to show opposite associations with other variables, suggesting different roles in breast cancer. Oct-4 expression was not detected in this series. CONCLUSIONS: Basal-like features and lymph node status were strong and independent prognostic factors in this population-based series of breast cancer. Neither EGFR nor BMI-1 had significant prognostic impact, whereas EZH2 expression was associated with decreased survival. BMI-1 was inversely related to basal-like factors, and a stem cell phenotype of the basal-like subgroup could not be verified by this marker.

[Orbital tumors]. / Svulster i orbita.

BACKGROUND: Orbital tumours are relatively uncommon, and few series of patients with such tumours have been reported from Scandinavia. Here we present the experience of a Norwegian referral centre. MATERIAL AND METHODS: We have retrospectively evaluated the records of 278 patients with orbital tumours hospitalized at the Department of Ophthalmology, Haukeland University Hospital from 1961 to 1999. RESULTS: In 177 patients, a benign tumour was present, while 96 patients suffered from malignant disease. In five cases, the malignant potential of the tumour could not be assessed. A total of 71 different histological entities were observed. Surgical treatment performed at our department was in 22 patients exenteration, in 87 lateral orbitotomy, in 47 anterior orbitotomy and in 41 biopsy through an anterior approach. INTERPRETATION: This series illustrates the wide panorama of space-occupying lesions that may be present in the orbit. Since the lesions are rare and management in many cases complex, the treatment should be centralized to an eye department with a defined interest in orbital disease.