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PubMed2006

CD44v3 levels in primary cutaneous melanoma are predictive of prognosis: assessment by the use of tissue microarray.

Despite the use of sentinel node biopsy techniques, the search continues for other strategies to improve the accuracy of estimating prognosis in melanoma patients. Various biomarkers have previously been studied for use in this role, but none has yet achieved acceptance in routine practice. We have applied the novel technology of tissue microarray for the high throughput screening of a cohort of 120 primary cutaneous melanoma specimens for expression of the transmembrane glycoprotein CD44, splice variant 3 (v3), which has previously been implicated in tumor progression. A highly significant correlation between CD44v3 expression and Breslow thickness, Clark's level and patient age was demonstrated (Spearman correlation p < 0.001). Regarding clinical outcome, CD44v3 expression was shown to be significantly associated with better outcome (chi(2) = 7.2219, p = 0.0072). Furthermore, subgroup analysis revealed a sequentially improved survival probability associated with the intensity of CD44v3 staining (chi(2) = 12.5162, p = 0.0058). Analysis in a Cox multivariate model, however, did not show CD44v3 to be independently predictive of prognosis. The implications of these findings are considered, and the use of CD44v3 as a potential prognostic marker or a target for therapeutic manipulation are discussed.

Adult↗

PubMed2005

The role of CXCR4 receptor expression in breast cancer: a large tissue microarray study.

The chemokine receptor CXCR4 is an important factor in the migration, invasiveness, metastasis and proliferation of breast cancer cells. We have retrospectively analyzed the levels of expression of CXCR4 in a large cohort of breast cancers and pre-invasive breast samples linked to clinical data. A total of 1808 invasive breast carcinomas and 214 pre-invasive breast samples could be analyzed in correlation with basic clinico-pathological data such as hormone receptor status, HER2 status and tumor grade. The majority of breast cancers expressed either nuclear or cytoplasmic staining or both. CXCR4 cytoplasmic expression was associated with parameters of tumor aggressivity (tumor grade and lymph node status) and had prognostic value (age-adjusted hazard ratio=1.73; Confidence Interval: 1.07-2.77) with respect to disease-specific survival. CXCR4 positivity in the cytoplasm but not the nucleus was associated with HER2 expression and amplification as well as with hormone receptor negativity (both ER and PR). The percentage of nuclear staining increased from normal breast tissue (20%) to ductal carcinoma-in-situ DCIS (43%) to invasive cancer (67%) while CXCR4 was expressed in the cytoplasm of 67% of (DCIS) cases (double that in normal breast samples), suggesting an important role in breast tumor progression. The CXCR4 receptor is expressed in many breast cancers, justifying its development as a therapeutic target in breast cancer patients. Its cytoplasmic expression is associated with breast tumor progression, suggesting potential value as a diagnostic marker.

Adult↗

PubMed2005

Distribution of AQP2 and AQP3 water channels in human tissue microarrays.

The objective of this investigation was to use semi-quantitative immunohistochemistry to determine the distribution and expression levels of AQP2 and AQP3 proteins in normal human Tissue MicroArrays. Expression of the vasopressin regulated AQP2 was observed in a limited number of tissues. AQP2 was prominent in the apical and subapical plasma membranes of cortical and medullary renal collecting ducts. Surprisingly, weak AQP2 immunoreactivity was also noted in pancreatic islets, fallopian tubes and peripheral nerves. AQP2 was also localized to selected parts of the central nervous system (ependymal cell layer, subcortical white matter, hippocampus, spinal cord) and selected cells in the gastrointestinal system (antral and oxyntic gastric mucosa, small intestine and colon). These findings corroborate the restricted tissue distribution of AQP2. AQP3 was strongly expressed in many of the human tissues examined particularly in basolateral membranes of the distal nephron (medullary collecting ducts), distal colon, upper airway epithelia, transitional epithelium of the urinary bladder, tracheal, bronchial and nasopharyngeal epithelium, stratified squamous epithelial cells of the esophagus, and anus. AQP3 was moderately expressed in basolateral membranes of prostatic tubuloalveolar epithelium, pancreatic ducts, uterine endometrium, choroid plexus, articular chondrocytes, subchondral osteoblasts and synovium. Low AQP3 levels were also detected in skeletal muscle, cardiac muscle, gastric pits, seminiferous tubules, lymphoid vessels, salivary and endocrine glands, amniotic membranes, placenta and ovary. The abundance of basolateral AQP3 in epithelial tissues and its expression in many non-epithelial cells suggests that this aquaglyceroporin is a major participant in barrier hydration and water and osmolyte homeostasis in the human body.

Aquaporin 2↗

PubMed2006

Distribution of GDNF family receptor alpha3 and RET in rat and human non-neural tissues.

The neurotrophic growth factor artemin binds selectively to GDNF family receptor alpha3 (GFRalpha3), forming a molecular complex with the co-receptor RET which mediates downstream signaling. This signaling pathway has been demonstrated to play an important role in the survival and maintenance of nociceptive sensory neurons and in the development of sympathetic neurons. However, the presence and potential role of this artemin-responsive pathway in non-neural tissues has not been fully explored to-date. To study the distribution of GFRalpha3 and RET in adult rat and human non-neural tissues, we carried out a comprehensive immunohistochemical study. We stained major organs from the digestive, urinary, reproductive, immune, respiratory and endocrine systems, and from other systems (cardiovascular, skeletal muscle), as well as regions of the nervous system for comparison. In both rat and human, the majority of non-neural cells did not exhibit detectable GFRalpha3-like immunoreactivity. In the rat, GFRalpha3- and RET-like staining were found in the same non-neural cell type only in kidney. In the human digestive and reproductive systems, a subset of epithelial cells exhibited GFRalpha3- and RET-like staining, suggesting co-localization. In other tissues, sub-populations of cells expressed either GFRalpha3- or RET-like immunoreactivity. The functional consequences of GFRalpha3 expression in non-neural cells remain to be determined.

Adult↗

PubMed2005

Improved prognostication in soft tissue sarcoma: independent information from vascular invasion, necrosis, growth pattern, and immunostaining using whole-tumor sections and tissue microarrays.

In 140 mixed primary soft tissue sarcomas with a median follow-up of 6 years, the prognostic importance of tumor size, tumor depth, grade, necrosis, vascular invasion, and peripheral growth pattern (pushing versus infiltrating) was evaluated on whole-tumor sections. Immunohistochemical expression of Ki-67, p53, cyclin A, bcl-2, beta-catenin, CD44, and P-glycoprotein was determined using tissue microarray from the peripheral growth zone. Local recurrences developed in 17% of the patients and correlated with necrosis, vascular invasion, and cyclin A expression. No local recurrence developed in tumors with a pushing growth pattern, regardless of tumor grade and depth. Metastasis developed in 39% of the patients. Vascular invasion was identified in 36% of the tumors and was the strongest prognostic factor for metastasis with a hazard ratio of 3.5. Growth pattern and tumor necrosis were also strong prognostic factors for metastasis, whereas malignancy grade, tumor size, and tumor depth did not have any independent prognostic value. Immunostaining showed independent prognostic information for Ki-67, beta-catenin, CD44, and P-glycoprotein. The results indicate that whole-tumor sections could facilitate identification of vascular invasion, necrosis, and peripheral growth pattern and that immunohistochemical profiling from the growth zone also provides independent prognostic information for metastasis in soft tissue sarcoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Tissue microarrays from HOPE-fixed specimens allow for enhanced high throughput molecular analyses in paraffin-embedded material.

In this study, we describe a technique that allows for the production and the use of tissue microarrays (TMA) from HOPE-fixed, paraffin-embedded specimens. The combination of these two technologies unites the advantages of the high throughput aspects in TMA, with good preservation of nucleic acids, proteins, and morphology of HOPE-fixed tissues, thus substantially widening the capabilities presently available for molecular studies in paraffin-embedded tissues.

Biomarkers↗

PubMed2005

Estrogen receptor-negative breast carcinomas: a review of morphology and immunophenotypical analysis.

Estrogen receptor (ER)-negative breast cancers are a group of tumors with poor prognosis and fewer cancer prevention and treatment strategies compared to ER-positive tumors. The aim of this study was to assess the morphological characteristics and immunohistochemical profile of ER-negative tumors and thus to understand the biological behavior and unique nature. In total, 291 consecutive ER-negative cases available from our primary breast cancer series were examined. Hematoxylin- and eosin-stained sections of all the cases were studied for several morphological parameters and their immunophenotype profile. These findings were correlated with patient and tumor characteristics and survival data. ER-negative tumors constituted 30% of the primary operable breast cancer series. The majority of tumors were grade 3 (94%) and the commonest histological types were ductal/no specific type (85%), and atypical medullary carcinoma (8%). High-grade comedo-type necrosis, lymphoid stroma, central necrosis/fibrosis and pushing margins were the most common morphological features. The presence of a pushing margin showed a significant relation to androgen receptor negativity, absence of epidermal growth factor receptor expression and negative lymph nodes. Lymphoid stroma and comedo-necrosis correlated with higher tumor grade. ER-negative breast cancers are a distinct group of tumors with several common morphological features. Grade 3 histology, pushing margin, lymphoid stroma, comedo-type necrosis and central fibrosis/necrosis are the dominant morphological findings. The presence of a pushing margin appears to have a significant correlation with negative lymph node status. ER-negative tumors show a higher expression of p53, CerbB2 and epidermal growth factor receptor compared to ER-positive breast cancer. These unique features support the concept that ER-negative tumors are a morphologically and phenotypically distinct entity and provide a rationale for the study and use of newer promising agents in the treatment of ER-negative breast cancer.

Actins↗

PubMed2005

Claudin-1 is a strong prognostic indicator in stage II colonic cancer: a tissue microarray study.

Tight junction associated proteins are key molecular components governing cellular adhesion, polarity and glandular differentiation. Tight junction proteins also play critical roles in cellular proliferation and neoplastic pathways via their functions as couplers of the extracellular milieu to intracellular signaling pathways and the cytoskeleton. Neoplastic cells frequently exhibit structural and functional deficiencies in the tight junction. The purpose of this study was to determine the pattern of expression and prognostic value of four tight junction associated proteins, claudin-1, claudin-4, occludin and ZO-1 in a cohort of TNM stage II colon cancer using tissue microarray technology. In this study, we retrospectively analyzed, resected and otherwise untreated paraffin embedded specimens from 129 consecutive patients with TNM stage II colonic carcinomas for claudin-1, claudin-4, occludin and ZO-1 protein expression by immunohistochemistry. Seventy-five, 58, 56 and 44% of the tumors exhibited normal to elevated expression levels (+2 and +3 immunopositivity) of claudin-1, claudin-4, occludin and ZO-1 respectively. Low expression levels of claudin-1 and ZO-1 were directly associated with higher tumor grade (P=0.05 and 0.03 respectively). Multivariate analysis indicated that lymphovascular invasion (P=0.01) and low levels of claudin-1 (P=0.0001) expression were independent predictors of recurrence and that reduced claudin-1 expression (P=0.0001) was associated with poor survival. This study is the first to comprehensively examine the expression of several tight junction associated proteins in colonic neoplasms and to correlate their expression with disease progression. Loss of claudin-1 expression proved to be a strong predictor of disease recurrence and poor patient survival in stage II colon cancer.

Adult↗

PubMed2005

Overexpression and hyperphosphorylation of retinoblastoma protein in the progression of malignant melanoma.

Mutation, absence or abnormal functioning of retinoblastoma protein are fundamental elements of uncontrolled growth in human cancer. In this study, we analyze the expression of retinoblastoma protein and phosphorylated retinoblastoma protein in melanocytic tumors in vivo. Real-time RT-PCR and immunohistochemistry (tissue microarrays and conventional histological sections) reveal that retinoblastoma protein is progressively upregulated in advanced and metastatic malignant melanomas in vivo. However, this increase is paralleled by increased retinoblastoma protein inactivation due to protein phosphorylation. Interestingly, retinoblastoma protein phosphorylation occurs not homogeneously, but with a 'growth zone'-related pattern. In superficial spreading melanomas a subepidermal-lateral maximum of phosphorylated retinoblastoma protein can be frequently observed. Accordingly, nodular vertically invasive melanomas are characterized by a strong staining of phosphorylated retinoblastoma protein in deep-dermal invading protrusions of the tumor. Furthermore, Kaplan-Meier analysis of 13 cases of advanced melanomas with long-time follow-up suggests a significant negative impact of retinoblastoma protein phosphorylation on survival of melanoma patients independent of tumor thickness. We conclude that the evaluation of phosphorylated retinoblastoma protein in melanocytic tumors could become a helpful adjunct in clinicopathological routine.

Disease Progression↗

PubMed2006

MDM2 protein expression is a negative prognostic marker in breast carcinoma.

The protein encoded by the MDM2 oncogene inhibits the function of p53, leading to increased cell growth, avoidance of apoptosis, tolerance of genetic instability, and resistance to chemotherapy. The present study was performed to evaluate the relationship between MDM2 protein expression and survival in breast carcinoma. Two series of cases were used in this study: the first to identify the cutoff to be used in the interpretation of MDM2 immunostaining and perform preliminary survival analysis, and a second, independent series, to validate the findings from the first series and to perform multivariate analysis. For both series, archival sections of tissue microarrays were stained with anti-MDM2 antibody (NeoMarkers, Fremont, CA, USA) and MDM2 staining intensity was scored semiquantitatively. In the first series, 49 of 362 (14%) interpretable cases were positive for MDM2 expression, with 35 (10%) showing weak positivity and 14 (4%) strong positivity. Patients with MDM2-positive tumours had a significantly worse disease-specific survival than patients with MDM2-negative tumours (P=0.0022, 10-year DSS 61% (95% CI: 45-73) vs 73% (95% CI: 67-77)). No significant difference in survival was observed between patients with strongly and weakly MDM2-positive tumours (P=0.3). Accordingly, in the independent validation series weak and strong MDM2 positivity were combined and considered to be MDM2 positive. MDM2 expression was seen in 230/1747 (13%) interpretable cases in this series, with a significant difference (P<0.0001) in DSS between MDM2-negative and MDM2-positive cases (10 year DSS 58% (95% CI: 51-64) vs 73% (95% CI: 70-75)). MDM2 was an independent prognostic marker (HR=1.35, P=0.02) in a Cox regression model including MDM2 expression, tumour grade, nodal status, ER status and tumour size. Immunohistochemical studies of MDM2 in more than 2000 breast carcinomas show that MDM2 is an independent negative prognostic marker.

Biomarkers, Tumor↗

PubMed2006

Cyclin D1 protein overexpression and CCND1 amplification in breast carcinomas: an immunohistochemical and chromogenic in situ hybridisation analysis.

Conflicting results on the prevalence of cyclin D1 ovexpression and its correlation with CCND1 amplification and outcome of breast cancer patients have been reported. Owing to limited sensitivity and specificity of most antibodies against cyclin D1, evaluation of cyclin D1 immunoexpression is reported to be problematic. The aims of this study were to assess the prevalence of cyclin D1 expression in breast carcinomas using the SP4 rabbit monoclonal antibody; to correlate cyclin D1 expression with amplification, assessed using chromogenic in situ hybridisation (CISH); and to analyse the relationship between CCND1 amplification and overexpression with clinicopathological parameters and outcome in a tissue microarray containing replicate tumour samples from 245 breast cancer patients. Immunohistochemistry for cyclin D1 was performed using the SP4 and the results were scored according to the Allred scoring system. CISH was carried out using the Zymed CCND1 SpotLight probe. CISH signals were counted in 60 morphologically unequivocal neoplastic cells. Amplification was defined as >5 signals per nucleus in more than 50% of cancer cells, or when large gene copy clusters were seen. Strong cyclin D1 expression and CCND1 amplification were found in 67.4 and 14.5% of the cases, respectively. A strong correlation between cyclin D1 overexpression and CCND1 amplification was demonstrated (P<0.0001). Cyclin D1 expression showed a positive correlation with hormone receptor expression (both ER and PgR, P<0.0001). An inverse correlation was observed between an immunohistochemical panel of 'basal-like' markers and both cyclin D1 overexpression (P<0.0001) and CCND1 amplification (P<0.0001). On univariate analysis cyclin D1 expression showed a correlation with longer overall survival (OS). Neither cyclin D1 nor CCND1 were independent prognostic factors for disease-free survival or OS. The results of this study confirm the association between cyclin D1 overexpression and positivity for hormone receptors and the lack of CCND1 amplification in basal-like breast carcinomas.

Antibodies, Monoclonal↗

PubMed2006

Expression profiles associated with aggressive behavior in Merkel cell carcinoma.

Primary neuroendocrine carcinoma of the skin, or Merkel cell carcinoma, is the most aggressive cutaneous neoplasm. In spite of its similarities to small cell carcinomas from other locations, Merkel cell carcinoma shows many peculiarities probably related to its epidermal origin and the etiologic role of UV radiation. We have immunohistochemically investigated 43 markers on a tissue microarray in which 31 surgically resected Merkel cell carcinomas were represented. Of these, 15 patients remained free of disease after removal, whereas 16 developed metastases. Immunoreactivity was scored according to staining intensity and the percentage of positive cells. We found statistically significant correlations between metastatic tumor spread and overexpression of matrix metalloproteinase (MMP) 7, MMP10/2, tissue inhibitor of metalloproteinase 3, vascular endothelial growth factor (VEGF), P38, stromal NF-kappaB, and synaptophysin. Also detected were statistically significant correlations between the expression levels of MMP7 and VEGF, MMP7 and P21, MMP7 and P38, MMP10/2 and VEGF, P38 and synaptophysin, P38 and P53, and P21 and stromal NF-kappaB. These findings may be helpful in predicting the clinical course of Merkel cell carcinoma and are potentially useful for the development of targeted therapies.

Biomarkers, Tumor↗

PubMed2004

Application of tissue microarray: evaluation of the expression of S-100-positive dendritic cells, tumor suppressor gene p63 and tissue inhibitor of metalloproteinase-1 in laryngeal carcinoma.

OBJECTIVE: To evaluate the predictive role of S100-positive dendritic cells, tissue inhibitor of metalloproteinase-1 (TIMP1) and p63 gene in laryngeal carcinoma using a tissue chip. MATERIAL AND METHODS: The expression of dendritic cells, TIMP1 and p63 gene in a series of 85 primary laryngeal carcinoma patients who had undergone operations in our hospital between 1992 and 2000 was studied immunohistochemically using the streptavidin-biotin peroxidase-conjugated method. RESULTS: Some cases were lost or showed no tumor tissue in the tissue chip. The rate of expression of dendritic cells was 59.5% and there were significant differences in expression between the differential degrees of laryngeal squamous carcinoma and the different clinical stages (p <0.05). The basal membrane and extracellular matrix of the specimens were strongly stained by TIMP1 in 55.7% of cases. There were statistically significant correlations between TIMP1 protein expression and early- and advanced-stage tumors, lymph node metastasis and 3-year survival rate (p <0.05). No statistically significant correlations were found between p63 protein expression and any of the clinical parameters. CONCLUSIONS: The tissue microarray technique used in this study is quick, inexpensive and very consistent. It is suggested that TIMP1 and S100 should be used as clinical discriminators of laryngeal carcinoma.

Adult↗

PubMed2006

Human postmortem brain tissue and 2-mm tissue microarrays.

The authors constructed tissue microarray (TMA) blocks from human postmortem brain including numerous core samples measuring 2 mm in diameter from various anatomic regions. These TMA sections were then processed using various stainings and pretreatment techniques to evaluate their properties. The loss of core samples ranged from 2% to 100% and was significantly influenced by the type of glass slide used; it was lowest (2-8%) with SuperFrost Plus slides. The losses were not significantly altered when applying the most demanding pretreatment procedures or using human brain tissue with a long postmortem delay. A slight influence on the quality and the repeatability of some of the IHC stainings was seen by the postmortem delay, by the brain region, or by the glass slide used. One special feature of the constructed brain TMA block including many anatomic brain regions is that persons who lack skills in neuroanatomy can identify various brain structures simply by following the x-y coordinates. Thus, the applications of this brain TMA block in neurologic research by scientists with different skill bases remain to be determined.

Autopsy↗

PubMed2005

Replicative MCM7 protein as a proliferation marker in endometrial carcinoma: a tissue microarray and clinicopathological analysis.

AIMS: To assess, in tissue microarray (TMA), the proliferative activity of endometrial carcinoma using one of the minichromosome maintenance (MCM) proteins (MCM7), and to explore its potential value for prognosis. MCM proteins are essential for eukaryotic DNA replication and have recently been used to define the proliferative compartments in human tissues. METHODS AND RESULTS: Immunohistochemistry for MCM7 and Ki67 was performed on TMAs constructed from 212 cases of endometrial carcinoma. MCM7 and Ki67 expression was quantified according to the extent of nuclear staining. An analysis was carried out of the association between MCM7 expression and that of Ki67 and the clinicopathological characteristics of endometrial carcinoma. MCM7 and Ki67 immunoreactivity was clearly evident in the nuclei of tumour cells. MCM7 and Ki67 labelling indices in endometrial carcinomas correlated with each other (P < 0.001). A significant correlation existed between the MCM7 labelling index and histological grade (P = 0.008) and patients' age at diagnosis (P < 0.001). Well-differentiated carcinomas and younger patients had a lower MCM7 index. Poor survival was observed in patients with endometrial carcinoma with a high MCM7 index (P = 0.03) and MCM7 was found to be an independent prognostic factor by multivariate analysis (P = 0.04). The Ki67 labelling index correlated with histological grade (P = 0.01) but had no significant prognostic impact (P = 0.50). CONCLUSIONS: In this TMA study on endometrial carcinoma, MCM7 was found to be a more reliable and useful marker than Ki67 in assessing tumour proliferation and in the prognosis of patients.

Adolescent↗

PubMed2006

HER-2/neu gene amplification in ovarian tumours: a comprehensive immunohistochemical and FISH analysis on tissue microarrays.

AIMS: Data on HER-2/neu overexpression, its correlation to prognosis and the success of treatment with Herceptin((R)) in ovarian carcinomas are scarce and contradictory. Therefore we assessed HER-2/neu expression and amplification in a large series of ovarian tumours by using tissue microarrays (TMAs). METHODS AND RESULTS: Two TMAs containing 173 invasive carcinomas, 36 borderline tumours, 20 granulosa cell tumours, 14 carcinosarcomas, 11 benign cystadenoms and eight other pelvic tumours were constructed to assess HER-2/neu gene amplification by fluorescence in-situ hybridization (FISH) and immunohistochemistry. Immunohistochemistry was successful in 94.3%; 81.8% were HercepTest negative, 11.3% were scored as 1+, 4.1% as 2+ and 2.8% as 3+, including 3.1% of invasive carcinomas, 2.8% of borderline tumours and 7.7% of carcinosarcomas; 83.6% could be analysed successfully by FISH revealing no aberration in 75.8%, low amplification in 2.7% and high amplification in 3.7% of the cases. In 17.8% monosomy, trisomy, polysomy or deletion could be detected. All cases with high-level amplification had 2+ or 3+ scores on immunohistochemistry. CONCLUSIONS: TMA is a feasible tool to study a large number of ovarian cases. Correlation between immunohistochemistry and FISH was excellent. HER-2/neu overexpression or gene amplification does not correlate with histological tumour type, stage, grade or prognosis.

Adolescent↗

PubMed2004

Ezrin expression in tissue microarray of primary and recurrent gliomas.

Malignant progression, infiltrative growth pattern and recurrencies after surgery are characteristic features of diffuse gliomas. Ezrin is a membrane-cytoskeleton linker protein expressed in several types of neoplasms. In experimental models, increased ezrin expression correlates with invasion of malignant glioma cells. We studied ezrin expression and its correlation with patient survival in 229 primary and recurrent astrocytomas (WHO grades II-IV), oligodendrogliomas (II-III) and oligoastrocytomas (II-III) of 113 patients. Ezrin expression as evaluated by immunohistochemistry and immunoblotting was detected in all studied glioma types. Staining intensity and number of immunoreactive cells correlated with increasing malignancy of astrocytomas and oligoastrocytomas (P = 0.001). Ezrin expression was strongest in astrocytomas (P = 0.006). Also oligodendrogliomas were positive for ezrin. High ezrin expression in primary gliomas correlated with shorter time to recurrence (P < 0.05) and poor overall survival (P < 0.05) of the patients. Ezrin expression increased during progression of the tumours (P < 0.05). However, ezrin was not an independent prognostic factor. The results of this study show that ezrin expression is associated with progression of gliomas and correlates with histological cell type and WHO tumour grade.

Adolescent↗

PubMed2006

Vimentin and laminin expression is associated with basal-like phenotype in both sporadic and BRCA1-associated breast carcinomas.

AIMS: To determine whether basal-like phenotype and vimentin and/or laminin are related in both sporadic/familial (BRCA1 or BRCA2 mutated) tumours. METHODS: 230 non-familial and 28 hereditary node-negative invasive breast carcinomas were immunohistochemically analysed for oestrogen receptors (ER), progesterone receptors (PR), cytokeratin 5/6 (CK5/6), epidermal growth factor receptors (EGFR), Ki67, p53, vimentin and laminin, using tissue microarrays. Tumours were considered to have basal-like phenotype if they were ER negative and HER2 negative, but positive for CK5/6 and/or EGFR. RESULTS: In sporadic tumours, vimentin expression was found in 77.8% cases with basal-like phenotype and 15.5% of non-basal cases (p<0.001). In familial cases, vimentin was expressed in 83.3% basal-like cancers and 16.7% of non-basal tumours (p<0.001). Vimentin expression was more frequent in BRCA1 than BRCA2 mutation carriers. Vimentin expressing tumours were associated with poor prognosis (p = 0.012) among patients not receiving adjuvant chemotherapy and showed a trend for local recurrence or visceral but not bone metastasis (p = 0.021). Laminin expression was also related to basal-like phenotype in both sporadic/familial cases (p<0.001 and p = 0.007, respectively), but neither with prognosis nor recurrence pattern in sporadic cancers. CONCLUSIONS: Vimentin and laminin expression is associated with basal-like phenotype in breast cancer. Expression of vimentin and laminin is characteristic of BRCA1 associated tumours. Since vimentin and laminin staining is widely used by pathologists for diagnostic purposes, thus demonstrating the robustness of their specific antibodies, the immunohistochemical evaluation of these two molecules could be used in identification of basal-like breast tumours in both sporadic/familial cases.

Biomarkers, Tumor↗