Proteins from the Wnt pathway are involved in the pathogenesis and progression of mammary phyllodes tumours.

BACKGROUND: The Wnt pathway is important in cell signalling transduction and is involved in the pathogenesis of multiple tumour types. A comprehensive analysis of the expression of Wnt signalling pathway proteins in mammary phyllodes tumours (PTs) has not been previously performed. AIMS: To evaluate the immunohistochemical expression of Wnt pathway proteins in a cohort of PTs, to determine their role in tumour pathogenesis and to identify any associations with patient outcome. METHODS: 65 PTs (34 benign, 23 borderline and 8 malignant) diagnosed at a single institution between 1990 and 2006 were analysed. Immunohistochemical stains were performed on tissue microarrays for beta-catenin, Wnt1, Wnt5a, SFRP4 and E-cadherin. Stroma and epithelium were scored separately. RESULTS: Stromal cytoplasmic Wnt5a and SFRP4 expression showed significant progressive increases in expression with increasing grade (p = 0.002 and p = 0.02 respectively). Epithelial membranous and stromal nuclear beta-catenin, epithelial cytoplasmic Wnt1 and epithelial E-cadherin all also showed increasing expression with increasing tumour grade, however, the differences were not significant. Disease-free survival was significantly decreased (p = 0.0017) with positive epithelial E-cadherin staining. CONCLUSIONS: Results suggest that alterations in the Wnt pathway are important in the progression and in the epithelial and stromal interactions in PTs. They have important implications for understanding the pathogenesis of these uncommon but clinically important tumours.

Phyllodes tumours of the breast: a clinicopathological analysis of 65 cases from a single institution.

The aim of this study was to document the clinical and pathological features of a large single institutional series of ethnically diverse patients with phyllodes tumours (PTs), and to determine which characteristics were predictive of outcome. Sixty five PTs were analysed; 34 were benign, 23 borderline and eight malignant (34 low grade and 31 high grade PTs on a two tiered grading system). Nine patients (15%) had local recurrences. A greater percentage of higher grade tumours recurred and women of Asian origin had a higher recurrence rate compared to the non-Asian patients. The 5 year disease-free survival was 81% and time to recurrence was significantly lower in the high grade group. No metastases or deaths from disease were recorded. The mean age at diagnosis significantly increased with tumour grade. The mean tumour volume also significantly increased with grade. Tumour grade was the only parameter related significantly to outcome.

The advantage of using a synoptic pathology report format for cutaneous melanoma.

AIMS: Although the synoptic format is being increasingly used for primary cutaneous melanoma pathology reporting, no study assessing its value has yet been reported in the literature. The aim was to determine whether the use of synoptic reports increases the frequency with which pathological features that may influence prognosis and guide management are documented. METHODS AND RESULTS: Melanoma pathology reports (n = 1692) were evaluated; 904 were in a synoptic format [671 Sydney Melanoma Unit (SMU) reports and 233 non-SMU reports] and 788 were non-synoptic (184 SMU reports and 604 non-SMU reports). Reports (n = 1354) from 677 patients who had both a SMU report and a non-SMU report were compared. Almost all features were reported more frequently in synoptic than in non-synoptic reports (P < 0.001). No significant differences were found in the frequency of reporting the main pathological features between SMU and non-SMU synoptic reports. Synoptic reports were more frequently used by SMU (78%) than by non-SMU pathologists (28%). CONCLUSIONS: This is the first study to provide objective evidence that synoptic pathology reports for melanoma are more complete than non-synoptic reports (regardless of whether the reports are generated within or outside a specialist melanoma centre). All synoptic reports should include the facility for free text, be tailored to individual institutional requirements and be updated regularly to be of maximal value.

Surgical biopsy with intra-operative frozen section. An accurate and cost-effective method for diagnosis of musculoskeletal sarcomas.

The most appropriate protocol for the biopsy of musculoskeletal tumours is controversial, with some authors advocating CT-guided core biopsy. At our hospital the initial biopsies of most musculoskeletal tumours has been by operative core biopsy with evaluation by frozen section which determines whether diagnostic tissue has been obtained and, if possible, gives the definitive diagnosis. In order to determine the accuracy and cost-effectiveness of this protocol we have undertaken a retrospective audit of biopsies of musculoskeletal tumours performed over a period of two years. A total of 104 patients had biopsies according to this regime. All gave the diagnosis apart from one minor error which did not alter the management of the patient. There was no requirement for re-biopsy. This protocol was more labour-intensive and 38% more costly than CT-guided core biopsy (AU$1804 vs AU$1308). However, the accuracy and avoidance of the anxiety associated with repeat biopsy outweighed these disadvantages.

Stromal nitric oxide synthase (NOS) expression correlates with the grade of mammary phyllodes tumour.

BACKGROUND: Nitric oxide synthase (NOS), particularly endothelial and inducible forms (e/i-NOS), are expressed in various cancers, including breast cancer. In mammary fibroepithelial lesions, NOS expression in stromal cells has been reported to be lower in fibroadenomas than in phyllodes tumours. AIMS: To investigate NOS expression in phyllodes tumours of varying degrees of malignancy. METHODS: One hundred and sixty seven mammary phyllodes tumours (97 benign, 47 borderline malignant, and 23 frankly malignant) were evaluated for e-NOS and i-NOS expression by immunohistochemistry. Correlations with previously reported expression of stromal vascular growth factor (VEGF) and microvessel density were also performed. RESULTS: Stromal expression of e-NOS was absent, weak, moderate, and strong in 43%, 31%, 13%, and 13% of benign tumours; 17%, 26%, 13%, and 44% of borderline malignant tumours; and 17%, 35%, 13%, and 35% of frankly malignant tumours, respectively. Stromal expression of i-NOS was 77%, 18%, 4%, and 1% in benign tumours; 42%, 28%, 19%, and 11% in borderline malignant tumours; and 43%, 13%, 26%, and 18% in frankly malignant tumours, respectively. Stromal expression of both i-NOS and e-NOS was significantly different between the benign and malignant (borderline and frank) groups of phyllodes tumours (p < 0.0001). Furthermore, the expression of i-NOS correlated with stromal VEGF expression and microvessel density. The expression of NOS in the epithelial cells was strong, and showed no differences between the different groups of tumours. CONCLUSIONS: Higher stromal expression of NOS in phyllodes tumours is associated with malignancy, suggesting a possible role in malignant progression, particularly metastasising potential.

Stromal CD10 expression in mammary fibroadenomas and phyllodes tumours.

BACKGROUND/AIMS: CD10 (CALLA) has recently been reported to be expressed in spindle cell neoplasia, and has been used to differentiate endometrial stromal sarcoma from leiomyoma and leiomyosarcoma. In the breast, myoepithelial cells express CD10, but there are few studies of the expression of CD10 in mammary fibroepithelial lesions. METHODS: Stromal CD10 expression was studied in 181 mammary phyllodes tumours (102 benign, 51 borderline malignant, and 28 frankly malignant) and 33 fibroadenomas using immunohistochemistry, to evaluate whether differences in expression correlated with the degree of malignancy. RESULTS: There was a progressive increase in the patients' age and tumour size, from fibroadenoma to phyllodes tumours with an increasing degree of malignancy (p < 0.001). Stromal CD10 expression was positive in one of 33 fibroadenomas, six of 102 benign phyllodes tumours, 16 of 51 borderline malignant phyllodes tumours, and 14 of 28 frankly malignant phyllodes tumours. The difference was significant (p < 0.001) and an increasing trend was established. Strong staining was seen in subepithelial areas with higher stromal cellularity and activity. Stromal CD10 expression had a high specificity (95%) for differentiating between benign lesions (fibroadenomas and benign phyllodes tumours) and malignant (borderline and frankly malignant) phyllodes tumours. CONCLUSIONS: CD10 may be a useful adjunct in assessing malignancy in mammary fibroepithelial lesions.