Borderline Phyllodes Tumors Research Articles

Giant Borderline Phyllodes Breast Tumor in Pregnancy

INTRODUCTION: Phyllodes is a rare breast tumor that grows rapidly and to a large size, being exceedingly rare during pregnancy. These tumors may be classified as benign, borderline or malignant. Up until now there is no report in the literature of a borderline phyllodes arising during pregnancy. CASE REPORT: a 29 years old white female patient at the 15th week of pregnancy presented with a large mass in left breast that have been growing for 6 months. The patient had a previous history of osteossarcoma in the left jaw five years before. At physical exam there was a protruding and hardened palpable mass occupying the whole left breast. There were no signs of cutaneous involvement or axillary lymphadenomegaly. In the right breast there were two palpable mobile tumors. She did not had a mammogram because of the size of the tumor. Ultrasound showed four nodules in the right breast. The largest one measured 5 cm in diameter. In the left breast there were confluent masses with well-defined margins, with heterogeneous echotexture, cystic areas and posterior acoustic enhancement. Ultrasound-guided percutaneous biopsy was performed in both breasts. The correspondent histophatological examination revealed a biphasic fibroepithelial lesions with atypical stromal component that were classified as borderline lesions. After these results, patient underwent mas¬tectomy without axillary dissection on the left side and tumorectomy on the right breast. Anatomopathologic analysis of the surgical specimen of left breast revealed a 20x10 cm necrotic tumor. In the right breast three rounded nodules were found. All lesions were classified as borderline phyllodes tumors. Surgical margins were free of tumor. DISCUSSION: Phyllodes are extremely rare during pregnancy. There are only eight cases reported to this date, all classified as malignant. To the best of our knowledge, we report here the first case of a borderline phyllodes occurring in pregnancy. It is unknown if these tumors are hormone dependent. The aim of treatment is to perform a wide resection with free margins. The adjuvant treatment for borderline phyllodes tumors is not yet defined.

Stromal Matrix Metalloproteinase-14 Expression Correlates With the Grade and Biological Behavior of Mammary Phyllodes Tumors

Phyllodes tumors (PTs) of the breast are rare biphasic tumors with the potential for invasion and metastatic spread. Matrix metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs) are involved in several key aspects of tumoral growth, invasion, and metastasis, but little is known of their expression in PTs. The objective of this study was to assess the expression of MMPs and TIMPs in PTs and to determine their association with grade and clinical behavior of PTs. Eighty-two PTs (50 benign, 22 borderline, and 10 malignant) were studied. Automated immunohistochemical staining for MMP-1, -2, -7, -9, -11, -13, and -14 and TIMP-1, -2, and -3 was performed using tissue microarray blocks and the expression of MMPs and TIMPs was assessed in the stromal component. There were no significant differences in the expression of stromal MMPs and TIMPs in the 3 groups of PTs, except for MMP-14. There was a significant increase in stromal MMP-14 expression with increasing PT grade (P<0.01). The stromal MMP-14 expression in the borderline and malignant PTs was higher than that in benign PTs (P<0.05 and P<0.05, respectively). Furthermore, the expression of stromal MMP-14 was associated with a higher rate of recurrence (P<0.05). Our results show for the first time that stromal MMP-14 expression is associated with the grade and clinical behavior of PTs of the breast.

Recurrent Giant Phyllodes Tumour of the Breast Pathological Considerations and Management Approach for Recurrence and Metastasis

Phyllodes tumours are rare and account for 0.4% of all breast tumours. The majority of them tend to be less than 5 cms in size with giant tumours larger than 10 cms being about 20% of these cases. They display a broad range of clinical and pathological behavior and are regarded as falling within the spectrum of fibroepithelial neoplasms. Surgery has been the primary modality of treatment. However the extent of resection and the role of adjuvant radiotherapy and chemotherapy are still controversial. The risk of recurrence is (4.7% - 30%) for benign phyllodes tumour and (30% - 65%) for borderline and malignant phyllodes tumour. A case of giant phyllodes tumour measuring 36 × 30 cm and weighing 6.8 kg is presented, which had recurred following a previous resection 5 years back. The literature is reviewed with regards to pathology, the role of investigations, nature of resection and the risk factors for recurrence and metastasis

The sensitivity of needle core biopsy in combination with other investigations for the diagnosis of phyllodes tumours of the breast

BackgroundThe sensitivity of needle-core biopsy (NCB) in diagnosing phyllodes tumours has only been addressed by a handful of small studies. The aim of this study was to analyse the sensitivity of NCB in the diagnosis of phyllodes tumours and to compare this to the sensitivity of other commonly performed investigations. A secondary aim was to assess the effect of various patient and disease factors on the rate of false negative test results. MethodsPathology databases were interrogated to identify all patients with the SNOMED term M-9020 or the word phyllodes in specimen reports. Excisional specimen reports were matched to prior FNAC reports, NCB reports and imaging reports. ResultsNinety-one patients had a confirmed phyllodes tumour on excision. The sensitivity of FNAC, NCB and imaging for diagnosing phyllodes tumours was 40%, 63% and 65% respectively. The sensitivity of imaging and NCB was greater for borderline and malignant lesions. Combining cytohistological and radiological tests improved sensitivity to 76%. A younger age was associated with a greater false negative rate for all tests. Borderline and malignant phyllodes tumours were significantly associated with advancing age and greater lesion size on imaging and histology. ConclusionsThis is the largest report to date assessing the sensitivity of NCB in the diagnosis of phyllodes tumours. Increased sensitivity in the diagnosis of phyllodes tumours can be achieved by combining cytohistological and radiological test results. The novel association between younger age and false negative results warrants further investigation. The most likely explanation is a reluctance to diagnose phyllodes tumours in young women given the increased prevalence of cellular fibroadenomas in this age group.

486 From the 1 Department of Pathology, Faculty of Medicine, University Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia, 2 Department of Surgery, Faculty of Medicine, University Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia, 3 Department of Anatomy, Faculty of Medicine, University Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia Received: Jan. 18, 2011; Accept: Mar. 8, 2012 Correspondence to: Dr. Siti

Fibroadenomas (FA) are common while phyllodes tumors (PT) are rare and both tumors are composed of epithelial and stromal components. We evaluated the expression status of ER, Bc12, p53, and MIB-1 protein in these tumors. One hundred and ninety-three tumors comprising of 117 FAs and 76 PTs were examined using immunohistochemistry on tissue microarray. The mean age of patients with FA was 28.5 years while the mean ages of patients with benign, borderline and malignant PTs were 41.7, 48.6 and 42.1 years, respectively. Also all types of PTs were large (>Scm). ER showed a strong nuclear staining in the epithelial component of all tumors while ER/3 immunoreactivity was detected in both the epithelial and stromal components ofF A and PT. ER/β (p<0.001), and p53 (p=0.006) in the stromal component were associated with tumor size. p53 expression was significantly associated with both the epithelial and stromal components of malignant PTs (p<0.05). In the PT, the decreased expressions of p53 and MIB-1 were significantly different with positive Bc12 protein expression in the epithelial component (p=0.000). In addition, MIB-1 was also found to be associated with ER and ER/3 in the stromal component (p=0.000). The expression of p53 with tumor size and histological grade in PT may increase the risk for malignancy.

Significance of epidermal growth factor receptor expression in the grading of phyllodes tumors of the breast

Background and aim: Limited studies on the relationships between epidermal growth factor receptor (EGFR) expression and the grades of phyllodes tumors (PT) of the breast were reported. This study evaluated the significance of EGFR overexpression in the grading of PT. Methods: Immunohistochemical stain for EGFR was done in 46 PT cases. The differences of EGFR expression according to the degrees of cytologic atypia and mitotic count and between benign, borderline and malignant PTs based on Rosen or World Health Organization (WHO) criteria were analyzed. Results: Significant differences of positive (moderate membranous and cytoplasmic, more than 10% of tumor cells) and strong positive (moderate more than 50% of tumor cells) reactions for EGFR were found according to the degree of cytologic atypia (P= 0.0016 and P= 0.0122) and between the PTs showing ≤5 mitoses and >5 mitoses/10 high power field (P= 0.0230 and P= 0.0058). Positive reaction for EGFR was more common in borderline/malignant PTs than benign PTs, and strong positive reaction for EGFR was relatively common in malignant PTs. Conclusions: Epidermal growth factor receptor overexpression, more than 10% of tumor cells, could be used as an ancillary tool for the discrimination of benign from borderline and malignant PTs.

Mastectomía por fibroadenoma gigante juvenil recidivante

Fibroadenomas are the most common breast lesions in adolescents. The term “giant fibroadenoma” is used when the tumor reaches a size of more than 5 cm or weighs more than 500 g. Treatment consists of tumorectomy or, in a very few cases, mastectomy. The histological differential diagnosis between fibroadenoma and phyllodes tumor, a highly recurrent and usually benign lesion, is sometimes difficult. We present the case of a 17-year-old patient diagnosed with a giant fibroadenoma, who underwent five interventions due to multiple tumoral recurrences, with the final result of a mastectomy. The lesion was twice diagnosed as a borderline phyllodes tumor. The interest of this case lies in its exceptional clinical course. This case also illustrates the difficulty of surgical indication in some benign breast lesions with difficult histological diagnosis.

Largest Phyllodes Tumor- Case Report and Brief Review Article

This is an article reporting the largest phyllodes tumor and the role of radiotherapy in patients of phyllodes tumor of breast, based on Medline search for articles in English language using keywords "role of radiotherapy in phyllodes tumor of breast". 32years female presented with a lump in right breast since last 4months. This was the second recurrence of similar lump in last 6years. Biopsy from the lump proved to be cystosarcoma phyllodes. Radical Mastectomy with level I node sampling and reconstruction with Latissimus Dorsi Myocutaneous flap was done as a curative procedure. The tumor measured exactly to be 50 × 25.2 × 16.4cm in size and 15kg in weight. Proliferation markers like Ki- 67 and p53 were in the range of 1-2% and 3-4% respectively. Histopathological diagnosis of the tumor was borderline phyllodes tumor. Patient had an uneventful postoperative course and is presently on three monthly follow up since 1year.

Imaging findings in phyllodes tumors of the breast

To study the radiological appearance and pathological features of breast phyllodes tumors (PTs), and to enhance the recognition of the tumor. Clinical and imaging findings were retrospectively reviewed in 24 women with PTs confirmed by surgical pathology. All of the 24 patients had preoperative MRI and sonography, and 10 had preoperative mammography. The histologic findings were benign, borderline and malignant PTs in 16.7% (4/24), 45.8% (11/24) and 37.5% (9/24) of cases, respectively. The tumor size (p=0.001), irregular shape on sonographic imaging (p=0.039), internal non-enhanced septations (p=0.009), silt-like changes in enhanced images (p=0.006) and signal changes from T2-weighted to enhanced images on MRI (p=0.001) correlated significantly with the histologic grade; the BI-RADS category of the MRI could reflect the PT's histologic grade with a correlation coefficient of 0.440 (p=0.031). If the category BI-RADS ≥4a was considered to be a suspicious malignant lesion, the diagnostic accuracy of mammography, US and MRI would be 70% (7/10), 62.5% (15/24) and 95.8% (23/24), respectively. The tumor size and several US and MRI findings can be used to help preoperatively determine the histologic grade of breast PTs. When a patient presents with a progressively enlarging, painless breast mass, MRI should be recommended first.

Phyllodes Tumor in a 16-Year-Old Girl

Phyllodes tumors occur with a frequency of 0.3% to 0.9% and are rare neoplasm, particularly in adolescent girls and young women [1]. We report a 16-year-old girl diagnosed with borderline phyllodes tumor. A painless mass in upper part of the right breast had begun to occur approximately 2 years ago in a 16-year-old girl. Approximately 3 months ago, rapid growth of the mass and pain in the right breast had occurred. The patient appealed to a general surgeon with these complaints. On the physical examination, a firm mass sized 8 × 3c m in the upper part of the right breast was palpated. Ultrasonography (USG) revealed a mass lesion showing lobulation and heterogenic hypoechoic internal echogenicity but not calcification. That mass was totally excised with surrounding intact tissue. The patient diagnosed with phyllodes tumor by pathologic examination was referred to our hospital. On the physical examination, there was an incision scar in the upper part of the right breast owing to the surgery performed. No mass lesion was found in both breasts. All lymph node regions, particularly bilateral axillary regions, were normal. Examination of other systems was normal. Complete blood count and biochemical parameters were in normal ranges. Histopathologic examination of the pathology slides revealed mitosis number 6, moderate stromal cellularity, and moderate atypia among stromal cells (Figure 1). Surgical margins were intact. With these findings, the patient was histopathologically diagnosed with “borderline phyllodes tumor.” No additional pathologies were found on thorax tomography of the patient. Since it was borderline phyllodes tumor and surgical margins were intact, surgical process performed was accepted to be adequate and the patient was put under follow-up. Phyllodes tumor is rare and most commonly occurs between the ages of 35 and 55. Usually it is unilateral; it rarely occurs bilaterally as isolated mass. Patients generally appeal with the complaint of sudden enlargement of a mass existing for a long time, as did in our patient [1]. Phyllodes tumor is rare among adolescents. In this age group, fibroadenoma and phyllodes tumor are two well-confined lesions of breast. Both of them similarly include epithelial and stromal components. However, clinical courses of them differ. Fibroadenomas grow slowly and usually their growth stops after a maximum size of 2 to 3 cm. Moreover, in a part of the patients, fibroadenomas regress to a

Management of Phyllodes Breast Tumors

Phyllodes tumors are a rare distinctive fibroepithelial tumors of the breast and their management continues to be questioned. The aim of our study was to examine the treatment and outcome of 165 patients with phyllodes tumors and to review the options for surgical management. This is a retrospective study of 165 patients who presented to the Institut Curie between January 1994 and November 2008 for benign, borderline or malignant phyllodes tumors. The median follow-up was 12.65 months [range 0-149.8]. The median age at diagnosis was 44 years [range 17-79]. One hundred and sixty patients (97%) had breast-conserving treatment, of whom 3 patients (1.8%) had oncoplastic breast surgery. Younger women had a significantly higher chance of having a benign phyllodes tumor (p = 0.0001) or a tumor of small size (p < 0.0001). Histologic examination showed 114 benign (69%), 37 borderline (22%) and 14 malignant tumors (9%). The median tumor size was 30 mm [range 5-150]. The tumor margins were considered incomplete (< 10 mm) in 46 out of 165 cases (28%) with 52% revision surgery. Only the tumor grade was a significant risk factor for incomplete tumor margins (p = 0.005). Fifteen patients developed local recurrence (10%) and two, metastases. In univariate analysis, the histologic grade (p = 0.008), and tumor size (p = 0.02) were significative risk factors for local recurrence with an accentuated risk for "borderline" tumors and tumors of large size.).Similar results were obtained using multivariate analysis (p = 0.07). The mainstay of treatment for phyllodes tumors remains excision with a safe surgical margin, taking advantage breast conserving surgery where amenable. For borderline or malignant phyllodes tumors or in cases of local tumor recurrence, mastectomy, and immediate breast reconstruction may become the preferred option. Genetic analysis will potentially supplement classical histologic examination in order to improve our management of these tumors. The role of adjuvant treatments is unproven and must be considered on a case-by-case basis.

Comparison of stromal CD10 expression in benign, borderline, and malignant phyllodes tumors among Egyptian female patients

Phyllodes tumors are group of biphasic fibroepithelial tumors of the breast of varying malignant potential, ranging from benign tumors to fully malignant sarcomas. According to the Egyptian National Cancer Institute, female malignant cases showed appreciable increase in the recent time period for breast cancer with the malignant phyllodes tumors representing 0.41% of cases in the year 2003-2004. This is an immunohistochemical study to compare CD10 expression in benign, borderline, and malignant phyllodes tumors, in order to highlight its diagnostic and prognostic values. This study conducted 34 Egyptian female cases of phyllodes tumors of different grades to be studied histologically and immunohistochemically using antibodies against CD10. The Chi-square test was used to determine differences in CD10 expression between benign, borderline, and malignant tumors. One-way ANOVA test was used to determine whether the difference was significant. Significance was established at P<0.05. In the 24 cases of benign phyllodes tumors, only four cases (16.7%) showed positive CD10 reactivity. Three cases (60%) out of five borderline phyllodes tumors showed positive CD10 reactivity, while four (80%) out of five cases of malignant phyllodes tumors showed positive CD10 staining. From these highly significant results, we believe that there is a strong correlation between CD10 expression and tumor grade, which could be an important observation that may have both diagnostic and prognostic implications as well as promising potential target for development of novel therapies.

Abstract P5-14-12: Management of Phyllodes Breast Tumours: A Review of 165 Cases

Abstract Aim:The aim of our study was to examine the treatment and outcome of 165 patients with phyllodes tumours and to review the options for surgical management. Patients and Methods: This is a retrospective study of 165 patients who presented to the Institut Curie between January 1994 and November 2008 for benign, borderline or malignant phyllodes tumours. Results: The median follow-up was 12.65 months [range 0 to 149.8]. The median age at diagnosis was 44 years [range 17 to 79]. One hundred and sixty patients (97%) had breast conserving treatment, of whom 3 patients (1. 8%) had oncoplastic breast surgery. Younger women had a significantly higher chance of having a benign phyllodes tumor (p = 0.0001) or a tumour of small size (&amp;lt; 0.0001). Histological examination showed 114 benign (69%), 37 borderline (22%) and 14 malignant tumours (9%). The median tumour size was 30 mm [range 5 to 150]. The tumour margins were considered incomplete (&amp;lt; 10 mm) in 46 out of 165 cases (28%) with 52% revision surgery. Only the tumour grade was a significant risk factor for incomplete tumour margins (p = 0.005). Fifteen patients developed local recurrence (10%) and two, metastases. In univariate analysis, the histological grade (p = 0.008) and tumour size (p=0.02) were significative risk factors for local recurrence with an accentuated risk for borderline tumours and tumours of large size. Similar results were obtained using multivariate analysis (p=0.07) Conclusion: The mainstay of treatment for phyllodes tumours remains excision with a safe surgical margin, taking advantage breast conserving surgery where amenable. For borderline or malignant phyllodes tumours or in cases of local tumour recurrence, mastectomy and immediate breast reconstruction may become the preferred option.Genetic analysis will potentially supplement classical histological examination in order to improve our management of these tumours. The role of adjuvant treatments is unproven and must be considered on a case-by-case basis. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-14-12.

CD34, CD117, and Ki-67 Expression in Phyllodes Tumor of the Breast: An Immunohistochemical Study of 33 Cases

Phyllodes tumors (PTs) of the breast are biphasic lesions, comprising an epithelial component set within a neoplastic spindle-celled stroma. These tumors have been classified as benign, borderline, and malignant based on a combination of histological criteria, including stromal cellularity, nuclear pleomorphism, mitotic rate, stromal overgrowth, and margin appearance. The aim of this study was to evaluate the expression of CD34, CD117 (c-kit), and Ki-67 in PT of the breast and attempt to correlate the staining pattern with tumor grade by morphology. Immunohistochemical expression of CD117, CD34, and Ki-67 was studied on formalin-fixed, paraffin-embedded archival tissue material from 33 cases of PT. Histologically, there were 21 benign, 6 borderline, and 6 malignant (high-grade) tumors. All 6 histologically malignant PTs were positive for CD117 (100%), but only 1 marked with CD34 (16.7%). Borderline PTs frequently coexpressed CD34 and CD117 (66.7%). The benign PTs, on the other hand, most commonly (52.4%) showed a CD34(+)/CD117(-) immunoprofile with 33.3% cases coexpressing the markers: that is, CD34(+)/CD117(+). Although most benign PTs (80.6%) showed a Ki-67 of <2%, a few cases showed slightly higher proliferation indices. This study indicates that CD34 and CD117 are differentially expressed in benign and malignant PTs. These markers, therefore, in combination, may be used as an adjunct to morphology in the subclassification of PTs.

Invasive Ductal Carcinoma Arising in Phyllodes Tumor With Isolated Tumor Cells in Sentinel Lymph Node

Phyllodes tumor (PT) consists of stroma of variable grading and benign ductal epithelium. Although exceptional, carcinomas that arise from the epithelium in PTs do exist, and seem to behave less aggressively than the usually encountered breast carcinoma. To the best of our knowledge, among the invasive carcinomas that have arisen in PTs, only 1 has been proved to have metastatic carcinoma in the lymph nodes. Here, we describe the youngest woman to have invasive ductal carcinoma that arose in a borderline PT, with isolated carcinoma cells in the sentinel lymph node. Whether such a combined lesion carries a more indolent course is also discussed.

Molecular classification of breast phyllodes tumors: validation of the histologic grading scheme and insights into malignant progression

Phyllodes tumors of the breast are rare fibroepithelial neoplasms with a potential for recurrence. Current histological classification is not always predictive of clinical behavior. The aim of this study was to identify genetic changes associated with the development of borderline and malignant phyllodes tumors in an Asian population, and to assess if genetic data supported the categorization of these tumors into the existing three grades of benign, borderline, and malignant. Expression profiling of 21 phyllodes tumors (6 benign, 10 borderline, 5 malignant) was performed using Affymetrix U133Plus 2.0 GeneChips(®). Gene expression among benign, borderline, and malignant tumors was compared and a 29 gene list was able to classify them according to their histologic grade. Among these 29 genes are those responsible for matrix formation, cell adhesion, epidermis formation, and cell proliferation. Comparative genomic microarray analysis showed that the most common chromosomal alteration associated with borderline and malignant tumors was 1q gain, and an increasing number of chromosomal changes was noted with increasing histological grade. Upregulation of HOXB13 was seen in malignant relative to borderline phyllodes tumors and further investigated by immunohistochemistry in a corresponding set of formalin-fixed, paraffin-embedded tumors. HOXB13 protein overexpression was found to be correlated with stromal hypercellularity and atypia (P=0.03, P=0.039, respectively) and may be implicated in the development of malignant phyllodes tumors.

Malignant Phyllodes Tumour with Liposarcomatous Differentiation, Invasive Tubular Carcinoma, and Ductal and Lobular Carcinoma In Situ: Case Report and Review of the Literature

A 43-year-old woman presented with a right breast lump that had enlarged over 5 months. She had chemoradiotherapy for non-Hodgkin's lymphoma in 1989. Histology revealed a malignant phyllodes tumour (PT) with liposarcomatous differentiation and ductal carcinoma in situ (DCIS) within the tumour with invasive tubular carcinoma, DCIS, and lobular carcinoma in situ in the surrounding breast. She had surgery and adjuvant radiotherapy. One year follow-up showed no recurrence or metastatic disease. Liposarcomatous differentiation is uncommon in PTs, and coexisting carcinoma is rare with 38 cases in 31 reports in the literature. Carcinoma is reported in malignant (n = 19), benign (n = 16) and in borderline PTs (n = 3) with invasive carcinoma (n = 18) and pure in situ carcinoma (n = 19) recorded in equal frequency. Carcinoma is more commonly found within the confines of benign PTs; whereas it is more often found surrounding the PT or in the contralateral breast in malignant PTs. Previous radiotherapy treatment is reported in only two cases. The aetiology of co-existing carcinoma is unclear but the rarity of previous radiotherapy treatment suggests that it is incidental. This case highlights the diverse pathology that can occur with PTs, which should be considered when evaluating pathology specimens as they may impact on patient management.

628 The microenvironment and the genome in breast cancer: how tissue architecture informs

Fibroepithelial tumors (FTs) of the breast are a heterogeneous group of lesions ranging from fibroadenomas (FAD) to phyllodes tumors (PT) (benign, borderline, malignant). Further understanding of their molecular features and classification might be of clinical value. In this study, we analysed the expression of 105 breast cancer-related genes, including the 50 genes of the PAM50 intrinsic subtype predictor and 12 genes of the Claudin-low subtype predictor, in a panel of 75 FTs (34 FADs, 5 juvenile FADs, 20 benign PTs, 5 borderline PTs and 11 malignant PTs) with clinical follow-up. In addition, we compared the expression profiles of FTs with those of 14 normal breast tissues and 49 primary invasive ductal carcinomas (IDCs). Our results revealed that the levels of expression of all breast cancer-related genes can discriminate the various groups of FTs, together with normal breast tissues and IDCs (False Discovery Rate < 5%). Among FTs, the levels expression of proliferation-related genes (e.g. CCNB1 and MKI67) and mesenchymal/epithelial-related (e.g. CLDN3 and EPCAM) genes were found to be most discriminative. As expected, FADs showed the highest and lowest expression of epithelial- and proliferation-related genes, respectively, whereas malignant PTs showed the opposite expression pattern. Interestingly, the overall profile of benign PTs was found more similar to FADs and normal breast tissues than the rest of tumours, including juvenile FADs. Within the dataset of IDCs and normal breast tissues, the vast majority of FADs, juvenile FADs, benign PTs and borderline PTs were identified as Normal-like by intrinsic breast cancer subtyping, whereas 7 (63.6%) and 3 (27.3%) malignant PTs were identified as Claudin-low and Basal-like, respectively. Finally, we observed that the previously described PAM50 risk of relapse prognostic score better predicted outcome in FTs than the morphological classification, even within PTs-only. Our results suggest that classification of FTs using gene expression-based data is feasible and might provide clinically useful biological and prognostic information.

Mutation-Free Expression of c-Kit and PDGFRA in Phyllodes Tumors of the Breast

Purpose: Phyllodes tumors (PTs) of the breast have been classified as benign, borderline, or malignant based on their histopathologic features. However, predicting clinical behavior based on these features has proven to be difficult given that local recurrence occurs in both benign and malignant PTs. Recurrence has been shown to mirror the histologic pattern of the primary tumor or to show dedifferentiation. The aim of this study was to assess the value of the histopathologic parameters, expression or mutation of c-Kit and platelet derived growth factor receptor alpha (PDGFRA) in predicting tumor recurrence. Methods: Representative areas from 39 benign, 16 borderline, and 12 malignant PTs were selected for construction of tissue microarrays. Immunohistochemical analyses for p53, Ki-67, c-Kit, and PDGFRA were performed and SSCP-PCR analysis was carried out to identify mutations in exons 9, 11, 13, and 17 of the c-Kit gene and exons 12 and 18 of the PDGFRA gene. Clinicopathologic features, including tumor recurrence and margin status, were also evaluated. Results: Of the 67 PTs, 11 cases (16.4%) recurred from 3 to 92 months following initial diagnosis (4 benign, 2 borderline, and 5 malignant). One benign PT case recurred as a borderline tumor and two borderline PT cases recurred as malignancies. Three patients died of malignant PT. No mutations of the c-Kit or PDGFRA genes were found and there was no statistically significant association of either p53 or p16 immunostaining with recurrent disease (p>0.05). However, histologic grade (p=0.033), margin status (p< 0.001), Ki-67 (p=0.012), c-Kit (p=0.002), and PDGFRA (p= 0.007) stromal immunopositivity were significantly correlated with recurrence. Conclusion: Even though positive or close margins were significantly associated with tumor recurrence, stromal c-Kit, PDGFRA positivity, and the Ki-67 index were useful for predicting recurrent PTs. Despite this, no c-Kit or PDGFRA mutations were found.

9. EGFR over expression, not amplification, is involved in the pathogenesis and progression of mammary phyllodes tumours

<h3>Aims</h3> To study the expression of EGFR and to assess for EGFR and HER2 amplifications in a cohort of patients with phyllodes tumours (PTs) from a single institution and to assess for correlations with PT grade and patient outcome. <h3>Methods</h3> 65 PTs from 62 patients diagnosed at a single institution between 1990 and 2006 were analysed. The PTs were subdivided into 3 grades (benign, borderline and malignant); and alternatively into 2 grades (all benign PTs were classified as low grade, and borderline and malignant tumours were combined into a high grade group). Immuno-histochemical (IHC) staining was performed on tissue micro-arrays for EGFR. Chromogenic and silver <i>in situ</i> hybridisation (CISH/SISH) were performed to assess for EGFR and HER2 gene amplifications, respectively. <h3>Results</h3> Stromal EGFR IHC expression was significantly higher in the high grade tumours compared to the low grade tumours on the 2 tiered grading scheme (<i>p</i>=0.03). On the 3 tiered grading scheme, stromal EGFR IHC was significantly different between the benign and malignant tumours (<i>p</i>=0.000006) and the borderline and malignant tumours (<i>p</i>=0.00007) but not between the benign and borderline tumours (<i>p</i>=0.7). No significant correlation was found between epithelial expression and PT grade, nor between epithelial or stromal expression and outcome. On EGFR CISH, one borderline PT had low amplification in the epithelium, and one malignant PT had low amplification in the stroma. No HER2 amplifications were seen on the SISH. <h3>Conclusion</h3> The results suggest a role for EGFR (but not HER2) in the pathogenesis of PTs. Overexpression of stromal EGFR is probably involved in the progression of PTs but by means other than amplification.